C
ISPLATIN, a cornerstone chemotherapeutic agent, is significantly limited by dose-dependent
hepatorenal toxicity. This study comprehensively evaluated cisplatin-induced hepatorenal injury
in a rat model using 5, 7, and 10 mg/kg doses, with biochemical, oxidative stress, and
histopathological analyses at 3 and 5 days post-treatment. Liver toxicity manifested as dose- and time
dependent elevations in serum ALT and AST at 10 mg/kg by Day 5, correlating with histopathological
evidence of hepatocellular necrosis, inflammatory infiltrates, and portal fibrosis. Oxidative stress in
the liver was marked by increased lipid peroxidation and a compensatory but insufficient antioxidant
response. Conversely, renal toxicity exhibited distinct oxidative dynamics, with elevated MDA and
significant SOD depletion, indicating compromised antioxidant defenses. Renal dysfunction was
evidenced by dose-dependent increases in serum creatinine and urea alongside histopathological
findings of tubular necrosis, interstitial inflammation, and fibrosis. Histopathological scoring
confirmed progressive injury, with hepatocellular damage and tubular necrosis peaking at 10 mg/kg by
Day 5. Immunohistochemical analysis revealed heightened caspase-3 and TNF-α expression,
implicating oxidative stress-mediated apoptosis and inflammation as central mechanisms. These
findings highlight organ-specific antioxidant responses, with hepatic SOD activity transiently
countering oxidative stress, while renal SOD depletion exacerbated damage. The temporal and dose
dependent progression of injury underscores the need for rigorous clinical monitoring and adjunct
therapies, such as antioxidants or targeted drug delivery, to mitigate cisplatin’s toxicity without
compromising its antitumor efficacy. This study provides critical insights into the mechanistic
interplay of oxidative stress and organ damage, informing strategies to enhance therapeutic safety in
oncology. |
