Cisplatin (CS) is a widely used chemotherapeutic agent, but its side effects, such as neurotoxicity, limit its clinical application. The present study investigated the protective role of betaine, a methyl donor with antioxidant and anti-inflammatory properties, against CS induced neurotoxicity mediated by oxidative stress using immunohistochemical methods. Forty female Wistar albino rats (8-10 weeks old, 200-250g) were randomly divided into four groups: Control, Betaine, CS, and CS+Betaine. Betaine (250mg/kg) was administered orally, while CS (8mg/kg) was administered intraperitoneally once a week for four weeks. Histopathological and immunohistochemical analyses were performed on the cerebral cortex/medulla and hippocampal tissues using HIF-1α, VEGF, EPO, GFAP, and caspase-3 markers. Statistical analyses were performed using GraphPad Prism 10. Histopathological examination revealed that CS administration caused hypereosinophilic degeneration in pyramidal neurons, which was alleviated in the CS+Betaine group. Immunohistochemical analysis showed that CS significantly increased the expression of HIF-1α, VEGF, EPO, and GFAP compared to the control group, while co-administration with betaine tended to reduce these increases; however, the reductions did not reach statistical significance. Caspase-3 expression was also high in the CS group, indicating increased apoptosis, while betaine attenuated this effect. Betaine may exert neuroprotective effects through its antioxidant and anti-apoptotic potential. These findings suggest that betaine may have therapeutic potential in reducing CS-associated neurotoxicity.

To Cite This Article: Ülger M and Bayram LC 2025. Neuroprotective potential of betaine in cisplatin-treated rats: a histopathological and immunohistochemical analysis. Pak Vet J. http://dx.doi.org/10.29261/pakvetj/2025.202