Annona senegalensis stem bark extracts attenuated doxorubicin-induced hepatotoxicity and mitochondrial oxidative damage in Wistar strain albino rats

Abstract

Background and Objective: Doxorubicin (DOX)- an anthracycline is a well-known anticancer agent but its limitation lies in it hepato- and cardio-toxicity involving the mitochondrial redox pathway. Thus, there is need for chemoprotective agents to serve as interventions for militating against toxicity during cancer management. This study investigated the protective potential of Annona senegalensis stem bark extracts (ASE) on DOX-induced mitochondrial membrane damage and oxidative stress in albino rats’ livers.

Materials and Methods: ASE was subjected to phytochemical screening. Thirty male Wistar strain albino rats (13 weeks old; 150–160g) were randomly divided into Groups A (control) received distilled water, Groups B, C, D, E, and F received DOX-only (20mg/kg), DOX (20mg/kg) + ASE (100mg/kg), DOX (20mg/kg) + ASE (200mg/kg), DOX (20mg/kg) + ASE (400mg/kg), ASE (400mg/kg) only, respectively (n = 5 per group). Groups that received ASE were pre-administered for 7 days before intraperitoneal administration of DOX on day 7. Rats were sacrificed, oxidative stress and liver membrane damage were evaluated.

Results: Tannin, saponin, phenol, flavonoids, alkaloids, terpenoids, reducing sugar, and cardiac glycosides were present, while combined and free anthraquinone were absent in ASE. The total flavonoid, phenol, tannin, and reducing sugar content of ASE were 13.11±1.09, 27.19±0.61, 8.98±1.2, and 27.3±1.6mg gallic acid equivalent, respectively. Activities of catalase, superoxide dismutase, and level of glutathione in both hepatic mitochondrial membrane and post-mitochondrial fractions (PMF) increased concentration-dependently in ASE pretreated compared to DOX-only-treated animals. Malondialdehyde levels significantly (P < 0.05) decreased concentration-dependently.

Conclusions: ASE has chemoprotective potential on liver mitochondria and PMF against DOX-induced toxicity attributable to its constituent phytochemicals.