Chrysin attenuates pentadecafluorooctanoic acid-induced hepatotoxicity in male Wistar rats via modulation of oxidative stress, inflammation, and metabolic dysfunction

Evaluation of the nephroprotective potential of chrysin against pentadecafluorooctanoic acid-induced kidney dysfunction in male Wistar rats

   Pentadecafluorooctanoic acid (PFOA) is a highly persistent environmental contaminant known for its bioaccumulative nature and ability to cause adverse renal effects. Prolonged exposure to PFOA has been associated with oxidative stress, inflammation, and membrane dysfunction, which collectively contribute to renal impairment. This study investigates the nephroprotective effects of chrysin, a naturally occurring flavonoid with potent antioxidant and anti-inflammatory properties, against PFOA-induced kidney toxicity in male Wistar rats. Twenty-five rats were divided into five groups (n = 5 per group): (i) control (20% dimethyl sulfoxide), (ii) PFOA-only (5 mg/kg), (iii) 25 mg/kg chrysin + 5 mg/kg PFOA, (iv) 50 mg/kg chrysin + 5 mg/kg PFOA, and (v) 50 mg/kg chrysin-only. All treatments were administered orally for 14 consecutive days. Exposure to PFOA resulted in a significant (p < 0.05) elevation in serum creatinine, lactate dehydrogenase, and electrolyte imbalances, accompanied by reduced antioxidant enzyme activities, elevated oxidative stress markers, increased inflammatory cytokines, and disrupted ATPase activity. Chrysin pre-treatment at both 25 and 50 mg/kg markedly attenuated these toxic effects in a dose-dependent manner. It restored antioxidant defenses, normalized biochemical indices, improved electrolyte balance, and suppressed inflammation, thereby preserving renal function. These findings suggest that chrysin confers significant nephroprotective effects against PFOA-induced renal injury by mitigating oxidative stress, inflammation, and ion transport disruption, supporting its therapeutic potential as a promising nephroprotective agent for protecting against environmentally induced kidney injury.

Pentoxifylline mitigates CCl4-induced liver damage in rats: integrated biochemical, hematological, histopathological, and correlation heatmap analysis

Abstract Pentoxifylline (PTX), a methylxanthine-derived phosphodiesterase inhibitor, has demonstrated anti-inflammatory and hepatoprotective potential. This study evaluated the effects of PTX on carbon tetrachloride (CCl4)-induced liver injury in rats, with clear differentiation between treatment conditions. Sixty Wistar rats were allocated into four groups: control, CCl4-only, PTX-only, and CCl4 followed by PTX (post-treatment model). CCl4 (1 mL/kg, i.p.) induced hepatic injury, while PTX was administered orally (50 mg/kg/day) for seven consecutive days either alone or after CCl4 exposure. CCl4 administration resulted in significant hepatotoxicity, evidenced by elevated serum ALT, AST, and LDH levels (p < 0.001), along with marked reductions in hepatic antioxidant markers (GSH, GPX, and CAT; p < 0.001), and alterations in organ weights and hematological parameters. PTX administered after CCl4 significantly ameliorated liver injury, as demonstrated by reductions in ALT (66.3 U/L, p < 0.001) and AST (184.7 U/L, p < 0.001), and restoration of antioxidant defenses, including GSH (6.70 µmol/g, p < 0.001). In contrast, PTX administered alone did not enhance antioxidant status and was associated with reductions in GSH, GPX, and CAT compared to control (p < 0.05), indicating that its protective effects are context-dependent. Correlation heatmap analysis revealed strong associations between liver enzymes and oxidative stress markers, supporting the mechanistic link between hepatocellular damage and redox imbalance. Hematological alterations induced by CCl4, including monocytosis and neutropenia, were partially normalized following PTX post-treatment. Histopathological findings corroborated the biochemical results, showing improved hepatocyte architecture and reduced inflammatory infiltration in PTX-treated rats. These findings suggest that PTX exerts significant hepatoprotective effects when administered after toxic insult, likely through modulation of oxidative stress and inflammation. Further studies are warranted to optimize dosing strategies and clarify its therapeutic window.

Protective effects of Rosmarinus officinalis against methotrexate-induced hepatorenal toxicity in Wistar rats: Biochemical, histopathological, and immunohistochemical evaluation

Background: Methotrexate (MTX) is one of the most frequently used chemotherapeutic and immunosuppressive agents; however, its clinical use is limited to hepatotoxicity and other organ toxicities associated with oxidative stress and inflammatory responses. Aim: The current study was conducted to evaluate the potential protective effect of the ethanolic extract of Rosmarinus officinalis against MTX-induced hepatorenal injury in Wistar rats. Methods: Hepatorenal toxicity was induced in Wistar rats via a single intraperitoneal administration of MTX (20 mg/kg). Rosemary extract was orally administered at doses of 100 and 200 mg/kg body weight. Liver function biomarkers (alanine aminotransferase, aspartate aminotransferase, and alkaline phosphatase), renal function parameters (urea and creatinine), and hematological indices were determined alongside oxidative stress markers (superoxide dismutase, catalase, glutathione peroxidase, glutathione, and Malondialdehyde) and levels of tumor necrosis factor-alpha (TNF-α). Hem atoxylin and eosin staining and immunohistochemical profiling were used for histopathological evaluation. Results: MTX caused a significant increase in liver enzymes, oxidative markers, and TNF-α while lowering antioxidant defenses. Histopathological examination revealed hepatocyte degeneration, vascular congestion, and inflammatory infiltration. Treatment with R. officinalis extract alleviated these changes in a dose-dependent manner, resulting in improved biochemical parameters and reduced tissue injury. Conclusion: Rosmarinus officinalis extract may exert protective effects against MTX-induced hepatorenal injury through antioxidant and anti-inflammatory mechanisms. However, further studies are required to confirm these effects and validate their therapeutic potential.

Mangiferin mitigates mercuric chloride-induced hepatotoxicity: targeting Nrf2, NF-κB, NLRP3, and ER stress.

Eugenol attenuates paraquat-induced hepatic and renal biomarker dysregulation in wistar rats: a dose-dependent protective assessment

Paraquat is a toxic herbicide, posing a severe health risk at minimal exposure. This experiment evaluated the efficacy of eugenol on PQ-dysregulation of hepato-renal biomarkers in Wistar rats. 32 Wistar rats from the AE-FUNAI animal house were acclimatized for 14 days and divided into four groups of 8 rats per Group. Group A served as normal control, while Groups B, C, and D received 10 mg/kg of paraquat for 28 days at one-day intervals. Group C and D were later treated with 300 mg/kg and 600 mg/kg of eugenol, respectively, for 14 days. After sacrifice, the liver and kidneys were harvested. A lobe of the liver and one of the kidneys were removed and homogenized separately to estimate hepato-renal biomarkers such as creatinine, urea, cystatin, phosphatase, amino acid-leucine, β-trace protein, albumin, alanine aminotransferase (ALT), alkaline phosphatase (ALP), aspartate aminotransferase (AST), Total protein (TP), lactate dehydrogenase (LDH), bicarbonate and prothrombin time (PrT). Paraquat significantly increased LDH, PrT, ALT, β-trace protein, cystatin, leucine and ALP while lowering AST, albumin, creatinine, urea, phosphatase, bicarbonate and TP (p<0.05). In the eugenol group, ALT decreased at 600 mg, ALP increased at 300 mg, AST increased at 600 mg relative to 300 mg, albumin and TP increased at 600 mg, LDH decreased at 600 mg relative to 300 mg, creatinine and urea increased at 600 mg relative to 300 mg, Cystatin and β-trace protein decreased at 600 mg relative to 300 mg, phosphate and HCO₃⁻ increased at 600 mg relative to 300 mg, and amino acid-leucine decreased at 300 mg (p<0.05). These findings show that eugenol is very efficacious against paraquat-induced hepato-renal toxicity that leads to the dysregulation of biomarkers.

Dexpanthenol Attenuates High-Fructose Corn Syrup-Induced Hepatic Injury in Young Adult Rats by Modulating Oxidative Stress, Apoptosis, and Inflammasome-Associated Pyroptotic Signaling

Excessive intake of high-fructose corn syrup (HFCS) contributes to pediatric metabolic dysfunction-associated steatotic liver disease, but the mechanisms linking fructose exposure to inflammatory cell death remain incompletely defined. This study investigated whether dexpanthenol (DEX) attenuates HFCS-induced liver injury by modulating oxidative stress, apoptosis, and nucleotide-binding domain-like receptor protein 3 (NLRP3) inflammasome-associated pyroptotic signaling. Thirty-two young adult male Wistar rats were assigned to control, HFCS, HFCS+DEX, and DEX groups (n = 8 each). HFCS-induced liver injury was established with 20% HFCS-55 in drinking water for 8 weeks. DEX (500 mg/kg/day, intraperitoneally) was administered from the end of week 4 to week 8. Liver tissues were assessed by histopathology; immunohistochemistry for caspase-3, malondialdehyde, and proliferating cell nuclear antigen; biochemical measurement of total antioxidant and oxidant status; and RT-qPCR analysis of Nlrp3, caspase-1, gasdermin D, and interleukin-1β. HFCS exposure caused steatosis, inflammation, and necrosis; increased histopathological scores; enhanced caspase-3, malondialdehyde, and proliferating cell nuclear antigen expression; elevated total oxidant status; and markedly upregulated inflammasome-related genes. Total antioxidant status did not differ among groups. DEX significantly improved hepatic architecture; reduced immunohistochemical markers of oxidative stress, apoptosis, and injury-associated proliferation; and downregulated NLRP3, caspase-1, gasdermin D, and interleukin-1β expression. These findings suggest that DEX attenuates HFCS-induced liver injury through a multi-target mechanism involving suppression of oxidative damage, apoptosis, and inflammasome-associated pyroptotic signaling in young adult rats.