Cholecalciferol Ameliorates Cyclophosphamide-induced Behavioural Toxicities in Wistar Rats

Dosunmu Damilare Paul¹, Onaolapo Adejoke Yetunde², Onaolapo Olakunle James^1,3

1. Department of Pharmacology and Therapeutics, Ladoke Akintola University of Technology, Ogbomoso, Oyo State, Nigeria. 
2. Behavioural Neuroscience and Neurobiology Unit, Department of Anatomy, Ladoke Akintola University of Technology, Ogbomoso, Oyo State, Nigeria, orcid.org/0000-0001-7126-7050 
3. Behavioural Neuroscience and Neuropharmacology Unit, Department of Pharmacology and Therapeutics, Ladoke Akintola University of Technology, Ogbomoso, Oyo State, Nigeria orcid.org/0000-0003-2142-6046

ABSTRACT 

Cholecalciferol (Vitamin D3) is a dietary supplement that has been shown to play crucial roles in brain development, immune regulation, neurotransmission and neuroprotection. While there are reports that it influences cognition and mental health there is a dearth of information on its benefits in mitigating cyclophosphamide induced behavioural deficits. This study investigated the possible protective effects of cholecalciferol supplementation on cyclophosphamide induced alterations in open field behaviours, spatial working memory and anxiety-related behaviours in rats. 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 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. At the end of the experimental period, animals were exposed to the behavioural paradigm (open field, Y-maze, and elevated plus maze). Vitamin D3 mitigated CYP-induced anxiogenic behaviour (dose-dependent). It also significantly improved spatial working memory. The results highlight Vitamin D3’s ability to influence CYP-induced loss in cognition in rats via its anxiolytic, cognitive and immune modulatory properties. They also harness Vitamin D3’s potential as a possible adjunct in cancer chemotherapy. However, further research will be needed to specify its exact role in cancer chemotherapy. 

KEYWORDS: Anxiety, Chemotherapy; Memory, Neurosteroid, Secosteroids, Vitamin D3