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

Rosemary (Rosmarinus officinalis) Extract Attenuates Methotrexate-Induced Oxidative Stress, Inflammatory Disturbance, and Apoptotic Lung Injury: A Molecular and Histopathological Study.

The potential therapeutic effect of quercetin on mitochondrial dysfunction in hepatorenal toxicity induced by aluminum chloride in an experimental rat model

Aluminum is a xenobiotic element known to induce hepatorenal toxicity through mechanisms involving mitochondrial dysfunction, oxidative stress, and inflammation. Quercetin, a dietary flavonoid with potent antioxidant and anti-inflammatory properties, has shown promise as a therapeutic agent. This study aimed to evaluate the potential therapeutic effects of quercetin against aluminum chloride (AlCl₃)-induced hepatorenal toxicity and mitochondrial dysfunction in rats. Hepatorenal toxicity was induced by oral administration of hydrated aluminum chloride (75 mg/kg body weight) daily for six weeks. Quercetin was administered intraperitoneally at a dose of 30 mg/kg body weight daily for four weeks. Biochemical assays, mitochondrial gene expression analysis, and histopathological examinations were conducted to assess the therapeutic effects. Quercetin significantly ameliorated lipid, protein, and DNA oxidation parameters (MDA, AOPPs and 8-OHdG respectively), reduced inflammation marker (TNF-α), and restored mitochondrial biogenesis markers, including PGC-1α, mtTFA and mitochondrial DNA copy number (mtDNA-CN). In addition, Quercetin significantly decreased TNF-α and increased PGC-1α contents at protein levels. Histopathological findings corroborated these results, demonstrating that quercetin improved liver and kidney architecture. These findings suggest that quercetin may serve as a potential therapeutic agent for aluminum-induced hepatorenal toxicity.

Evaluation of the Hepatoprotective Activity of Serinolamide A against Paracetamol-Induced Hepatotoxicity in Rats

Paracetamol-induced hepatotoxicity is characterized by oxidative stress, inflammatory responses, and progressive liver damage. The present study aimed to evaluate the hepatoprotective effects of Serinolamide A against paracetamol-induced hepatotoxicity in rats. Experimental hepatotoxicity was induced by paracetamol administration, and rats were treated orally with Serinolamide A (1, 5, and 10 mg/kg) for 28 consecutive days. Liv52 (70 mg/kg, p.o.) was used as the standard drug. Body weight, liver weight, serum biochemical parameters, oxidative stress markers, pro-inflammatory cytokines, and histopathological changes were evaluated. Treatment with Serinolamide A significantly ameliorated paracetamolinduced alterations and restored body and liver weights. Furthermore, Serinolamide A enhanced antioxidant defense by increasing superoxide dismutase, catalase, and reduced glutathione activities and reduced lipid peroxidation. The treatment also attenuated inflammatory responses by decreasing tumor necrosis factor-α and interleukin-6 levels. Histopathological examination revealed marked protection against paracetamol-induced hepatic damage. The observed effects were dose-dependent, with the 10 mg/kg dose showing effects comparable to those of Liv52. These findings suggest that Serinolamide A possesses significant hepatoprotective activity, which may be attributed to its antioxidant and anti-inflammatory properties, and could represent a promising therapeutic candidate for the management of drug-induced liver injury

The antioxidant, anti-inflammatory and anti-apoptotic effects of Cucumis melo var. agrestis Naudin in doxorubicin-induced hepatotoxicity and nephrotoxicity in rats

This study investigated the protective effects of Cucumis melo var. agrestis Naudin (CM) at various doses against doxorubicin-induced liver and kidney injury in rats. Thirty male Wistar rats were randomly divided into five groups (n = 6 per group). DOX was administered intraperitoneally at a dose of 15 mg/kg on day 5. CM was administered orally at doses of 100, 250 or 500 mg/kg daily for ten consecutive days after DOX administration. Histological and immunohistochemical analyses were performed to evaluate tissue damage and the expression levels of caspase-3, HSP70, NF-κB p65 and TNF-α. Serum cytokines (IL-6, IL-1β, TNF-α and IL-10) and oxidative stress markers (TOS and TAS) were also measured. The DOX group exhibited significant liver and kidney damage, including hepatocellular degeneration, vascular congestion, and injury to the glomeruli and tubules, as well as increased immunoreactivity for Caspase-3, HSP70, NF-κB-p65, and TNF-α. The DOX+CM250 group showed a significant improvement in histological appearance and a marked reduction in immunoreactivity. Compared to the DOX group, this group also demonstrated decreased levels of pro-inflammatory cytokines and TOS, and increased IL-10 and TAS levels. CM significantly attenuates DOX-induced hepatotoxicity and nephrotoxicity, particularly at a dose of 250 mg/kg. Its protective effects are likely mediated through antioxidant, anti-inflammatory, and anti-apoptotic mechanisms. Abbreviations: ALT – Alanine aminotransferase, AST – Aspartate aminotransferase, Bax – Bcl-2–associated X protein, Bcl-2 – B-cell lymphoma 2, BUN – Blood urea nitrogen, CM – Cucumis melo var. agrestis Naudin, DOX – Doxorubicin, GGT – Gamma-glutamyl transferase, GR – Glutathione reductase, GSH – Glutathione, HSP70 – Heat shock protein 70, IHC – Immunohistochemistry, IL – Interleukin, IL-1β – Interleukin-1 beta, IL-6 – Interleukin-6, IL-10 – Interleukin-10, MDA – Malondialdehyde, NF-κB – Nuclear factor kappa B, NF-κB p65 – Nuclear factor kappa B subunit p65, PCNA – Proliferating cell nuclear antigen, ROS – Reactive oxygen species, SOD – Superoxide dismutase, TAS – Total antioxidant status, TNF-α – Tumor necrosis factor alpha, TOS – Total oxidative status

Nicotinamide Riboside Attenuates Cisplatin-Induced Hepatorenal Toxicity Through Restoration of NAD+ Homeostasis and Nrf2/NQO1-Dependent Antioxidant Signaling

Nicotinamide riboside exerts protective effects against cisplatin-induced hepatorenal toxicity that are mechanistically linked to activation of the Nrf2/NQO1 antioxidant pathway and restoration of hepatic NAD+ homeostasis.

Comparative Hepatoprotective Effects of Carica papaya, Azadirachta indica, and Allium sativum Extracts against Diethyl Nitrosamine-Induced Liver Injury in Wistar Rats

It is indicated that combining papaya, neem, and garlic extracts may provide greater hepatoprotection than administering the individual extracts against DEN-induced liver injury, and supports further mechanistic and preclinical evaluation of this polyherbal formulation before its potential therapeutic application in liver-disease management.