THEOBROMA CACAO STEM BARK AMELIORATES DOXORUBICIN-INDUCED OXIDATIVE STRESS, TESTICULAR AND LUNGS DAMAGE IN EXPERIMENTAL RATS

Kosoko A. M.*, Olurinde O. J. and Akinloye O. A.

ABSTRACT

Doxorubicin (DOX), a chemotherapy drug, is used to treat different types of cancer but its clinical use has been limited by dose-dependent multi-organ toxicities especially to the lungs, testes, heart and liver. Eighty rats, randomly selected, were divided into three (3) treatment groups: pre-, co- and post-treatment groups; consisting of 6 sub-groups each (5 rats per sub-group); baseline, normal saline (2ml), α- lipoic acid (20mg/kg body weight), and 200mg/kg, 400mg/kg or 800mg/kg body weight Theobroma cacao stem bark aqueous extract (TCAE) sub-groups. All animals except those in baseline sub-group were intoxicated with 20mg/kg body weight DOX intraperitoneally. Animals in the pre-treatment group were administered a single dose of DOX followed by 7 days oral administration of normal saline, α- lipoic acid or graded doses of TCAE; co-treatment group were co-administered 2.86 mg/kg body weight DOX with either normal saline, α- lipoic acid or TCAE orally for 7 days while post treatment group were administered normal saline, α- lipoic acid or TCAE orally for 7 days and on the 8th day, intoxicated with a single dose of DOX. Animals were sacrificed (pre- and post- treatment group were sacrificed on the 9th day while the co-treatment group sacrificed on the 8th day), blood samples collected by retro-orbital plexus, testes and lungs harvested for biochemical assays and histopathological investigations. Data were analyzed using SPSS 20.0 statistical tool, significance of difference calculated using one-way analysis of variance (ANOVA) and Duncan multiple range test. DOX intoxication caused a significant increase in testicular and lungs acid phosphatase, lactate dehydrogenase, γ-glutamyl transferase activities with a concomitant decrease in alkaline phosphatase activity. DOX intoxication also caused a significant increase in the concentrations of hydrogen peroxide, malondialdehyde and protein carbonyl; activities of myeloperoxidase, NADPH oxidase and xanthine oxidase while significantly reducing the concentrations of reduced glutathione, ascorbic acid and α-tocopherol; and activities of catalase, superoxide dismutase, glutathione-S-transferase and glutathione peroxidase. Treatment with TCAE significantly ameliorated markers of testicular and lungs damage and pro-oxidant markers while elevating the organs antioxidant status. TCAE possess a potential ameliorative property against DOX induced testicular and lungs damage and oxidative stress.

Keywords: Chemoprevention; Theobroma cacao; Doxorubicin; Testicular toxicity; Lungs toxicity; Oxidative stress.