Oxidative Stress and Inflammation, 3rd Edition

Journal Name	Impact Factor	CiteScore	Launched Year	First Decision (median)	APC
Antioxidants antioxidants	8.2	14.7	2012	18.7 Days	CHF 2900	Submit
Biomedicines biomedicines	4.5	7.8	2013	18.2 Days	CHF 2600	Submit
Cosmetics cosmetics	4.1	6.0	2014	17 Days	CHF 1800	Submit
International Journal of Molecular Sciences ijms	5.6	10.0	2000	17.5 Days	CHF 2900	Submit
Life life	3.9	7.1	2011	15.3 Days	CHF 2600	Submit
Nutraceuticals nutraceuticals	-	4.4	2021	24.9 Days	CHF 1200	Submit
Oxygen oxygen	3.7	13.3	2021	24.6 Days	CHF 1200	Submit

13 pages, 2600 KB

Open AccessArticle

Effects of ATP and Taxifolin on Atezolizumab-Induced Renal Injury: A Biochemical, Histopathological, and Immunofluorescence Evaluation

by Adil Furkan Kilic, Esra Tuba Sezgin, Gulbaniz Huseynova, Cengiz Sarigul, Mustafa Ozkaraca, Ali Gungor, Renad Mammadov, Halis Suleyman and Orhan Cimen

Life 2026, 16(7), 1118; https://doi.org/10.3390/life16071118 - 5 Jul 2026

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Abstract

Background: Immune checkpoint inhibitors (ICIs), particularly programmed death-ligand 1 (PD-L1) inhibitors such as atezolizumab, have significantly improved outcomes in cancer therapy. However, these agents may cause immune-related adverse effects, including nephrotoxicity associated with oxidative stress and cellular stress responses. This study aimed to [...] Read more.

Background: Immune checkpoint inhibitors (ICIs), particularly programmed death-ligand 1 (PD-L1) inhibitors such as atezolizumab, have significantly improved outcomes in cancer therapy. However, these agents may cause immune-related adverse effects, including nephrotoxicity associated with oxidative stress and cellular stress responses. This study aimed to investigate and comparatively evaluate the protective effects of adenosine triphosphate (ATP) and taxifolin against atezolizumab-induced renal tissue injury in rats. Methods: Animals were divided into four groups: healthy (HG), atezolizumab (ATZ), ATP + atezolizumab (ATAZ), and taxifolin + atezolizumab (TXAZ). ATP (4 mg/kg, i.p.) and taxifolin (50 mg/kg, oral) were administered for six days, while atezolizumab (10 mg/kg, i.p.) was given on days 1 and 4. On day 7, renal tissues were collected for biochemical, histopathological, and double immunofluorescence analyses. Results: Atezolizumab significantly increased malondialdehyde (MDA) levels and decreased total glutathione (tGSH), superoxide dismutase (SOD), and catalase (CAT) levels, indicating enhanced oxidative stress and impaired antioxidant defense. These changes were accompanied by tubular degeneration and increased expression of apoptotic markers. Both ATP and taxifolin significantly ameliorated these alterations; however, ATP demonstrated a more pronounced protective effect. Conclusions: In conclusion, ATP and taxifolin attenuated the biochemical, histopathological, and immunofluorescence alterations associated with atezolizumab administration. ATP exhibited a more pronounced protective effect than taxifolin under the conditions of this experimental model. Nevertheless, further experimental studies are required to elucidate the mechanisms underlying these effects. Full article

(This article belongs to the Topic Oxidative Stress and Inflammation, 3rd Edition)

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27 pages, 5650 KB

Open AccessReview

Sex Differences in Mitochondrial Function: Endocrine Regulation, Immunometabolic Signaling, and Implications for Health and Disease

by Hanna Bynum and Kristin S. Edwards

Int. J. Mol. Sci. 2026, 27(11), 4966; https://doi.org/10.3390/ijms27114966 - 30 May 2026

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Abstract

Mitochondria are central regulators of cellular bioenergetics, redox balance, and signaling pathways that integrate metabolic and immune responses. Emerging evidence indicates that biological sex is an important determinant of mitochondrial function, in part through the regulatory effects of sex hormones on mitochondrial biogenesis, [...] Read more.

Mitochondria are central regulators of cellular bioenergetics, redox balance, and signaling pathways that integrate metabolic and immune responses. Emerging evidence indicates that biological sex is an important determinant of mitochondrial function, in part through the regulatory effects of sex hormones on mitochondrial biogenesis, oxidative phosphorylation, reactive oxygen species production, and quality control mechanisms. Estrogen, testosterone, and progesterone differentially modulate mitochondrial dynamics, substrate utilization, antioxidant capacity, and immune signaling, resulting in distinct mitochondrial phenotypes that may influence disease susceptibility across the lifespan. In this review, we synthesize current knowledge on the mechanistic basis of sex differences in mitochondrial function and highlight mitochondria as key mediators linking endocrine signaling to immunometabolic regulation. We discuss how mitochondrial-derived signals, including mitochondrial reactive oxygen species, mitochondrial DNA release, and cardiolipin exposure, activate inflammatory pathways such as NF-κB, cGAS–STING, and NLRP3 inflammasome signaling. These pathways may contribute to chronic inflammation, gut barrier dysfunction, and systemic metabolic disruption. We further examine the impact of major endocrine transitions, including pregnancy, the postpartum period, menopause, and androgen imbalance in conditions such as polycystic ovary syndrome, on mitochondrial function and disease risk. Particular emphasis is placed on the gastrointestinal tract as a metabolically active and mitochondria-dependent interface, where mitochondrial dysfunction may contribute to epithelial barrier disruption, microbial dysbiosis, and systemic inflammation. Finally, we discuss emerging therapeutic strategies targeting mitochondrial function, including exercise, hormone-based therapies, mitochondria-targeted antioxidants, and interventions aimed at improving mitochondrial quality control. Understanding sex-specific mitochondrial regulation may provide a framework for improved endocrine stratification, mitochondrial phenotyping, and precision medicine approaches across diverse clinical contexts. Full article

(This article belongs to the Topic Oxidative Stress and Inflammation, 3rd Edition)

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16 pages, 1102 KB

Open AccessArticle

Sustainable Valorization of Amazonian Byrsonima crassifolia (Murici): Phytochemical Profile and Antioxidant and Anti-Inflammatory Activities for Cosmetic Applications

by Julia Amanda Rodrigues Fracasso, Fernando Yutaka de Ferreira, Luísa Taynara Silvério da Costa, Maria P. M. Marques, Ana Luísa Correia Brandão, Natalia Alves Zoppe, Kássia Aiko Asano-Miyashiro, Guilherme Justiniano-Mizumoto, João Tadeu Ribeiro-Paes, Valdecir Farias Ximenes and Lucinéia dos Santos

Cosmetics 2026, 13(3), 137; https://doi.org/10.3390/cosmetics13030137 - 29 May 2026

Viewed by 448

Abstract

Considering the rich biodiversity of plant species in the Amazon region and the importance of investigating their medicinal properties as a means of valuing and preserving this biome, this study aimed to evaluate the phytochemical profile, cytotoxicity, and anti-inflammatory and antioxidant activities of [...] Read more.

Considering the rich biodiversity of plant species in the Amazon region and the importance of investigating their medicinal properties as a means of valuing and preserving this biome, this study aimed to evaluate the phytochemical profile, cytotoxicity, and anti-inflammatory and antioxidant activities of the hydroalcoholic extract of Byrsonima crassifolia leaves (HEBC). Phytochemical analysis revealed high concentrations of phenols, with emphasis on condensed tannins. In addition, the presence of catechin, a precursor of condensed tannins, was analyzed and characterized by HPLC. The cytotoxic evaluation demonstrated the absence of cytotoxicity of HEBC at concentrations of 100, 200 and 400 µg/mL at all times analyzed. Finally, HEBC exhibited strong anti-inflammatory and antioxidant activities, likely associated with the presence of catechin. Therefore, with the aim of enhancing the value of Byrsonima crassifolia and promoting its sustainable use, HEBC emerges as a promising candidate for the development of a novel phytotherapeutic agent. In future studies, HEBC is intended to be incorporated into specific formulations and subjected to further analyses to confirm its therapeutic efficacy and safety. Full article

(This article belongs to the Topic Oxidative Stress and Inflammation, 3rd Edition)

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15 pages, 1588 KB

Open AccessArticle

Combined Treatment of Nicotinamide Mononucleotide and Hyaluronic Acid Attenuates Reactive Oxygen Species and MAPK Signaling in TNF-α-Induced Human Epidermal Keratinocytes

by Yea Jung Choi, Moonseok Kang, Doeun Kim, Dong-Wook Kim, Dayeon Ham, Gabsik Yang, Sullim Lee and Ki Sung Kang

Cosmetics 2026, 13(3), 116; https://doi.org/10.3390/cosmetics13030116 - 6 May 2026

Viewed by 944

Abstract

The accumulation of oxidative damage and inflammation, induced by internal and external factors, represents a major mechanism underlying the aging of skin. Excessive reactive oxygen species (ROS) trigger mitogen-activated protein kinase (MAPK) pathways, upregulating matrix metalloproteinase (MMP) expression and facilitating extracellular matrix degradation. [...] Read more.

The accumulation of oxidative damage and inflammation, induced by internal and external factors, represents a major mechanism underlying the aging of skin. Excessive reactive oxygen species (ROS) trigger mitogen-activated protein kinase (MAPK) pathways, upregulating matrix metalloproteinase (MMP) expression and facilitating extracellular matrix degradation. Although nicotinamide mononucleotide (NMN) and hyaluronic acid (HA) possess antioxidant and dermoprotective properties, their potential combinational effects remain largely obscure. This study evaluated the impact of NMN and HA co-treatment on ROS production, MAPK signaling, MMP-1 secretion, and type I collagen secretion in TNF-α-stimulated human epidermal keratinocytes. ROS levels were assessed via DCFDA assay, while MMP-1 and COL1A1 secretion were quantified using ELISA. Additionally, the regulatory effects on ERK, JNK, and p38 phosphorylation were determined by Western blot. Synergy prediction was analyzed using the SynergyFinder platform via Highest Single Agent and Loewe models. While NMN and HA individually attenuated TNF-α-induced ROS and MMP-1 levels, co-treatment provided superior suppression and exhibited combinational interactions at specific concentrations. These findings suggest that NMN and HA combination treatment effectively modulates oxidative stress and skin-aging-related responses by regulating ROS levels and MAPK signaling pathways. Full article

(This article belongs to the Topic Oxidative Stress and Inflammation, 3rd Edition)

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27 pages, 1017 KB

Open AccessArticle

From Serum to Genome: γ-Glutamyltransferase Gene Family Variants Shape Ischemic Stroke Risk via Sex-Specific Gene–Environment Interactions

by Maria Solodilova, Elena Drozdova, Iuliia Azarova, Marina Bykanova, Olga Bushueva, Anna Puchkova, Vyacheslav Puchkov, Maxim Freidin, Mikhail Churnosov and Alexey Polonikov

Life 2026, 16(5), 721; https://doi.org/10.3390/life16050721 - 24 Apr 2026

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Abstract

Serum gamma-glutamyltransferase (GGT) is a biomarker for cardiovascular disease, but the role of its encoding gene family in ischemic stroke (IS) is unknown. This pilot study of 1288 individuals (600 cases and 688 controls) investigated GGT1, GGT5, GGT6, and GGT7 [...] Read more.

Serum gamma-glutamyltransferase (GGT) is a biomarker for cardiovascular disease, but the role of its encoding gene family in ischemic stroke (IS) is unknown. This pilot study of 1288 individuals (600 cases and 688 controls) investigated GGT1, GGT5, GGT6, and GGT7 polymorphisms using the MassARRAY-4 system. Conventional single-variant, haplotype, and diplotype analyses were complemented by Model-Based Multifactor Dimensionality Reduction (MB-MDR) with stability assessment and model prioritization. Conventional analysis identified female-specific associations for three GGT5 variants (rs8140505, rs2275984, and rs2267073; P_perm < 0.05). A common GGT5 haplotype was protective in females (P_perm = 0.02). Diplotype analysis revealed joint effects of GGT genotypes on IS risk in females (FDR < 0.05). MB-MDR uncovered complex higher-order interactions (P_perm < 0.0001): in women, 12 models represented second-order interactions between smoking and individual GGT variants. In men, 8 models centered on GGT1 rs5751909 spanning second- to fourth-order interactions with alcohol, smoking, and other GGT family members. All prioritized models passed FDR correction (q < 0.05) and achieved higher weighted composite scores. eQTL data linked these variants to regulatory networks controlling glutathione metabolism, oxidative stress, and inflammation. This study supports a novel hypothesis on the combined involvement of GGT gene family polymorphisms and pro-oxidant environmental factors in ischemic stroke predisposition, demonstrating that disease risk is shaped by sex-specific gene–environment interactions. The pronounced sexual dimorphism highlights the need for sex-specific personalized approaches: smoking cessation may be particularly impactful in women carrying GGT5 risk variants, while alcohol moderation could be prioritized in men with GGT1 risk variants. Full article

(This article belongs to the Topic Oxidative Stress and Inflammation, 3rd Edition)

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28 pages, 14728 KB

Open AccessArticle

Hepatic ACSL4 Loss Boosts Endogenous Gamma-Glutamylcysteine to Alleviate Alcoholic Liver Disease

by Ran Duan, Xin-Yi Wang, Xue Zhou, Jing-Wen Ding, Zhi-Sen Yang, Zhi-Lin Li, Yue-Yu Wang, Jia-Xin Yu and Jing-Jing Duan

Antioxidants 2026, 15(4), 438; https://doi.org/10.3390/antiox15040438 - 31 Mar 2026

Viewed by 797

Abstract

Alcoholic liver disease (ALD), secondary to chronic alcohol abuse, encompasses a spectrum of liver disorders that progress from steatosis and hepatitis to fibrosis, cirrhosis, and acute-on-chronic liver failure. It poses a considerable global health burden due to its elevated rates of associated morbidity [...] Read more.

Alcoholic liver disease (ALD), secondary to chronic alcohol abuse, encompasses a spectrum of liver disorders that progress from steatosis and hepatitis to fibrosis, cirrhosis, and acute-on-chronic liver failure. It poses a considerable global health burden due to its elevated rates of associated morbidity and mortality. The rising prevalence of ALD, coupled with the lack of approved pharmacotherapies, presents considerable unmet clinical needs. In this study, long-chain acyl-CoA synthetase 4 (ACSL4) was identified as a pathogenic driver in the context of chronic alcohol consumption. Hepatocyte Acsl4 ablation mitigated key pathological manifestations in Gao-Binge model mice, as evidenced by reduced inflammatory cell infiltration and attenuated lipid accumulation. Mechanistically, ACSL4 inhibition augmented cellular antioxidant defence through elevating gamma-glutamylcysteine (γ-GC) levels. In addition, γ-GC bound to and suppressed the expression of protein tyrosine phosphatase type IVA member 1 (PTP4A1). Both genetic silencing and pharmacological inhibition of PTP4A1 attenuated the activation of the downstream MAPK-NF-κB inflammatory cascade. Dronedarone, identified as a novel compound targeting ACSL4, demonstrated efficacy in ameliorating the progression of ALD. Overall, these findings elucidate a novel mechanism wherein ACSL4 modulates antioxidant responses via a small bioactive peptide, highlighting ACSL4 as a potential therapeutic target for ALD. Full article

(This article belongs to the Topic Oxidative Stress and Inflammation, 3rd Edition)

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18 pages, 8789 KB

Open AccessArticle

Uric Acid Induces Hepatocytes Ferroptosis Through HIF-2α/DMT1-Mediated Iron Overload

by Tao Wang, Wanbao Zheng, Meimei Guo, Jun Cao, Li Wang, Marco Sim Kah How, Youzhi Xu and Wenjie Lu

Int. J. Mol. Sci. 2026, 27(6), 2833; https://doi.org/10.3390/ijms27062833 - 20 Mar 2026

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Abstract

Hyperuricemia is associated with liver dysfunction, yet its molecular mechanisms remain unclear. This study investigated high uric acid (HUA)-induced hepatocyte injury using a hyperuricemia mouse model (HUM) and uric acid (UA)-treated L02 cells. HUM exhibited elevated aspartate aminotransferase (AST)/alanine aminotransferase (ALT) and pathological [...] Read more.

Hyperuricemia is associated with liver dysfunction, yet its molecular mechanisms remain unclear. This study investigated high uric acid (HUA)-induced hepatocyte injury using a hyperuricemia mouse model (HUM) and uric acid (UA)-treated L02 cells. HUM exhibited elevated aspartate aminotransferase (AST)/alanine aminotransferase (ALT) and pathological liver changes. Transmission electron microscopy (TEM) confirmed ferroptotic hallmarks, including mitochondrial shrinkage and increased membrane density. UA exposure upregulated NADPH oxidase 4 (NOX4), increased reactive oxygen species (ROS), and promoted lipid peroxidation (LPO), accompanied by intracellular Fe²⁺ accumulation. Mechanistically, UA increased hypoxia-inducible factor-2α (HIF-2α) expression, subsequently upregulating iron transporters divalent metal transporter 1 (DMT1) and transferrin receptor (TFRC). Deferoxamine (DFO) treatment effectively reversed Fe²⁺ overload and alleviated oxidative stress. Notably, pharmacological inhibition or genetic knockdown of HIF-2α specifically suppressed DMT1 upregulation and restored iron homeostasis, while TFRC expression remained unaffected. Blocking the HIF-2α/DMT1 axis significantly reduced LPO and mitochondrial dysfunction. These findings demonstrate that HUA induces hepatocyte ferroptosis through HIF-2α-mediated DMT1 upregulation, leading to Fe²⁺ overload and mitochondrial impairment. This study identifies the HIF-2α/DMT1 pathway as a key driver of HUA-induced liver injury and a potential therapeutic target. Full article

(This article belongs to the Topic Oxidative Stress and Inflammation, 3rd Edition)

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18 pages, 3179 KB

Open AccessArticle

Cosmetic Efficacy and Sustainability of Beer and Brewing By-Products in Skin Care: A Formulation-Driven In Vitro and In Vivo Evaluation

by Ela Hoti, Camilla Elena Di Bella, Sabina Hoti, Dolores Vargas Peregrina, Maria Giovanna Sabbieti, Dimitrios Agas, Piera Di Martino, Susi Zara and Maria Rosa Gigliobianco

Cosmetics 2026, 13(2), 63; https://doi.org/10.3390/cosmetics13020063 - 7 Mar 2026

Viewed by 2278

Abstract

The brewing process generates substantial by-products rich in potentially bioactive compounds (e.g., polyphenols and fermentation metabolites), providing a sustainable and appealing source of cosmetic ingredients. Oil-in-water (O/W) emulsions containing 20% (w/w) aqueous extracts from Bionda Triplo Malto beer, wort, [...] Read more.

The brewing process generates substantial by-products rich in potentially bioactive compounds (e.g., polyphenols and fermentation metabolites), providing a sustainable and appealing source of cosmetic ingredients. Oil-in-water (O/W) emulsions containing 20% (w/w) aqueous extracts from Bionda Triplo Malto beer, wort, and key brewing by-products (hops, yeast, and spent grain) were developed and evaluated using a combined in vitro–in vivo approach. Aqueous extracts were first screened on human immortalized dermal fibroblasts (BJ-5ta) at 0.25–1 mg/mL for cytocompatibility and antioxidant activity. Within this concentration range, no significant changes in cell viability or intracellular antioxidant capacity under UV stress were detected, suggesting cytocompatibility but limited inherent activity. When incorporated into O/W emulsions and tested at an active-equivalent concentration of 10 mg/mL, the formulations increased fibroblast metabolic activity and antioxidant response. In contrast, free extracts at 10 mg/mL showed concentration-dependent cytotoxicity for some matrices, with beer- and yeast-based emulsions demonstrating the strongest effects. The emulsions exhibited good physicochemical stability (pH ~5.7–6.2; viscosity 4750–5150 mPa·s), passed the ISO 11930:2012 challenge test, and were well tolerated in patch testing. In a double-blind, randomized split-forearm study on 50 healthy volunteers over 30 days, beer, yeast, and spent grain-based formulations improved skin parameters versus baseline. TEWL decreased (e.g., beer: 16.22 ± 5.12 to 10.77 ± 2.22 mg·m⁻²·h⁻¹; yeast: 16.29 ± 5.66 to 10.18 ± 1.08; spent grain: 14.45 ± 4.34 to 11.66 ± 2.28), hydration increased (beer: 35.15 ± 5.93 to 42.26 ± 3.78; yeast: 33.27 ± 4.87 to 42.92 ± 2.48; spent grain: 34.22 ± 5.19 to 41.16 ± 3.17, and elasticity improved for beer and yeast formulations (62.33 ± 3.27 to 70.24 ± 2.12 N/m) and yeast (61.21 ± 4.72 to 72.13 ± 5.55 N/m). Based on these findings, brewing-derived ingredients demonstrate potential as cosmetic actives, with formulation critically determining their clinical efficacy. Full article

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15 pages, 794 KB

Open AccessArticle

Lipoprotein Combine Index Is Associated with Multi-Compartment Oxidative Stress in Clinically Stable Peritoneal Dialysis Patients: A Cross-Sectional Study

by Natalia Stepanova and Lesya Korol

Biomedicines 2026, 14(2), 456; https://doi.org/10.3390/biomedicines14020456 - 18 Feb 2026

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Abstract

Background/Objectives: Background: Dyslipidaemia and oxidative stress (OS) are frequent in peritoneal dialysis (PD). The Lipoprotein Combine Index (LCI) integrates lipid parameters, but its relationship with peritoneal transport and OS is unclear. Methods: This cross-sectional study included 100 clinically stable adults on continuous [...] Read more.

Background/Objectives: Background: Dyslipidaemia and oxidative stress (OS) are frequent in peritoneal dialysis (PD). The Lipoprotein Combine Index (LCI) integrates lipid parameters, but its relationship with peritoneal transport and OS is unclear. Methods: This cross-sectional study included 100 clinically stable adults on continuous ambulatory PD with preserved ultrafiltration and adequate dialysis. LCI was calculated as (total cholesterol × triglycerides × LDL-C)/HDL-C and analyzed by tertiles. Lipid peroxidation and antioxidant markers were measured in serum, erythrocytes, urine, and spent dialysate. Multivariable regression models examined associations between LCI, peritoneal solute transport, and dialysate OS markers. Results: Higher LCI was independently associated with lower peritoneal solute transport. LCI correlated inversely with the 4 h dialysate-to-plasma creatinine ratio (ρ = −0.32, p = 0.001) and remained significant after adjustment (adjusted R² = 0.224, p < 0.001). Increasing LCI was associated with higher malondialdehyde levels in serum, urine, and dialysate (all p ≤ 0.008) and impaired antioxidant defenses, including lower total peroxidase activity in erythrocytes and dialysate (both p = 0.001), reduced serum sulfhydryl groups (p = 0.011), decreased oxidative resistance of erythrocytes, and increased peroxide-induced hemolysis (both p = 0.001). In adjusted models, logLCI was independently associated with higher dialysate malondialdehyde (p < 0.001) and lower dialysate peroxidase activity (p = 0.005). Conclusions: In clinically stable PD patients, higher lipid burden assessed by LCI is independently associated with lower peritoneal solute transport and a marked increase in systemic and local OS. Our findings suggest that dyslipidaemia may contribute to early metabolic and oxidative changes even before overt peritoneal membrane dysfunction develops. Full article

(This article belongs to the Topic Oxidative Stress and Inflammation, 3rd Edition)

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20 pages, 1982 KB

Open AccessArticle

A Novel Protective Strategy Against Metformin-Induced Renal Injury Involving Adenosine Triphosphate and Thiamine Pyrophosphate

by Huseyin Kocaturk, Fevzi Bedir, Bulent Yavuzer, Esra Tuba Sezgin, Renad Mammadov, Bahadir Suleyman, Cengiz Sarigul, Ferda Keskin Cimen, Mehmet Sefa Altay and Halis Suleyman

Int. J. Mol. Sci. 2026, 27(4), 1825; https://doi.org/10.3390/ijms27041825 - 14 Feb 2026

Viewed by 721

Abstract

Metformin is widely used in type 2 diabetes, but its effects on oxidative and inflammatory pathways remain controversial. Beyond glycemic control, it may promote lactic acidosis by impairing mitochondrial metabolism and pyruvate flux. The potential renoprotective roles of adenosine triphosphate (ATP) and thiamine [...] Read more.

Metformin is widely used in type 2 diabetes, but its effects on oxidative and inflammatory pathways remain controversial. Beyond glycemic control, it may promote lactic acidosis by impairing mitochondrial metabolism and pyruvate flux. The potential renoprotective roles of adenosine triphosphate (ATP) and thiamine pyrophosphate (TPP) remain poorly defined. This study aimed to evaluate whether ATP and TPP mitigate metformin-induced renal injury through biochemical and histopathological assessments. Wistar rats were randomly divided into six groups: control, ATP, TPP, metformin, ATP + metformin, and TPP + metformin. Metformin (50 mg/kg, oral), ATP (4 mg/kg, intraperitoneal), or TPP (20 mg/kg, intraperitoneal) was administered daily for 10 days. Oxidative stress markers, inflammatory cytokines, renal histopathology, and serum creatinine, BUN, lactate, and LDH levels were evaluated. Metformin induced significant oxidative stress, inflammation, metabolic disturbance, and renal injury. ATP provided partial protection, whereas TPP markedly restored redox balance, reduced inflammation, and preserved renal histology. TPP confers superior protection against metformin-induced renal injury compared with ATP by modulating oxidative, inflammatory, and metabolic pathways, highlighting its therapeutic potential in preventing metformin-related nephrotoxicity. Full article

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21 pages, 7325 KB

Open AccessArticle

Choline Deficiency Drives the Inflammation–Fibrosis Cascade: A Spatiotemporal Atlas of Hepatic Injury from Weeks 6 to 10

by Shang Li, Guoqiang Zhang, Xiaohong Li, Xu Zhao, Axi Shi, Qingmin Dong, Changpeng Chai, Xiaojing Song, Yuhui Wei and Xun Li

Antioxidants 2026, 15(1), 110; https://doi.org/10.3390/antiox15010110 - 15 Jan 2026

Cited by 2 | Viewed by 1292

Abstract

Metabolic dysfunction-associated steatotic liver disease (MASLD) is strongly linked to systemic metabolic disturbances and features a lipid-driven cascade that promotes hepatic inflammation and fibrosis. Choline insufficiency contributes to disease advancement by altering phospholipid turnover and redox homeostasis; however, its spatial and temporal regulatory [...] Read more.

Metabolic dysfunction-associated steatotic liver disease (MASLD) is strongly linked to systemic metabolic disturbances and features a lipid-driven cascade that promotes hepatic inflammation and fibrosis. Choline insufficiency contributes to disease advancement by altering phospholipid turnover and redox homeostasis; however, its spatial and temporal regulatory roles throughout MASLD progression remain insufficiently defined. A 10-week high-fat, choline-deficient (HFCD) mouse model was established, and liver pathology was evaluated at weeks 6, 8, and 10. Time-resolved assessments combined untargeted metabolomics, magnetic resonance imaging–proton density fat fraction (MRI-PDFF), serum biochemistry, histological staining, immunofluorescence, and transmission electron microscopy to characterize dynamic alterations in lipid metabolism, redox status, inflammation, and fibrogenesis. The HFCD diet produced a clear temporal sequence of liver injury. Steatosis, phosphatidylcholine depletion, and early antioxidant loss appeared by week 6. By week 8, mitochondrial structural damage and pronounced cytokine elevation were evident. At week 10, collagen deposition and α-SMA activation signaled fibrotic progression. Metabolomics indicated significant disruptions in pathways related to ATP-binding cassette (ABC) transporters, one-carbon metabolism, and the tricarboxylic acid (TCA) cycle. Using integrated analytical strategies, this study suggests that choline deficiency may be associated with a time-dependent pathological cascade in MASLD, beginning with phospholipid destabilization and extending to altered mitochondria–endoplasmic reticulum crosstalk at mitochondria-associated membranes, alongside amplified oxidative–inflammatory responses, which collectively may contribute to progressive fibrogenesis as the disease advances. Full article

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14 pages, 1469 KB

Open AccessArticle

Mitigating Hydroxychloroquine-Induced Oxidative Liver Damage: The Roles of Adenosine Triphosphate, Liv-52, and Their Combination in Rats

by Meryem Yalvac Kandefer, Esra Tuba Sezgin, Bahadir Suleyman, Ferda Keskin Cimen, Fulya Memiş, Mine Gulaboglu and Halis Suleyman

Int. J. Mol. Sci. 2026, 27(1), 421; https://doi.org/10.3390/ijms27010421 - 31 Dec 2025

Cited by 2 | Viewed by 1261

Abstract

Hydroxychloroquine (HCQ), originally developed as an antimalarial agent, has been associated with hepatotoxic effects in experimental and clinical settings. Our study was designed to evaluate the effects of this agent on liver toxicity and to understand the protective roles of adenosine triphosphate (ATP), [...] Read more.

Hydroxychloroquine (HCQ), originally developed as an antimalarial agent, has been associated with hepatotoxic effects in experimental and clinical settings. Our study was designed to evaluate the effects of this agent on liver toxicity and to understand the protective roles of adenosine triphosphate (ATP), Liver-52 (Liv-52), and their combination. Male Wistar rats (250–280 g) were randomly assigned to five groups (n = 6): healthy control (C), HCQ only (H), ATP plus HCQ (AH), Liv-52 plus HCQ (LH), and ATP–Liv-52 plus HCQ (ALH). ATP (4 mg/kg) was administered intraperitoneally once daily, whereas Liv-52 (20 mg/kg) was administered orally via gavage. One hour later, all groups except C received HCQ (120 mg/kg, orally, twice daily). All treatments were continued for seven consecutive days. At the end of the experiment, serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels were measured, and liver tissues were analyzed for malondialdehyde (MDA), total glutathione (GSH), superoxide dismutase (SOD), and catalase (CAT) activities, along with histopathological evaluation. HCQ administration significantly increased oxidative stress, as evidenced by elevated MDA levels (p < 0.01) and reduced antioxidant parameters, including GSH, SOD, and CAT (p < 0.05), accompanied by prominent histopathological damage. Treatment with ATP or Liv-52 markedly ameliorated these alterations by decreasing MDA and restoring antioxidant markers. The combination treatment was observed to exhibit the most pronounced protective effect; it significantly reduced MDA levels, improved GSH, SOD, and CAT levels more effectively, and produced significant decreases in AST and ALT values (p < 0.05). Full article

(This article belongs to the Topic Oxidative Stress and Inflammation, 3rd Edition)

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48 pages, 2461 KB

Open AccessReview

Role of Matricellular Proteins in Endothelial Cell Inflammation and Atherosclerosis

by Ravi Varma Aithabathula, Santosh Kumar and Bhupesh Singla

Antioxidants 2025, 14(11), 1338; https://doi.org/10.3390/antiox14111338 - 6 Nov 2025

Cited by 3 | Viewed by 2572

Abstract

The vascular endothelium serves as a critical barrier preventing the transmigration of monocytes, circulating lipoproteins, and other molecules into the subendothelial space, and plays a vital role in regulating vascular tone. A dysfunctional and inflamed endothelial layer in response to disturbed blood flow [...] Read more.

The vascular endothelium serves as a critical barrier preventing the transmigration of monocytes, circulating lipoproteins, and other molecules into the subendothelial space, and plays a vital role in regulating vascular tone. A dysfunctional and inflamed endothelial layer in response to disturbed blood flow or other proatherogenic risk factors is the initiating event in the pathogenesis of atherosclerosis, suggesting the importance of an intact and properly functioning endothelium in preventing the onset and progression of this disease. Accumulated evidence demonstrates the significant role of matricellular proteins, which are non-structural and secretory extracellular matrix (ECM) proteins, in the development of atherosclerosis. These proteins exert multifaceted effects on endothelial cells (ECs) ranging from reactive oxygen species (ROS) production, endoplasmic reticulum stress, and expression of adhesion molecules to autophagy and compromised barrier function via stimulating various molecular mechanisms. Given the critical roles of these processes in EC function and atherosclerosis, a better understanding of signaling pathways governed by matricellular proteins in ECs is required to develop therapeutic strategies for suppressing or preventing atherosclerosis and related cardiovascular diseases (CVDs). This review comprehensively summarizes the existing literature on the diverse roles of matricellular proteins in regulating EC inflammation and function, and highlights their potential as viable therapeutic targets for maintaining vascular health and inhibiting the progression of atherosclerosis. Full article

(This article belongs to the Topic Oxidative Stress and Inflammation, 3rd Edition)

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17 pages, 1319 KB

Open AccessArticle

Oxidative Stress Score as an Indicator of Pathophysiological Mechanisms Underlying Cardiovascular Disease in Kidney Transplant Recipients

by Valera-Arévalo Gemma, Paula Jara Caro, María del Mar Rodríguez-San Pedro, Claudia Yuste, María Gabriela Ortiz-Diaz, Rafael Ramírez, Matilde Alique, Natalia Guerra-Pérez, Julia Carracedo and Enrique Morales

Oxygen 2025, 5(4), 20; https://doi.org/10.3390/oxygen5040020 - 16 Oct 2025

Cited by 2 | Viewed by 1892

Abstract

Chronic kidney disease is closely associated with an increased risk of cardiovascular disease. Although kidney transplantation represents the treatment of choice for patients with end-stage chronic kidney disease, it is also linked to significant cardiovascular risk. This study aimed to evaluate the relationship [...] Read more.

Chronic kidney disease is closely associated with an increased risk of cardiovascular disease. Although kidney transplantation represents the treatment of choice for patients with end-stage chronic kidney disease, it is also linked to significant cardiovascular risk. This study aimed to evaluate the relationship between cardiovascular pathology and oxidative status in kidney transplant recipients, while also assessing the influence of disease etiology and humoral immune response on oxidative imbalance. A cross-sectional analysis was conducted in individuals with advanced chronic kidney disease (n = 36) and kidney transplant recipients (n = 40). A total of 18 healthy subjects were included. The enzymatic activities of xanthine oxidase, superoxide dismutase, and glutathione peroxidase, and levels of lipid peroxidation products, oxidized glutathione, and reduced glutathione were measured using spectrophotometry in plasma and mononuclear and polymorphonuclear leukocytes isolated using Ficoll density gradients. Individual oxidative status was evaluated using OXYSCORE. Kidney transplantation was associated with a higher incidence of cardiovascular disease (p < 0.01) and increased levels of both prooxidant (p < 0.01) and antioxidant parameters (p < 0.01). Elevated OXYSCORE values were observed particularly in patients with nephroangiosclerosis, diabetic kidney disease, polycystic kidney disease (p < 0.05), and cardiovascular comorbidities (p < 0.001). Additionally, the presence of anti-graft antibodies correlated with higher oxidative scores. These findings suggest that OXYSCORE may serve as a potential indicator of cardiovascular damage in kidney transplant recipients. Full article

(This article belongs to the Topic Oxidative Stress and Inflammation, 3rd Edition)

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11 pages, 3848 KB

Open AccessArticle

Preventive and Therapeutic Effects of Hydrogen-Generating Si-Based Agent on Pressure Ulcers in Mice

by Naoya Otani, Takaki Oue, Yuki Kobayashi, Hikaru Kobayashi, Koichi Tomita and Tateki Kubo

Biomedicines 2025, 13(10), 2475; https://doi.org/10.3390/biomedicines13102475 - 11 Oct 2025

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Abstract

Objectives: As a known antioxidant, hydrogen has been useful for treating pressure ulcers. However, conventional methods of hydrogen administration have limitations with regard to dosage and continuity of hydrogen intake. This study evaluated the efficacy of a novel Si-containing agent that can [...] Read more.

Objectives: As a known antioxidant, hydrogen has been useful for treating pressure ulcers. However, conventional methods of hydrogen administration have limitations with regard to dosage and continuity of hydrogen intake. This study evaluated the efficacy of a novel Si-containing agent that can generate substantial quantities of hydrogen to treat pressure ulcers in an in vivo mouse model. Methods: The back skin and subcutaneous tissue of mice were compressed with magnets for 12 h. Changes in the ulcer area after release of compression, histological findings, degree of apoptosis, and expression levels for oxidative stress markers and inflammation-related cytokines were compared between mice fed a normal diet (control group) and those fed a 2.5 wt% Si-based diet (Si group). Results: The Si group had a significantly smaller ulcer area and shorter healing period than the control group. Moreover, inflammatory responses, apoptotic activity, and oxidative stress within the ulcer tissue were suppressed significantly in the Si group. Conclusions: Oral intake of the Si-based agent can potentially treat and prevent pressure ulcers by regulating apoptosis, oxidative stress, and inflammatory responses. Full article

(This article belongs to the Topic Oxidative Stress and Inflammation, 3rd Edition)

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16 pages, 4051 KB

Open AccessArticle

Protective Effect of Exogenous Adenosine Triphosphate Against Ocular Toxicity of Linezolid in Rats

by Cenap Mahmut Esenulku, Ibrahim Cicek, Ahmet Mehmet Somuncu, Bulent Yavuzer, Esra Tuba Sezgin, Tugba Bal Tastan, Nurinisa Yücel, Ezgi Karatas and Halis Suleyman

Life 2025, 15(10), 1587; https://doi.org/10.3390/life15101587 - 11 Oct 2025

Cited by 2 | Viewed by 993

Abstract

Linezolid, a synthetic antimicrobial agent, may induce oxidative damage in ocular tissues, particularly in the optic nerve. Adenosine triphosphate (ATP) is involved in the production of antioxidants that scavenge and neutralize reactive oxygen species. This study aims to evaluate the potential protective effect [...] Read more.

Linezolid, a synthetic antimicrobial agent, may induce oxidative damage in ocular tissues, particularly in the optic nerve. Adenosine triphosphate (ATP) is involved in the production of antioxidants that scavenge and neutralize reactive oxygen species. This study aims to evaluate the potential protective effect of exogenous ATP against linezolid-induced ocular damage in rats, in comparison with methylprednisolone. Wistar-type rats were divided into five groups as follows: healthy (HG), ATP-only (ATPG), linezolid-only (LZDG), ATP + linezolid (ATLDG), and methylprednisolone + linezolid groups (MPLDG). Oxidative stress markers, antioxidant biomarkers, and proinflammatory cytokines were analyzed in isolated ocular tissues. Optic nerve tissue was also evaluated histopathologically. Linezolid administration increased the oxidative stress marker MDA and the proinflammatory cytokine TNF-α, while decreasing antioxidant parameters such as tGSH, SOD and CAT in rat ocular tissues, compared to the healthy group. However, it did not significantly alter serum troponin I levels. Histopathological analysis revealed that linezolid induced oxidative damage and inflammation in optic nerve tissue, with marked glial alterations. ATP administration reduced linezolid-induced oxidative stress in ocular tissue, as indicated by decreased MDA levels. It also enhanced antioxidant defenses by increasing tGSH, SOD, and CAT levels. In addition, ATP lowered proinflammatory cytokine levels, thereby alleviating inflammation. These effects collectively contributed to the restoration of biochemical parameters toward normal levels. In addition, ATP mitigated linezolid-induced optic nerve damage and glial alterations. The critical role of ATP in reducing oxidative stress, restoring antioxidant balance, and suppressing inflammation may represent a promising therapeutic approach for linezolid-induced ocular toxicity. Full article

(This article belongs to the Topic Oxidative Stress and Inflammation, 3rd Edition)

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18 pages, 3287 KB

Open AccessArticle

In Silico and In Vitro Studies of Anti-Inflammatory, Anti-Oxidative Stress, and Anti-Apoptosis Effect of 7-Octenoic Acid Derived from Moringa oleifera Lam., on LPS-Induced Monocyte-Derived Macrophages (MDM)

by Kittipong Srimuang, Watunyoo Buakaew, Yordhathai Thongsri, Krai Daowtak, Pachuen Potup, Antonio Ferrante and Kanchana Usuwanthim

Int. J. Mol. Sci. 2025, 26(18), 8911; https://doi.org/10.3390/ijms26188911 - 12 Sep 2025

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Abstract

While Moringa oleifera Lam. (MO) extracts are known to have various bioactive properties, including anti-inflammatory properties, the components responsible still remain to be identified. This study explores the protective effects of the MO component, 7-octenoic acid (7OCT) in LPS-stimulated THP-1 macrophage inflammatory responses. [...] Read more.

While Moringa oleifera Lam. (MO) extracts are known to have various bioactive properties, including anti-inflammatory properties, the components responsible still remain to be identified. This study explores the protective effects of the MO component, 7-octenoic acid (7OCT) in LPS-stimulated THP-1 macrophage inflammatory responses. The compound significantly downregulated the production of the pro-inflammatory cytokines TNF-α, IL-1β, and IL-6, as well as the expression of inflammation-related genes NFKB1, PTGS2, and NOS2. Additionally, it inhibited the nuclear translocation of NF-κB p65, a key transcription factor of inflammatory signaling cascade. Effects on oxidative stress showed that 7OCT inhibited LPS-induced NADPH oxidase 2 (NOX2) component genes including CYBB, CYBA, NCF1, NCF2, and NFE2L2, along with phosphorylated NOX2 and p47^phox proteins. The compound reduced the expression of TP53, BAX, CASP3, and CASP7, while enhancing BCL2 expression and Bcl-2 protein levels, suggesting an effect on apoptosis. Decreased levels of BAX, caspase-3, and cleaved caspase-3 proteins further confirmed its anti-apoptotic effect. Our findings suggest that 7OCT exhibits strong anti-inflammatory, antioxidant, and anti-apoptotic properties. Full article

(This article belongs to the Topic Oxidative Stress and Inflammation, 3rd Edition)

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