Vitamin D3 Protects against Cyclophosphamide-induced Neurotoxicity Via Modulation of Inflammatory Cytokines and Oxidative Stress Parameters

Dosunmu Damilare Paul¹, Babatunde Oluwatobiloba Bashirat², Onaolapo Olakunle James^1,3

1. Department of Pharmacology and Therapeutics, Ladoke Akintola University of Technology, Ogbomoso, Oyo State, Nigeria.
2. Department of Anatomy, Ladoke Akintola University of Technology, Ogbomoso, Oyo, State, Nigeria
3. Behavioural Neuroscience and Neuropharmacology Unit, Department of Pharmacology and Therapeutics, Ladoke Akintola University of Technology, Ogbomoso, Oyo State, Nigeria

ABSTRACT

Vitamin D₃’s antioxidative properties make it potentially beneficial in many conditions where oxidative stress is implicated in the pathological processes. The study investigated the possible protective effects of Vitamin D₃ on weight loss, feed intake, brain oxidative status, markers of inflammation and cerebral cortex histomorphology in rats administered Cyclophosphamide (CYP). Sixty rats were randomly assigned into six groups (n=10). Groups A and D served as Normal and Cyclophosphamide control respectively and were fed standard rat chow, groups B and E received Vitamin D₃ (300 IU/kg), while those in groups C and F received Vitamin D₃ (600 IU/kg). Animals in group A-C received intraperitoneal normal saline on day1, while groups D-F got intraperitoneal Cyclophosphamide (100 mg/kg/day on day1). Standard diet and Vitamin D₃ supplementation were administered daily for 15 days. After the experimental period, animals were euthanised and blood was taken for the assessment of biochemical parameters. Cerebral cortex was also processed for histological study. Vitamin D₃ mitigated CYP-induced weight loss. It also improved total antioxidant capacity while reducing CYP-induced lipid peroxidation. Interleukin-10 increased, while the CYP-induced increase in TNF-α were mitigated following Vitamin D₃ supplementation. Again, protective efforts in cerebral cortex histomorphology were observed. The results showed Vitamin D₃’s ability to protect against CYP-induced neurotoxicity in rats via modulation of inflammatory and oxidative stress parameters. It also highlighted Vitamin D₃’s potential as a possible adjunct in cancer chemotherapy-induced tissue damage. However, further research will be needed to specify its exact role in cancer chemotherapy.

KEYWORDS: Secosteroids; Chemotherapy; Inflammation, Histomorphology; Neuroprotection; Oxidative stress