Luteolin Mitigates Oxidative and Inflammatory Processes in Hepato-Renal Tissues of Rats Treated with Diethylnitrosamine and Carbon Tetrachloride

Hepatoprotective effects of diosgenin and gallic acid against chemical-induced liver injury in rats

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.

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

Pentadecafluorooctanoic acid (PFOA), a persistent environmental pollutant, has been implicated in hepatotoxicity through mechanisms involving oxidative stress, inflammation, and metabolic dysfunction. This study investigated the hepatoprotective effects of chrysin against PFOA-induced liver injury in male Wistar rats. Twenty-five male Wistar rats were randomly divided into five groups (n = 5): control (20% dimethyl sulfoxide), PFOA (5 mg/kg), PFOA + chrysin (25 mg/kg), PFOA + chrysin (50 mg/kg), and chrysin only (50 mg/kg). Treatments were orally administered for 14 days. Serum and hepatic biomarkers of liver function, oxidative stress, inflammation, membrane integrity, and energy metabolism were evaluated using standard biochemical assays and enzyme-linked immunosorbent assay methods. PFOA exposure significantly (p < 0.05) increased serum liver enzymes (alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, and lactate dehydrogenase), lipid peroxidation marker (malondialdehyde), and pro-inflammatory cytokines (interleukin 1 beta and interferon gamma), while significantly reducing antioxidant parameters (glutathione, catalase, superoxide dismutase, glutathione peroxidase, and glutathione-S-transferase, nitric oxide (NO), and membrane-bound enzyme activities, including adenosine triphosphatase (ATPase), Ca2+/Mg2+ ATPase, and 5’-nucleotidase. Chrysin treatment at both 25 and 50 mg/kg significantly (p < 0.05) ameliorated these alterations in a dose-dependent manner, with the 50 mg/kg dose showing greater protective efficacy. The findings indicate that PFOA-induced hepatotoxicity is associated with oxidative stress, inflammation, and metabolic dysfunction, whereas chrysin pre-treatment restores antioxidant defenses, attenuates inflammatory responses, and normalizes membrane-associated enzyme activities. Overall, chrysin demonstrates potent protective potential against PFOA-induced liver injury and may serve as a promising therapeutic candidate for environmental toxin-associated hepatotoxicity.

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.

Pharmacodynamics and pharmacokinetics of a novel phenolic hepatoprotective agent following single and multiple oral administration to healthy and liver-injured rats

Abstract Antioxidants play a crucial role in the treatment of liver pathologies, given that oxidative stress is involved in the pathogenesis of many hepatic diseases. This study aimed to investigate the pharmacodynamic and pharmacokinetic properties of the antioxidant 2,6-diisobornyl-4-methylphenol (IBP) in a rat model of carbon tetrachloride (CCl4)-induced liver injury. The introduction of IBP resulted in a 1.4- to 2-fold decrease in serum hepatic enzyme levels, a 25% and 18% rise in glutathione peroxidase and superoxide dismutase concentrations, respectively, and a 14% reduction in hepatic catalase activity compared with the negative control. Treated animals exhibited a 45% reduction in malondialdehyde (a marker of oxidative stress) and an 18% decrease in interleukin-6 levels relative to controls. The compound mitigated CCl4-induced liver damage and promoted restoration of liver function. Liver pathology affected the plasma exposure of IBP after a single administration, but pharmacokinetics normalized following repeated dosing. Bioavailability was 60% after a single dose and increased to 119% after multiple administrations. IBP demonstrated significant hepatoprotective effects in CCl4-induced liver injury, mitigating lipid peroxidation, inflammation, and necrosis. The initial reduction in systemic exposure following a single dose in pathological conditions may be attributed to impaired absorption and elevated metabolic consumption due to oxidative stress.

Ameliorative Effects of Ginkgo biloba on Lead Acetate-Induced Oxidative Stress and Histopathological Damages in Rat Liver, Kidney, and Testis.

Ginkgo biloba is a nutritional supplement known for its antioxidant properties and beneficial effects on different organs. This study aimed to investigate the protective effect of Ginkgo biloba supplementation against acute lead toxicity in rats. Thirty-two male Wistar rats were divided into four groups and treated daily for 7 days. The control group received normal saline (1 mL/day, orally). The model group received lead acetate (50 mg/kg/day, ip) without any treatment, and the model with either ethylenediaminetetraacetic acid (EDTA) (50 mg/kg/day, ip) or Ginkgo biloba (200 mg/kg/day, oral gavage). After 7 days, blood samples were collected, and livers, kidneys, and testes were excised and stored for evaluation of oxidative stress markers and histological assessment. Acute lead acetate administration resulted in significant weight loss, an increase in kidney index, elevated serum creatinine and liver enzyme levels, including serum glutamic oxaloacetic transaminase (SGOT), serum glutamic-pyruvic transaminase (SGPT), and alkaline phosphatase (AlkP), and extensive histological damage in the liver, kidney, and testicular tissues. Administration of the Ginkgo biloba significantly improved serum creatinine and AlkP, showing greater efficacy than EDTA, and reduced histopathological changes, similar to EDTA, including hepatic vascular congestion and fibrosis, renal dilation of Bowman spaces, and glomerular degeneration. Furthermore, Ginkgo biloba treatment improved Leydig and spermatogonia cell counts. Both Ginkgo biloba and EDTA reduced malondialdehyde (MDA) levels and enhanced superoxide dismutase (SOD) and catalase activities in these organs. Ginkgo biloba exhibited protective effects against lead-induced hepatic, renal and testicular damage through its ability to reduce oxidative stress damage. These results indicate that Ginkgo biloba may serve as a valuable adjunct therapy for mitigating lead-associated organ damage.