cisplatin, 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 reactive
changes. 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, with increased collagen
deposition. 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. |
