Search Results (30)

Acetaminophen (APAP) overdose is a major cause of acute liver failure and can be fatal, often without early symptoms. Protein deficiency, arising from illness or inadequate diet, impairs growth, immunity, and tissue repair. Both conditions can harm the kidneys, yet the impact of energy imbalance on renal physiology remains unclear. In this study, APAP toxicity and a low-protein diet induced behavioral suppression and tissue damage, as evidenced by reduced whole-body, liver, and kidney weights in rats. In kidney mitochondria of rats exposed to only toxic APAP doses, ATP levels declined sharply while ADP and AMP increased. AMP deaminase and ATPases’ activities rose about twofold and 1.5-fold, respectively, whereas cytosolic 5′-nucleotidase activity fell nearly threefold, suggesting compensatory responses to disrupted energy balance. The strongest reductions in ATP and the greatest increases in AMP and ATPase activity occurred in APAP-intoxicated rats fed a low-protein diet. This combination also intensified lipid peroxidation and oxidative protein damage, evidenced by elevated TBARS, reduced protein SH-groups, and increased protein carbonyls. Overall, APAP intoxication with protein deficiency disrupts renal energy metabolism, leading to mitochondrial dysfunction and structural kidney injury. Nutritional status therefore critically influences drug-induced nephrotoxicity, and antioxidant strategies may help prevent damage under metabolic stress. Full article

Jaboticaba (Plinia cauliflora), a Brazilian native fruit rich in bioactive compounds, exhibits potent anti-inflammatory and antioxidant properties. This pilot study evaluated the effects of jaboticaba peel supplementation on inflammatory and oxidative stress markers and uremic toxins among patients with chronic kidney disease (CKD) undergoing hemodialysis (HD) and explored its molecular effects in LLC-PK1 renal cells. A randomized, controlled clinical trial was conducted with 27 patients (55.0 [19.5] years, BMI 24.3 [3.8] kg/m²) on regular HD. Participants were allocated to receive the jaboticaba peel formulation (3.3 g/day, equivalent to ~667 mg of phenolic compounds) for 3 weeks or to routine treatment (control). Plasma levels of interleukin (IL)-1β and IL-17E (ELISA), lipid peroxidation (TBARS), protein carbonylation, and plasma levels of uremic were analyzed. LLC-PK1 cells were treated with 100 µL of jaboticaba peel formulation at different concentrations, and a panel of inflammatory genes was evaluated. While plasma IL-1β and IL-17E concentrations were increased in the control group, the jaboticaba group exhibited no significant changes, suggesting anti-inflammatory protection. Transcriptomic analysis revealed downregulation of key components of the TLR–MYD88–NF-κB–IL-1 axis after cell treatment. Additionally, cells treated with jaboticaba formulation (1.5%) showed reduced ROS levels, indicating antioxidant capacity. In conclusion, supplementation with jaboticaba peel attenuated the increase in pro-inflammatory markers in HD patients. These results suggest that jaboticaba peel holds promise as an adjuvant nutritional intervention for chronic inflammation in CKD. Full article

Oxidative stress plays a crucial role in disease pathogenesis. While reactive oxygen species (ROS) directly cause cellular injury, emerging evidence suggests oxidatively modified proteins like albumin may also contribute significantly to tissue damage. Although oxidized albumin (ox-Alb) is linked to renal pathology, the direct effects and mechanisms of ox-Alb on renal cell injury remain unclear. This study was created to address these questions. In mouse models of renal injury initiated by vitamin C/copper or ischemia/reperfusion, levels of serum ox-Alb were significantly elevated. The treatment of albumin with copper/vitamin C increased Alb carbonylation and reduced the number of sulfhydryl groups, causing Alb oxidation. In cultured renal tubular epithelial NRK-52E cells, ox-Alb triggered cell death, associated with increased intracellular albumin accumulation—enhanced cellular protein carbonylation, and p38 MAPK activation. Notably, ox-Alb induced ferroptosis, evidenced by decreased GPX4 and xCT, increased ACSL4, elevated iron and lipid peroxidation, and suppression by deferoxamine and liproxstatin-1. In vivo, administration of ox-Alb exacerbated doxorubicin-induced nephropathy, as indicated by the elevated BUN, creatinine, and proteinuria, and intensified renal ferroptotic responses, including altered GPX4 and ACSL4. Our findings demonstrate that ox-Alb induces renal cell ferroptosis and promotes renal disease progression, suggesting its pivotal pathogenic role in oxidative stress-related kidney diseases. Full article

Advanced glycation end products (AGEs) represent a class of toxic and irreversible compounds formed through non-enzymatic reactions between proteins or lipids and carbonyl compounds. AGEs can arise endogenously under normal metabolic conditions and in pathological states such as diabetes, kidney disease, and inflammatory disorders. Additionally, they can be obtained exogenously through dietary intake, particularly from foods high in fat or sugar, as well as grilled and processed items. AGEs accumulate in various organs and have been increasingly recognized as significant contributors to the progression of numerous diseases, particularly kidney disease. As the kidney plays a crucial role in AGE metabolism and excretion, it is highly susceptible to AGE-induced damage. In this review, we provide a comprehensive discussion on the role of AGEs in the onset and progression of various kidney diseases, including diabetic nephropathy, chronic kidney disease, and acute kidney injury. We explore the potential biological mechanisms involved, such as AGE accumulation, the AGEs-RAGE axis, oxidative stress, inflammation, gut microbiota dysbiosis, and AGE-induced DNA damage. Furthermore, we discuss recent findings on the metabolic characteristics of AGEs in vivo and their pathogenic impact on renal function. Additionally, we examine the clinical significance of AGEs in the early diagnosis, treatment, and prognosis of kidney diseases, highlighting their potential as biomarkers and therapeutic targets. By integrating recent advancements in AGE research, this review aims to provide new insights and strategies for mitigating AGE-related renal damage and improving kidney disease management. Full article

Background: Hypertension is a major cause of mortality worldwide. The kidneys play a crucial role in regulating blood pressure and fluid volume. The relationship between the kidneys and hypertension is complex, involving factors such as the renin–angiotensin system, oxidative stress, and inflammation. This study aims to assess the levels of inflammatory markers, oxidative stress, and metabolic factors in the kidneys, focusing on their potential role in early renal damage and their association with the development of hypertension. Methods: This study was designed to compare the levels of selected inflammatory markers, e.g., interleukins, tumor necrosis factor-α (TNF-α), transforming growth factor, and serine/threonine-protein (mTOR); oxidative stress markers such as malondialdehyde, sulfhydryl group, and glucose (GLC); and metabolic markers among other enzymes, such as alanine transaminase (ALT), aspartate transaminase (AST), hexokinase II (HK-II), and hypoxia-inducible factor-1α (HIF-1α), as well as creatinine in the kidneys of spontaneously hypertensive rats (SHR/NCrl, n = 12) and Wistar Kyoto rats (WKY/NCrl, n = 12). Both juvenile (5 weeks old) and maturing (10 weeks old) specimens were examined using spectrophotometric methods, e.g., ELISA. Results: Juvenile SHRs exhibited reduced renal levels of all studied cytokines and chemokines, with lower oxidative stress and deficits in the mTOR and HK-II levels compared to the age-matched WKYs. Maturing SHRs showed increased renal levels of interleukin-1β (IL-1β), IL-6, IL-18, and TNF-α, alongside elevated carbonyl stress and increased HIF-1α as opposed to their control peers. The levels of all other studied markers were normalized in these animals, except for ALT (increased), ALP, and GLC (both reduced). Conclusions: This study underscores the significant impact of inflammatory, oxidative stress, and metabolic marker changes on renal function. Juvenile SHRs display lower marker levels, indicating an immature immune response and potential subclinical kidney damage that may contribute to hypertension development. In contrast, mature SHRs exhibit chronic inflammation, oxidative dysregulation, and metabolic disturbances, suggesting cellular damage. These changes create a feedback loop that worsens kidney function and accelerates hypertension progression, highlighting the kidneys’ crucial role in both initiating and exacerbating this condition. Full article

Cyclophosphamide (CPA) is an alkylating agent used as a chemotherapy agent in the treatment of cancer, but it has immunosuppressive effects. Protium heptaphyllum (P. heptaphyllum) is a plant rich in triterpenes and flavonoids, with some bioactive and therapeutic properties presented in the literature. Thus, the present study aimed to investigate the chemoprotective potential of P. heptaphyllum extract inserted into liposomes against oxidative damage chemically induced by CPA. Male Swiss mice received 1.5 mg/kg of P. heptaphyllum liposomes as a pre-treatment for 14 consecutive days (via gavage) and 100 mg/kg of CPA in a single dose (via intraperitoneal) on the 15th day. After the experimental period, blood and organ samples were collected for histopathological and biochemical analyses, including superoxide dismutase (SOD), glutathione peroxidase (GPx), catalase (CAT), glutathione S-transferase (GST), reduced glutathione (GSH), thiobarbituric acid reactive substances (TBARS), ascorbic acid (ASA), carbonyl protein, cytokine measurement, and micronucleus testing. The results showed that liposomes containing P. heptaphyllum extract have an antimutagenic effect against damage induced to DNA by CPA, and that they also protect against oxidative stress, as verified by the increase in the antioxidant enzymes SOD and GPx. The improvement in alkaline phosphatase and creatinine markers suggests a beneficial effect on the liver and kidneys, respectively. However, the depletion of GSH in the liver and brain suggests the use of antioxidants for the metabolism of molecules generated in these tissues. In general, these data show good prospects for the use of P. heptaphyllum liposomes as a cancer chemoprotective agent, as well as possible antioxidant action, conceivably attributed to the flavonoids present in the plant extract. Full article

The aim of this study was the investigation of biochemical and histological changes induced in different tissues, as a result of the subcutaneous administration of Gd nanohydrogels (GdDOTA⸦CS-TPP/HA) in a CD-1 mouse strain. The nanohydrogels were obtained by encapsulating contrast agents (GdDOTA) in a biocompatible polymer matrix composed of chitosan (CS) and hyaluronic acid (HA) through the ionic gelation process. The effects of Gd nanohydrogels on the redox status were evaluated by measuring specific activities of the antioxidant enzymes catalase (CAT), glutathione peroxidase (GPx), and superoxide dismutase (SOD), as well as oxidative stress markers, such as reduced glutathione (GSH), malondialdehyde (MDA), advanced oxidation protein products (AOPP), and protein-reactive carbonyl groups (PRCG), in the liver, kidney, and heart tissues. The nitrosylated proteins expression were analyzed with Western Blot and the serum biochemical markers were measured with spectrophotometric methods. Also, a histological analysis of CD-1 mouse tissues was investigated. These results indicated that Gd nanohydrogels could potentially be an alternative to current MRI contrast agents thanks to their low toxicity in vivo. Full article

In the present study, an attempt was made to investigate the in vitro antioxidant, anticancer, and antibacterial activities of Delonix regia, then in vivo evaluate its safety as a natural colorant and sweetener in beverages compared to synthetic colorant and sweetener in rats, then serve the beverages for sensory evaluation. Delonix regia flowers had high protein, polysaccharide, Ca, Na, Mg, K, and Fe contents. The Delonix regia pigment extract (DRPE) polysaccharides were separated and purified by gel permeation chromatography on Sephacryl S-200, characterized by rich polysaccharides (13.6 g/L). The HPLC sugar profile detected the monosaccharides in the extracted polysaccharides, composed of mannose, galactose, glucose, arabinose, and gluconic acid, and the structure of saccharides was confirmed by FTIR, which showed three active groups: carbonyl, hydrocarbon, and hydroxyl. On the other hand, the red pigment constituents of DRPE were detected by HPLC; the main compounds were delphinidin and cyanidin at 15 µg/mL. The DRPE contained a considerable amount (26.33 mg/g) of anthocyanins, phenolic compounds (64.7 mg/g), and flavonoids (10.30 mg/g), thus influencing the antioxidant activity of the DRPE, which scavenged 92% of DPPH free radicals. Additionally, it inhibited the population of pathogenic bacteria, including Staphylococcus aureus, Listeria monocyogenes, Salmonella typhimurum, and Pseudomonas aeruginosa, in the range of 30–90 μg/mL, in addition to inhibiting 85% of pancreatic cancer cell lines. On the in vivo level, the rats that were delivered a diet containing DRPE showed regular liver markers (AST, ALP, and ALT); kidney markers (urea and creatinine); high TP, TA, and GSH; and low MDA, while rats treated with synthetic dye and aspartame showed higher liver and kidney markers; lowered TP, TA, and GSH; and high MDA. After proving the safety of DRPE, it can be safely added to strawberry beverages. Significant sensorial traits, enhanced red color, and taste characterize the strawberry beverages supplemented with DRPE. The lightness and redness of strawberries were enhanced, and the color change ΔE values in DRPE-supplemented beverages ranged from 1.1 to 1.35 compared to 1.69 in controls, indicating the preservative role of DRPE on color. So, including DRPE in food formulation as a natural colorant and sweetener is recommended for preserving health and the environment. Full article

Obesity has been recognized as a major risk factor for chronic kidney disease, insulin resistance being an early common metabolic feature in patients suffering from this syndrome. This study aims to investigate the mechanism underlying the induction of kidney dysfunction and the concomitant onset of insulin resistance by long-term high-fat and sucrose diet feeding in Sprague Dawley rats. To achieve this goal, our study analyzed renal carbonylated protein patterns, ectopic lipid accumulation and fatty acid profiles and correlated them with biometrical and biochemical measurements and other body redox status parameters. Rats fed the obesogenic diet developed a prediabetic state and incipient kidney dysfunction manifested in increased plasma urea concentration and superior levels of renal fat deposition and protein carbonylation. An obesogenic diet increased renal fat by preferentially promoting the accumulation of saturated fat, arachidonic, and docosahexaenoic fatty acids while decreasing oleic acid. Renal lipotoxicity was accompanied by selectively higher carbonylation of proteins involved in the blood pH regulation, i.e., bicarbonate reclamation and synthesis, amino acid, and glucose metabolisms, directly related to the onset of insulin resistance. This study also tested the combination of antioxidant properties of fish oil with the anti-diabetic properties of buckwheat D-Fagomine to counteract diet-induced renal alterations. Results demonstrated that bioactive compounds combined attenuated lipotoxicity, induced more favorable lipid profiles and counteracted the excessive carbonylation of proteins associated with pH regulation in the kidneys, resulting in an inhibition of the progression of the prediabetes state and kidney disease. Full article

This study addresses a joint nuclear magnetic resonance (NMR) and electron paramagnetic resonance (EPR) spectroscopy approach to provide a platform for dynamic assessment of kidney viability and metabolism. On porcine kidney models, ROS production, oxidative damage kinetics, and metabolic changes occurring both during the period between organ retrieval and implantation and after kidney graft were examined. The ¹H-NMR metabolic profile—valine, alanine, acetate, trimetylamine-N-oxide, glutathione, lactate, and the EPR oxidative stress—resulting from ischemia/reperfusion injury after preservation (8 h) by static cold storage (SCS) and ex vivo machine perfusion (HMP) methods were monitored. The functional recovery after transplantation (14 days) was evaluated by serum creatinine (SCr), oxidative stress (ROS), and damage (thiobarbituric-acid-reactive substances and protein carbonyl enzymatic) assessments. At 8 h of preservation storage, a significantly (p < 0.0001) higher ROS production was measured in the SCS vs. HMP group. Significantly higher concentration data (p < 0.05–0.0001) in HMP vs. SCS for all the monitored metabolites were found as well. The HMP group showed a better function recovery. The comparison of the areas under the SCr curves (AUC) returned a significantly smaller (−12.5 %) AUC in the HMP vs. SCS. EPR-ROS concentration (μmol·g⁻¹) from bioptic kidney tissue samples were significantly lower in HMP vs. SCS. The same result was found for the NMR monitored metabolites: lactate: −59.76%, alanine: −43.17%; valine: −58.56%; and TMAO: −77.96%. No changes were observed in either group under light microscopy. In conclusion, a better and more rapid normalization of oxidative stress and functional recovery after transplantation were observed by HMP utilization. Full article

Kidney diseases belong to a group of pathologies, which are most common among elderly people. With age, even outwardly healthy organisms start to exhibit some age-related changes in the renal tissue, which reduce the filtration function of kidneys and increase the susceptibility to injury. The therapy of acute kidney injury (AKI) is aggravated by the absence of targeted pharmacotherapies thus yielding high mortality of patients with AKI. In this study, we analyzed the protective effects of calorie restriction (CR) against ischemic AKI in senescence-accelerated OXYS rats. We observed that CR afforded OXYS rats with significant nephroprotection. To uncover molecular mechanisms of CR beneficial effects, we assessed the levels of anti- and proapoptotic proteins of the Bcl-2 family, COX IV, GAPDH, and mitochondrial deacetylase SIRT-3, as well as alterations in total protein acetylation and carbonylation, mitochondrial dynamics (OPA1, Fis1, Drp1) and kidney regeneration pathways (PCNA, GDF11). The activation of autophagy and mitophagy was analyzed by LC3 II/LC3 I ratio, beclin-1, PINK-1, and total mitochondrial protein ubiquitination. Among all considered protective pathways, the improvement of mitochondrial functioning may be suggested as one of the possible mechanisms for beneficial effects of CR. Full article

Diabetes is a long-term metabolic disorder characterized by persistently elevated blood sugar levels. Chronic hyperglycemia enhances glucose–protein interactions, leading to the formation of advanced glycation end products (AGEs), which form irreversible cross-links with a wide variety of macromolecules, and accumulate rapidly in the body tissues. Thus, the objective of this study was to assess the therapeutic properties of C-phycocyanin (C-PC) obtained from Plectonema species against oxidative stress, glycation, and type 2 diabetes mellitus (T2DM) in a streptozotocin (STZ)-induced diabetic Wistar rat. Forty-five days of C-PC administration decreased levels of triglycerides (TGs), blood glucose, glycosylated hemoglobin, (HbA1c), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), liver and kidney function indices, and raised body weight in diabetic rats. C-PC suppressed biochemical glycation markers, as well as serum carboxymethyllysine (CML) and fluorescent AGEs. Additionally, C-PC maintained the redox state by lowering lipid peroxidation and protein-bound carbonyl content (CC), enhancing the activity of high-density lipoprotein cholesterol (HDL-C) and renal antioxidant enzymes, and preserving retinal and renal histopathological characteristics. Thus, we infer that C-PC possesses antidiabetic and antiglycation effects in diabetic rats. C-PC may also act as an antidiabetic and antiglycation agent in vivo that may reduce the risk of secondary diabetic complications. Full article

Oxidative stress (OS) presents even in the early chronic kidney disease (CKD) stage and is exacerbated in patients with end-stage renal disease (ESRD) undergoing maintenance hemodialysis (MHD). There is still a debate over the association between oxidative stress and mortality. Our study aims to compare head-to-head the prognostic value of different oxidative markers for all-cause mortality in hemodialysis (HD) patients. We thus enrolled 347 patients on HD in this prospective study. Four OS biomarkers were measured (carbonyl proteins, myeloperoxidase (MPO), advanced oxidation protein products (AOPPs), and oxidized low-density lipoprotein (ox-LDL)). During the 60-month follow-up period, 9 patients have been lost to follow-up and 168 (48.4%) patients died. Concerning the oxidative stress (ox-stress) byproducts, carbonyl proteins were lower in survivors (105.40 ng/mL (IQR 81.30–147.85) versus 129.65 ng/mL (IQR 93.20–180.33); p < 0.001), with similar results for male patients (103.70 ng/mL (IQR 76.90–153.33) versus 134.55 ng/mL (IQR 93.95–178.68); p = 0.0014). However, there are no significant differences in MPO, AOPP, and ox-LDL between the two groups. Kaplan–Meier survival analysis indicated that patients in the higher carbonyl proteins concentration (>117.85 ng/mL group) had a significantly lower survival rate (log-rank test, p < 0.001). Univariate Cox regression analysis showed a positive correlation between carbonyl proteins and all-cause mortality in the higher and lower halves. Even after adjustment for conventional risk factors, it remained a statistically significant predictor of an increased risk of death in MHD. Univariate Cox regression analysis of MPO showed that continuous MPO and Log MPO were significantly associated with all-cause mortality, except for binary MPO (divided according to the median of MPO). Multivariate Cox analysis for MPO showed that the mortality prediction remains significant after adjusting for multiple factors. In conclusion, not all ox-stress biomarkers predict all-cause mortality in HD patients to a similar extent. In the present study, carbonyl proteins and MPO are independent predictors of all-cause mortality in HD patients, whereas AOPPs and oxLDL are clearly not associated with all-cause mortality in HD patients. Full article

The present study describes the green biofunctional synthesis of magnesium oxide (MgO) nanoparticles using the aqueous Tarenna asiatica fruit extract. The characterization of Tarenna asiatica fruit extract MgO nanoparticles (TAFEMgO NPs) was achieved by X-ray powder diffraction, UV-Vis spectroscopy, FTIR, TEM, SEM, and energy-dispersive X-ray diffraction. TAFEMgO NPs scavenged the DPPH free radicals with an IC50 value of 55.95 μg/μL, and it was highly significant compared to the standard. To authenticate the observed antioxidant potential of TAFEMgO NPs, oxidative stress was induced in red blood cells (RBC) using sodium nitrite (NaNO₂). Interestingly, TAFEMgO NPs ameliorated the RBC damage from oxidative stress by significantly restoring the stress parameters, such as the protein carbonyl content (PCC), lipid peroxidation (LPO), total thiol (TT), super-oxide dismutase (SOD), and catalase (CAT). Furthermore, oxidative stress was induced in-vivo in Sprague Dawley female rats using diclofenac (DFC). TAFEMgO NPs normalized the stress parameters in-vivo and minimized the oxidative damage in tissues. Most importantly, TAFEMgO NPs restored the function and architecture of the damaged livers, kidneys, and small intestines by regulating biochemical parameters. TAFEMgO NPs exhibited an anticoagulant effect by increasing the clotting time from 193 s in the control to 885 s in the platelet rich plasma. TAFEMgO NPs prolonged the formation of the clot process in the activated partial thromboplastin time and the prothrombin time, suggest the effective involvement in both intrinsic and extrinsic clotting pathways of the blood coagulation cascade. TAFEMgO NPs inhibited adenosine di-phosphate (ADP)-induced platelet aggregation. TAFEMgO NPs did not show hemolytic, hemorrhagic, and edema-inducing properties at the tested concentration of 100 mg/kgbody weight, suggesting its non-toxic property. In conclusion, TAFEMgO NPs mitigates the sodium nitrite (NaNO₂)- and diclofenac (DFC)-induced stress due to oxidative damage in both in vitro and in vivo experimental models. Full article

Opuntia stricta is a rich source of phenolic compounds. This species generally has strong antioxidant activities in vitro and in vivo. This study aimed to analyze the antioxidant properties of phenolic compounds isolated from Opuntia stricta, including its radical scavenging activities and preventive action against Cd-induced oxidative stress in rats. To assess the protection of prickly pear juice extract (PPJE) against Cd-induced hepato-nephrotoxicity and testicular damage, male albino rats received PPJE (250 mg kg⁻¹) and/or Cd (1 mg kg⁻¹) by oral administration and injection, respectively, for five consecutive weeks. The preventive action of PPJE was estimated using biochemical markers of kidney and liver tissues, antioxidant status, and histological examinations. In the present study, the lipid peroxidation, protein carbonyls, antioxidant status, and metallothionein levels were determined in different tissues. The chromatographic analysis indicated that PPJE extract is very rich in phenolic compounds such as verbascoside, catechin hydrate, and oleuropein. Our results showed that PPJE-treated rats had significantly (p < 0.05) decreased Cd levels in liver and kidney tissues. In addition, the administration of PPJE induced a significant (p < 0.05) decrease in lipid peroxidation of 30.5, 54.54, and 40.8 in the liver, kidney, and testicle, respectively, and an increase in antioxidant status in these tissues. Additionally, PPJE showed a strong ability to protect renal, hepatic, and testicular architectures against Cd exposure. This study revealed that PPJE protects against the toxic effects of Cd, possibly through its free radical scavenging and antioxidant activities. Full article