Moringa oleifera leaves ethanolic extract influences DNA damage signaling pathways to protect liver tissue from cobalt -triggered apoptosis in rats

Abstract

This study assessed the potential of Moringa oleifera leaves ethanol extract (MLEE) in attenuating the detrimental effects of cobalt dichloride (CoCl₂) on rat liver. Forty rats were assigned to five equal groups: control group, MLEE-treated group, CoCl₂-treated group, prophylaxis co-treated group, and therapeutic co-treated group. The levels of Co, hepatic injury markers, total antioxidant capacity (TAC), and oxidative stress biomarkers (reactive oxygen species [ROS] and protein carbonyl [PC]) were evaluated. Comet assay was used to evaluate the extent of DNA damage. Further, the expression profile of DNA-damage effector genes was assayed by real-time quantitative polymerase chain reaction (qRT-PCR) analysis. Immunohistochemical analysis of heat shock protein (HSP-70) in hepatocytes was conducted. The results showed that the exposure of CoCl₂ to rats resulted in declined TAC, elevated oxidative injury, and induced DNA damage markers. Upregulation of mRNA expression of tumor suppressor protein (P53), apoptosis inducing factor (AIF), and apoptotic peptidase activating factor 1 (Apaf-1) was observed. The immunostaining density of HSP-70 expression was found to be elevated. Thus, MLEE reduced the CoCl₂-induced genotoxicity by preventing CoCl₂-induced generation of ROS, and protected against ROS mediated-oxidative injury and DNA damage. Moreover, the expression of DNA damage effector genes was affected. Based on these results, we conclude that MLEE is more effective when administered as a prophylactic regimen with the exposure to CoCl₂.

Keywords: AIF; Apaf-1; Cobalt; Comet assay; HSP-70; Moringa oleifera.