Morphological and Biochemical Changes in Rat Hippocampal Tissue Following Exposure to Different Doses of Cisplatin

Background/Objectives: Cisplatin (CP) is a platinum-based chemotherapeutic agent associated with neurotoxicity and cognitive impairment. Due to its high metabolic activity and sensitivity to oxidative stress, the hippocampus represents a particularly vulnerable brain structure. The present study evaluated dose-dependent hippocampal alterations following single-dose cisplatin administration in rats using biochemical, histopathological, and morphometric analyses. Methods: Male Wistar rats were divided into four groups (n = 8): control and cisplatin-treated groups receiving single intraperitoneal doses of 8, 9, or 10 mg/kg. Five days after treatment, hippocampal tissue was analyzed for oxidative stress and inflammatory, apoptotic, and morphological changes. Results: Cisplatin administration significantly increased TBARS and AOPP levels, indicating enhanced lipid and protein oxidation. Elevated hippocampal TNF-α, IL-6, and IL-1β levels demonstrated activation of inflammatory pathways, particularly in animals receiving 9 and 10 mg/kg cisplatin. Higher doses additionally increased Bax/Bcl-2 ratio, caspase-3 content, and DNase I/II activity, consistent with enhanced apoptotic signaling. Histopathological examination revealed neuronal degeneration, pyknotic nuclei, pericellular halo formation, and progressive disruption of hippocampal cytoarchitecture, while morphometric analysis demonstrated significant alterations in neuronal nuclear surface area, predominantly in the 10 mg/kg group. Conclusions: These findings demonstrate that acute cisplatin exposure induces oxidative, inflammatory, apoptotic, and structural progressive hippocampal injury with a threshold-like increase in several endpoints at higher cisplatin doses, with 10 mg/kg producing the most pronounced neurotoxic effects.