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

Abstract

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