Comparative Evaluation of Vehicle, Dose, and Duration-related Oxidative, Cardiotoxic, Inflammatory and Histologic Responses of Chromium 6+ and Doxorubicin in Rats’ Heart

Abstract

Doxorubicin (Dox) is cardiotoxicity is established while chromium 6+ compound (Cr[VI]) could be cardiotoxic due to its bioaccumulation capacity. This study compared vehicle, dose, and duration-related oxidative, cardiotoxic, inflammatory and histologic responses of Cr[VI] and Dox intoxication in rats’ heart by standard protocols. The rats were respectively intoxicated with Cr [VI] and Dox in 3 different phases. In the first phase, sixty rats were assigned to six groups of ten each. Group 1 served as the Control while groups 2, 3, and 4 were treated with oral doses of 10, 20, and 30 mg/kg body weight (b.wt) of K2Cr2O7 (Cr[VI]) solution while groups 5 and 6 received intraperitoneal administration of 15 and 20 mg/kg b.wt Dox for two days, respectively, before the sacrifice. The procedure was repeated in the second and third Phases, but for 60 days. Oxidative, cardiotoxic, inflammatory and histologic indices were determined in the rats’ heart. The results indicated that exposure to either Dox or Cr{VI] caused a significant (P < 0.05) dose, vehicle and duration-dependent decrease in Superoxide dismutase (SOD), Glutathione peroxidase (GPx), Catalase (CAT) activities and Nitric Oxide(NO) levels but an increase in Cardiac Troponin (CTnI) levels, Creatinine-kinase (CK-MB), C-reactive protein(CRP), Aspartate-transaminase(AST), Lactate-dehydrogenase (LDH) and Malondialdehyde (MDA) compared to the control. Heart histopathology of Dox- and Cr[VI] treated rats showed dose, vehicle and duration-dependent pulmonary oedema, hyaline necrosis and displacement of adjacent myocytes compared to control. Thus, Cr[VI] compared well with Dox in cardiotoxicity induction accompanied with oxidative stress, inflammatory and histo-hepatic responses in the rats’ heart.