PROTECTIVE EFFECT OF ONION EXTRACT AND QUERCETIN ON CAPECITABINE -INDUCED CYTOTOXICITY AND GENOTOXICITY IN GERM CELLS OF MICE

*Olajumoke Omolara Ojo, Adesua Oluwatumininu O. and Ajayi Oluwadamilare O.

ABSTRACT

Possible adverse effects of Capecitabine (CPB) treatment on reproductive functions and testicular DNA damage along with the potential protective effects of Quercetin and Onion extract on the germ cell toxicity were investigated. CPB was administered intraperitoneally (i.p.) at the dose of 5, 10 and 20mg/kg/bwt to male mice weighing 25g (n=5) daily for 21 days. Quercetin and Onion extract were given at the dose of 10mg/kg prior to CPB dosing each day. Body weight, testes and epididymis weights, testosterone and Luteinizing hormone levels (ELISA), sperm counts, motility, morphology and histology were evaluated. The DNA damage using halo assay and single-cell gel electrophoresis technique (COMET assay) was also measured. Reactive oxygen species (ROS) and Malondialdehyde (MDA) levels along with important antioxidant biomarker enzymes GSH, CAT and SOD were also evaluated. Raised ROS and MDA, the final product of fatty acid peroxidation levels with reduced testosterone and LH levels were measured. Depletion of antioxidant enzymes confirmed generation of oxidative stress following CPB treatment resulting to impaired functions of testicular tissue. DNA damage increased in a dose-dependent manner. However, quercetin and onion extract treatments significantly improved the testes weight, sperm count, motility and morphology as compared to only CPB- treated animals. Quercetin and onion extract co-treatment also significantly (p<0.05) restored the sperm DNA damage. Further, QUC and onion extract treatments showed protection against CPB-induced testicular toxicity as evident from testes histology. The present results confirmed damage of testicular tissue following CPB treatment. The studies also showed the ameliorative potential of quercetin from onion-extract against CPB -induced cytotoxicity and genotoxicity in male mice.

Keywords: Capecitabine; Quercetin; Onion; Oxidative stress; Halo assay; single cell gel electrophoresis assay.