Search Results (1,785)

Aflatoxin B₁ (AFB₁) is a major mycotoxin in poultry feeds that can impair growth and damage multiple organs. This study evaluated whether dietary rosemary (Rosmarinus officinalis L.) could mitigate AFB₁-induced alterations in broiler chickens. Forty-five one-day-old male Ross 308 broilers were assigned for 21 days to a control diet, a diet containing 250 µg/kg AFB₁, or the AFB₁-contaminated diet supplemented with 0.5% rosemary. Growth performance, relative organ weights, hematologic and serum biochemical profiles, hepatic and renal histopathology, and intestinal and glomerular morphometry were evaluated. AFB₁ significantly reduced body weight on day 14 (p = 0.028), worsened feed conversion ratio on days 7 and 14 (p = 0.001 and p = 0.011, respectively), decreased feed intake on day 21 (p = 0.004), and reduced relative bursal weight (p = 0.036). Rosemary supplementation significantly improved feed conversion during the first two weeks and restored feed intake on day 21 to values comparable with the Control group. Although body weight in the AF+PHY group was 22.3% higher than in the AF group on day 14, this pairwise difference was not statistically significant; nevertheless, the magnitude of this numerical response may be practically relevant by reducing early AFB₁-associated performance losses. AFB₁ also increased hepatic and glomerular lesion severity and reduced duodenal villus height (p = 0.012) and villus-plus-crypt length (p = 0.006). Rosemary significantly reduced bile duct epithelial degeneration (p < 0.001), overall hepatic lesion severity, and glomerular obliteration (p < 0.001), reducing the mean glomerular obliteration score by 41.3% relative to the AF group (1.55 vs. 2.64), while preserving duodenal villus-plus-crypt length at values not significantly different from the Control group. These findings indicate that 0.5% dietary rosemary partially mitigates AFB₁ toxicity, with statistically supported improvements in feed efficiency and attenuation of selected hepatic, renal, and intestinal structural alterations. Full article

In broiler farming, high-fat (HF) diets are frequently incorporated, often leading to hepatic steatosis, oxidative stress, and gut damage. 1-Deoxynojirimycin (DNJ) has emerged as a promising feed additive in animal husbandry due to its significant role in enhancing animal health. This study assessed the protective effects of DNJ-enriched mulberry extract (DNJ) on liver and gut health in broilers subjected to an HF diet, with particular emphasis on the liver-gut interaction. A total of 360 one-day-old Arbor Acres broilers were initially raised on a basal diet for 20 days, after which they were assigned to one of three dietary treatments from days 21 to 42: a control diet (CON), an HF diet, and an HF diet supplemented with 80 mg/kg DNJ (HF + DNJ). By day 42, broilers on the HF diet exhibited increased body weight, feed intake, and body weight gain, alongside reduced feed conversion efficiency. In contrast, DNJ supplementation reduced body weight without affecting feed intake in the HF diet group. It lowered liver T-CHO and LDL-C levels, increased SOD and CAT activities, and decreased MDA. Histological analyses showed that DNJ preserved intestinal mucosal structure and epithelial tight junctions. DNJ supplementation enriched microbes like Actinobacteriota and Baceroidota and reversed the HF-induced Firmicutes-to-Bacteroidota ratio. Furthermore, Bifidobacterium pullorum and Bacteroidota were positively correlated with antioxidant markers. In conclusion, dietary DNJ-enriched mulberry extract serves as an effective functional feed substance that mitigates HF-induced metabolic syndromes in broilers by balancing lipid metabolism, enhancing antioxidant defenses, safeguarding intestinal barrier integrity, and restoring healthy microbial community structures along the liver-gut axis. Full article

Background/Objectives: Polydeoxyribonucleotide (PDRN) has anti-inflammatory and tissue-protective properties associated with activation of the adenosine A_2A receptor (A_2AR). Although hepatoprotective actions of PDRN have previously been described, its potential association with high-mobility group box 1 (HMGB1)-related inflammatory responses and hepatic macrophage accumulation during acute liver injury (ALI) is not fully understood. This study examined whether PDRN affects HMGB1- and monocyte chemoattractant protein-1 (MCP-1)-associated responses together with hepatic macrophage accumulation in ALI. Methods: ALI was induced in ICR mice by carbon tetrachloride (CCl₄) administration. PDRN was administered either alone or together with the selective A_2AR antagonist 3,7-dimethyl-1-propargylxanthine (DMPX). Serum levels of aspartate aminotransferase, alanine aminotransferase, and lactate dehydrogenase were quantified. Histological alterations were evaluated using hematoxylin and eosin staining. Hepatic macrophage accumulation was assessed by F4/80 immunofluorescence staining. Enzyme-linked immunosorbent assays were used to quantify HMGB1, MCP-1, interleukin-10 (IL-10), cyclic adenosine monophosphate (cAMP), and A_2AR. Results: PDRN significantly reduced serum markers of liver injury and attenuated histopathological damage following CCl₄ administration. PDRN treatment also decreased F4/80-positive macrophage accumulation in the hepatic tissue. In addition, PDRN reduced HMGB1 and MCP-1 levels in both the serum and liver tissues while significantly increasing IL-10, cAMP, and A_2AR levels. Conclusions: PDRN attenuated CCl₄-induced ALI and was associated with reduced HMGB1 and MCP-1 levels, decreased hepatic macrophage accumulation, and increased A_2AR/cAMP signaling. These findings suggest that modulation of macrophage-associated inflammatory responses may contribute to the hepatoprotective effects of PDRN. Full article

Policosanol (sugarcane wax alcohol), phosphatidylserine, and Ginkgo biloba leaf extract are Ministry of Food and Drug Safety (MFDS), Republic of Korea-listed functional foods for health-promoting effects. Herein, a combination of policosanol, phosphatidylserine, and G. biloba leaf extract (hereafter PPG) was investigated against metabolic stress induced by a high-cholesterol, high-galactose (HCHG) diet in hyperlipidemic and hyperglycemic zebrafish. After 9 weeks of feeding, the zebrafish following the HCHG diet co-supplemented with PPG exhibited a significant 14.1% (p < 0.02) reduction in body weight and higher zebrafish survivability compared to the HCHG-supplemented group. Significantly reduced total cholesterol (TC, 1.2-fold), triglycerides (TG, 1.4-fold), low-density lipoprotein cholesterol (LDL-C, 1.3-fold), and glucose levels (1.2-fold), along with a 1.5-fold (p = 0.003) elevated high-density lipoprotein cholesterol (HDL-C), were observed in the PPG co-supplemented group relative to the HCHG group. In addition, the HCHG-elevated plasma malondialdehyde (MDA), diminished ferric ion reduction activity (FRA), and paraoxonase (PON)-like activity significantly (p < 0.001) reverted by 1.6-fold, 1.4-fold, and 1.6-fold, respectively, by co-supplementation with PPG. Consistently, the plasma from the PPG-supplemented group showed greater ability to prevent carboxymethyllysine (CML)-induced apoptotic death, altered heart rate, and developmental deformities in zebrafish embryos. Moreover, PPG exerted significant protective effects against HCHG-induced hepatomegaly and fatty liver, accompanied by marked inhibition of hepatic interleukin (IL)-6 and reactive oxygen species (ROS) generation. Consistently, PPG supplementation inhibits ROS generation and senescence in the liver, intestine, brain, kidney, testis and ovary and protects the organ damage caused by exposure to HCHG. Similarly, in intestinal tissue, HCHG-induced fibrosis and oxidative stress were mitigated by the co-supplementation of PPG. The findings indicate that PPG is an effective combination for preventing dyslipidemia, oxidative stress, inflammation, and multi-organ damage associated with HCHG-mediated metabolic stress in zebrafish. Full article

Background: Disrupted bile acid homeostasis drives alcoholic steatohepatitis (ASH) progression, which has become a new therapeutic target for ASH. This study examined the impact and underlying mechanisms of polysaccharides from Balanophora harlandii Hook. (BHP) on bile acid synthesis and liver damage in ASH. Methods: A Binge-on-Chronic alcohol exposure model was established to assess the impact of BHP on alcohol-induced liver damage and bile acid (BA) metabolism. Fexaramine and glycine-β-MCA (Gly-MCA) were also utilized to explore a crucial role of intestinal FXR signaling activity in ASH mice. In vitro, intestinal epithelial cells were stimulated with alcohol to impair FXR activity. Results: BHP treatment mitigated weight loss, reduced hepatic lipid accumulation and inflammation in chronic alcohol-fed mice, demonstrating a significant hepatoprotective effect against ASH. Mechanistically, BHP treatment reduced intestinal conjugated BA levels and activated FXR-FGF15 signaling, which inhibited hepatic BA synthesis and mitigated the toxic effects of hepatic BA accumulation in ASH. However, the suppression of intestinal FXR activation notably diminished the ability of BHP to regulate BA synthesis and prevent liver damage in ASH mice. In vitro, BHP treatment also activated FXR signaling in intestinal epithelial cells, counteracting alcohol-induced FXR activity damage. Conclusions: BHP treatment effectively alleviated liver damage in mice with chronic alcohol exposure through reducing hepatic BA synthesis. The mechanisms behind the hepatoprotective effects of BHP suggested that correcting the shift in the intestinal BA profile and/or the intestinal FXR-FGF15 signaling are the potential therapies against alcoholic liver injury. Full article

Fatty liver hemorrhagic syndrome (FLHS) is a prevalent metabolic disease in laying hens, causing severe economic losses. A previous study showed that conjugated linoleic acids (CLA) alleviated estrogen-induced FLHS in chickens, but the mechanism remains unclear. In the present study, we found that CLA improved serum lipid homeostasis, reduced hepatic lipid accumulation, and enhanced antioxidant activity in FLHS chickens. Transcriptome analysis identified differentially expressed genes enriched in inflammatory response, lipid homeostasis, carbohydrate metabolism, and mitogen-activated protein kinase (MAPK)/peroxisome proliferator-activated receptor (PPAR)/insulin signaling pathways. Metabolome analysis detected differentially abundant metabolites enriched in bile secretion, thyroid hormone synthesis, the insulin signaling pathway, and glycerophospholipid metabolism. Integrated analyses revealed that CLA reshaped the hepatic metabolic profile by upregulating protective metabolites (such as ubiquinol) and downregulating pro-inflammatory/lipogenic metabolites (such as 15-hydroperoxyeicosa-8Z,11Z,13E-trienoate), which synergized with key gene regulation (fatty acid synthase, jun proto-oncogene, and fatty acid desaturase 2) and core pathway activity (MAPK/nuclear factor kappa-B inhibition, PPARα activation). The multi-omics study using an estradiol-induced rooster FLHS model elucidated the molecular regulatory network of CLA against hepatic steatosis and liver injury, and provided preliminary mechanistic clues for developing CLA functional additives to prevent and treat FLHS in commercial laying hens. Full article

Microplastics (MPs) are emerging pollutants widespread in aquatic environments; however, their effects across the different life stages of aquatic organisms remain poorly understood. This systematic review integrates recent experimental results on the developmental, physiological, and neurobehavioral effects of MP exposure on zebrafish (Danio rerio), a popular model organism for ecotoxicology research. A PRISMA-guided search using Web of Science (WoS) and Scopus as databases generated 581 articles, which were screened to 60 eligible articles. The collated results showed that MP toxicity at various life stages of zebrafish was strongly related to the physicochemical properties of MPs and exposure conditions. In terms of developmental toxicity, peer-reviewed publications assessing specific MP physicochemical properties—polymer type, size, concentration, shape, and degree of aging—reported concentration-dependent effects, with increasing MP concentrations generally associated with growth inhibition, cardiac dysfunction, increased malformations, and lower hatching rate, particularly at ≥10 mg/L to ≥100 mg/L. However, several studies noted that under particle-based exposure scenarios, MP toxicity exhibited threshold-like or non-monotonic responses, attributed to aggregation, bioavailability, and uptake dynamics. Weathered and artificially aged MPs exhibited higher embryotoxicity and neurodevelopmental toxicity, including changes in gene expression of neurons, decreased integrity of motor neurons, and impaired retinal development, compared with “virgin” MPs. In terms of physiological endpoints, oxidative imbalance like changes in the activity of antioxidant enzymes (superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx)), lipid peroxidation, inflammation, and disruption of tight junctions have been reported as key toxicity pathways. Chronic MP exposure in zebrafish also caused changes in the gut microbiota, hepatic metabolism, endocrine disruption, reproductive damage, thyroid function disruption, and genotoxicity in zebrafish. In terms of neurobehavioral effects, changes in locomotor activity, anxiety response, neurotransmitter homeostasis, and acetylcholinesterase function, have been observed, in both larvae and adults, with a potentiation effect in aged MP exposure. Finally, this systematic review found major limitations for inter-study comparisons because of inconsistencies and differences in methodology applied related to MP concentration, simulation of natural MP aging, and MP dose measurements. Full article

This study investigated the combined administration of raffinose (RAF) and isoflavones (ISO) to enhance ISO bioavailability and alleviate high-fructose (HF)-induced liver damage. Mice were administered 20% HF water with RAF, ISO, or their combination (RAF + ISO) for 10 weeks. UPLC-qTOP/MS analysis showed that RAF + ISO significantly increased total ISO levels in serum, urine, and feces by 18.5%, 37.4%, and 13.6%, respectively, compared to ISO alone (p < 0.05). The combined treatment more effectively reduced HF-induced weight gain, visceral fat accumulation, and dyslipidemia, partly through suppression of FAS and ACC gene expression (p < 0.05). Furthermore, RAF + ISO more efficiently attenuated hepatic oxidative stress, inflammation, and insulin resistance than either agent alone. Liver enzyme activities (AST, ALT, ALP) were significantly reduced by RAF + ISO treatment, consistent with histopathological improvements in liver tissue. These findings demonstrate that RAF enhances the systemic availability of ISO and potentiates its protective effects against HF-induced metabolic and hepatic alterations. Full article

Acetaminophen (APAP) represents a major cause of drug-induced liver injury (DILI), and effective pharmacological interventions remain limited. Annexin A5 (AnxA5), a Ca²⁺-dependent phospholipid-binding protein, participates in diverse biological processes related to tissue repair. In this study, we evaluated AnxA5 expression in APAP-challenged mouse livers and clinical samples from patients with liver injury. Using hepatic cell lines AML12 and HepG2, we performed overexpression-based functional assays to assess the cytoprotective effects of AnxA5 against APAP toxicity. Co-immunoprecipitation assays were applied to characterize protein interactions, and mitochondrial functional parameters were measured to dissect the underlying molecular mechanism. We found that AnxA5 was significantly upregulated in both APAP exposed mice and APAP DILI patients. Cellular functional assays showed that AnxA5 overexpression mitigated APAP triggered cytotoxicity in AML12 and HepG2 cells. Mechanistically, AnxA5 bound to voltage dependent anion channel 1 (VDAC1), restrained VDAC1 mediated mitochondrial Ca²⁺ influx, and suppressed VDAC1 oligomerization, which further inhibited mitochondrial permeability transition pore (mPTP) opening. In an APAP-induced liver injury mouse model, exogenous recombinant AnxA5 treatment maintained mitochondrial integrity and ameliorated hepatic inflammation and liver damage. Collectively, our data reveal AnxA5 as an endogenous mitochondrial protective factor and support its therapeutic potential against APAP-induced liver injury. Full article

Mitochondria and peroxisomes are critical for hepatic energy metabolism, lipid homeostasis, and reactive oxygen species (ROS) detoxification. In chronic hepatitis C virus (HCV) infection, continuous injury leads to cirrhosis; however, the spatial arrangement and reversibility of organelle dysfunction remain poorly understood. This study aimed to examine the zonal distribution of mitochondrial and peroxisomal injury in liver biopsies and elucidate the role of circulating cell-free mitochondrial DNA (ccfDNA) in patients with chronic HCV and cirrhosis following antiviral therapy. We employed advanced microscopy imaging and transcriptomic analysis of liver biopsies and quantified ccf-mtDNA as a noninvasive marker of mitochondrial injury in the peripheral blood of these patients. Transcriptomic data revealed alterations in mitochondrial and peroxisomal pathway alterations in HCV-infected patients. The imaging data displayed distinct zone-specific patterns of organelle damage. Following viral removal, significant improvement in mitochondrial and peroxisomal protein expression were noted, indicating partial recovery of organelle integrity following viral clearance; whether this reflects true subcellular regeneration or an early stage of a longer recovery process remains to be determined. Additionally, we showed that ccf-mtDNA quantitatively reflects intrahepatic mitochondrial dysfunction, indicating its potential as a diagnostic biomarker in therapeutic approaches. These findings indicate that organelle injury in chronic HCV is spatially patterned, disease severity-dependent, and partially reversible following antiviral therapy. Full article

Metabolic dysfunction-associated steatotic liver disease (MASLD) and heart failure (HF) frequently coexist within a shared cardiometabolic environment, yet their mitochondrial abnormalities are stage- and phenotype-dependent rather than uniform. In MASLD, mitochondrial adaptation evolves from increased oxidative metabolism in early steatosis toward impaired respiratory flexibility, oxidative stress, and defective quality control with disease progression, whereas the failing myocardium develops reduced energetic reserve and altered substrate utilization. These organ-specific disturbances can modify mitochondria-linked metabolites, mitochondrial damage-associated molecular patterns, stress-responsive endocrine mediators, and extracellular vesicle-associated mitochondrial cargo. However, similar mitochondrial abnormalities or circulating signals in the liver and heart do not by themselves establish direct inter-organ communication. This review distinguishes shared systemic drivers and organ-intrinsic mitochondrial stress from source-resolved cardio-hepatic signaling, highlighting hepatic ketogenesis, fibroblast growth factor 21 (FGF21), mitochondrial DNA (mtDNA)-dependent inflammatory pathways, and extracellular vesicle-mediated cargo transfer as mechanistically distinct examples with different levels of evidence. We further discuss biomarker limitations, HF-related hemodynamic liver injury, and therapeutic strategies ranging from established cardiometabolic unloading to emerging mitochondria-centered interventions. A stage-, phenotype-, and source-resolved framework may improve interpretation of mitochondrial signals and guide future mechanistic and translational studies in the MASLD–HF overlap. Full article

Fusarium mycotoxins are major contaminants of human and animal feed and pose significant risks to health. A recent recommendation from the European Commission drastically decreased the maximum tolerated concentrations of fumonisins (FBs) and deoxynivalenol (DON) in poultry feed. The objectives of this study were to characterize the effects of a 14-day exposure to a diet containing 7.5 mg FB1 + FB2/kg, 2.5 mg DON/kg and 0.6 mg zearalenone (FDZ diet) in turkeys and chickens, and to assess the persistence of these effects following withdrawal of the contaminated diet. No clinical signs of toxicity were observed in either species, and markers of hepatic oxidative damage remained unchanged. In contrast, sphingolipidome alterations were detected, being more pronounced in turkeys than chickens and more persistent in the liver than in plasma. The C22–C24:C16 ratios measured across several sphingolipid (SL) classes emerged as sensitive biomarkers of FB exposure, whereas the sphinganine:sphingosine ratio (Sa:So) remained unchanged. Determination of the 90th percentile (P90) thresholds for SL ratios in unexposed animals provided good-to-excellent discrimination between exposed and unexposed animals. Notably, this conservative percentile-based approach detected FB exposure using the Sa:So ratio despite the absence of significant differences in group means. Multivariate analysis of the complete sphingolipidome provided the highest discriminatory power, distinguishing exposed from unexposed turkeys and chickens for up to four days after withdrawal of the FDZ diet. Finally, the biological significance of alterations in d18:1P, 18:0/2:0, 18:1/16:0, and dihydrosphingolipids induced by the FDZ diet is discussed. Full article

Chemical pollution from industrial, agricultural, and urban activities represents a major threat to freshwater ecosystems and aquatic organisms. This study evaluated hepatic biomarker responses in Oreochromis niloticus (Nile tilapia) maintained under chronic environmental exposure to water from the Iguaçu River, one of the most polluted urban rivers in Brazil. Juvenile fish were kept in cages at three sites along the river, and hepatic biomarkers were assessed after 15 and 22 months of environmental exposure. Fish showed severe histopathological liver lesions, activation of antioxidant defenses, and oxidative stress responses accompanied by increased DNA damage. Immunological responses, particularly melanomacrophage proliferation and granuloma formation, were also observed across the monitored exposure scenarios. Alterations in plasma biochemical parameters, including AST, ALT, LDH, albumin, and globulin, were consistent with changes in hepatic function. Overall, the integrated biomarker responses revealed distinct patterns of biological alteration among the monitored exposure scenarios and were consistent with chronic exposure to complex environmental contaminant mixtures. These findings are consistent with alterations in liver integrity in fish maintained under long-term environmental exposure in the Iguaçu River. The study highlights the sensitivity of Nile tilapia as a bioindicator species for aquatic biomonitoring and provides valuable information to support environmental monitoring, risk assessment, and conservation strategies for the Iguaçu River Basin. Full article

Background: Acute alcohol intoxication causes liver injury and delays recovery via oxidative stress, ferroptosis, inflammation, and gut dysbiosis. This study investigated whether pretreatment with an Alcohol Relief Formula (ARF), composed of soybean peptides, botanical extracts, and probiotics, protects against alcohol-induced liver damage in a preventive model and explored the underlying mechanisms. Methods: Mice with acute alcohol intoxication were pretreated with ARF. Liver damage, hepatic alcohol-metabolizing enzymes, antioxidant capacity, inflammatory cytokines, and lipid peroxidation were measured. Ferroptosis markers and AMP-activated protein kinase (AMPK) signaling were assessed. Gut microbiota composition and cecal short-chain fatty acids (SCFAs) were analyzed. Correlations between SCFAs, ferroptosis suppression, and AMPK activation were evaluated. Results: ARF pretreatment alleviated acute liver damage and accelerated sobriety. It enhanced alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH) activities, inhibited CYP2E1 expression, and improved alcohol metabolism. ARF pretreatment restored antioxidant capacity, decreased pro-inflammatory cytokines and lipid peroxidation, and ameliorated hepatic histopathological changes. Notably, ARF pretreatment was associated with suppressed ethanol-induced ferroptosis markers, including increased glutathione peroxidase 4 (GPX4), solute carrier family 7 member 11 (SLC7A11), and ferroptosis suppressor protein 1 (FSP1) expression, elevated AMPK phosphorylation, and reduced hepatic total iron content. In parallel, ARF pretreatment was associated with modulation of the alcohol-disrupted gut microbiota, increased short-chain fatty acid (SCFA)-producing bacteria, and maintained cecal acetate, propionate, and butyrate levels. Correlation analysis revealed that SCFA restoration was positively associated with ferroptosis marker modulation and AMPK activation, suggesting a potential link between gut metabolites and hepatic protection. Conclusions: ARF may serve as a potential preventive nutritional strategy for acute alcohol intoxication by promoting recovery and mitigating liver damage in this acute binge pretreatment model. The observed effects may involve the modulation of gut microbiota-derived SCFAs and AMPK signaling associated with ferroptosis markers. Full article

Objective: This research examined the effectiveness of liposomal N-Curcumin (N-Cur) against Cis-diamminedichloroplatinum (CDDP)-induced hepatotoxicity, specifically examining its ability to influence the Wnt/β-catenin/GSK-3 pathway and associated molecular markers. Methods: Male Wistar rats were treated for 14 days with oral N-Cur (80 mg/kg) and with a single intraperitoneal dose of CDDP (7 mg/kg) administered on day 7. Hepatic integrity was assessed through liver injury markers, histopathological examination, and biochemical analysis of oxidative stress (SOD, GSH, and MDA), inflammation (IL-10, TNF-α, CRP, and NF-κB p65), and signaling protein expression (β-catenin, Nrf2, and GSK-3). Results: CDDP administration resulted in significant hepatic damage, characterized by elevated injury markers and distorted tissue architecture. It induced severe oxidative stress (increased MDA; decreased GSH and SOD) and a robust inflammatory response. At the molecular level, CDDP suppressed the cytoprotective β-catenin and Nrf2 pathways while increasing GSK-3. Conversely, N-Cur treatment effectively reversed these pathological shifts by restoring antioxidant defenses, inhibiting pro-inflammatory mediators, and normalizing the Wnt/β-catenin/GSK-3 signaling axis. Conclusions: Liposomal N-Cur demonstrates significant potential as a hepatoprotective agent when administered concomitantly with CDDP chemotherapy. N-Cur mitigates oxidative damage and inflammation, thereby preserving hepatic function during CDDP-based chemotherapy. In addition, these favorable effects were associated with modulation of the Wnt/β-catenin/GSK-3 and Nrf2 pathways. Full article