Attenuation of Doxorubicin-induced Oxidative Stress and Organ Damage in Experimental Rats by Theobroma cacao Stem Bark

Eighty rats, randomly selected, were divided into three (3) treatment groups: pre-, co- and post-treatment; consisting of 6 sub-groups each (5 rats per sub-group); baseline, normal saline (2 ml), α-lipoic acid (20 mg/kg body weight), and 200 mg/kg, 400 mg/kg, or 800 mg/kg body weight Theobroma cacao stem bark aqueous extract (TCAE). Animals in the pre-treatment group were intoxicated with a single dose (20 mg/kg) of doxorubicin (DOX) intraperitoneally followed by 7 days oral administration of normal saline, α-lipoic acid or TCAE; co-treatment group were co-administered 2.86 mg/kg body weight of 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 (20 mg/kg intraperitoneally). Animals were sacrificed (pre- and post-treatment groups on the ninth day while the co-treatment group on the 8th day), blood samples collected by retro-orbital plexus, kidneys and spleen samples harvested for biochemical and histopathological investigations. A significant elevation in plasma urea and creatinine concentrations with perturbation in plasma electrolyte (K+, Na+, Cl-, HCO3-) concentrations were observed resulting from DOX intoxication. DOX caused a significant increase in activities of splenic ACP, LDH, γ-GT and ALP activities. A significant increase in renal and splenic concentrations of H2O2 generated, MDA and PC; XO, MPX and NOX activities while the concentrations of GSH, AsA and α-TOC; and the activities of SOD, CAT, GST and GPX were significantly reduced following DOX intoxication. Treatment with TCAE significantly attenuated renal and splenic tissue damage and pro-oxidant markers precipitated by DOX intoxication while restoring normalcy to tissue antioxidant markers. Theobroma cacao stem bark aqueous extract presents a potential candidate in the prevention of renal and splenic injury and dysfunction related to doxorubicin intoxication.