Garcinia kolaheckel stem bark ethanolic extract and its triterpenoid fraction protected against sodium arsenite-induced hepatotoxicity and nephrotoxicity in rat models

Thesis Abstract

Arsenite is an environmental toxicant known to elicit adverse effects on liver and kidney organs. This study was designed to investigate the protective effects of Garcinia kola Heckel stem bark ethanolic extract (EEGK) and triterpenoid fraction (TFGK) against sodium arsenite-induced hepatotoxicity and nephrotoxicity in rats.

Sodium arsenite was used to induce hepatotoxicity and nephrotoxicity in Wistar strain albino rats for 14 days.EEGK and TFGK were used as test samples while silymarin served as a standard drug for comparison. Biomarkers measured were plasma alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), urea, and creatinine. Ferric reducing antioxidant potential (FRAP), 1-1- diphenyl 2-picryl hydrazyl (DPPH), hydroxyl radical scavenging activity (HRSA), and total antioxidant capacity (TAC) assays were used to determine the antioxidant activity in vitro and In vivo antioxidant assays on the liver, kidney, and plasma superoxide dismutase (SOD), glutathione peroxidase (GPx) and reduced glutathione (GSH) were carried out. In vitro mitochondrial membrane permeability transition (MMPT) was carried out. Histopathological examination of liver and kidney sections were performed and GC-MS analytical method was used to identify the bioactive compounds present in TFGK and EEGK.

Data showed that TFGK reduced ALT, AST, ALP activity and total bilirubin while EEGK reduced plasma creatinine and urea. Furthermore, EEGK elevated DPPH and hydroxyl radical scavenging activity, FRAP, and TAC when compared with TFGKin vitro. In addition, EEGK elevated plasma, liver and kidney SOD, GPx, GSH while TFGK modulated hematological markers. Further study showed thatTFGK inhibited the formation of liver and kidney MMPT.Histopathological examination showed that TFGK and EEGK reversed sodium arsenite-induced hepatotoxicity and nephrotoxicity respectively. GC/MS analysis detected 14 bioactive compounds in EEGK and 15 bioactive compounds in TFGK.

The study concluded that TFGK substantially protected against sodium arsenite-induced hepatotoxicity than EEGK while EEGK substantially protected against sodium arsenite-induced nephrotoxicity than TFGK. In addition, this study provided scientific insight to account for the traditional use of G. kola stem bark extract in ethnomedical practice.

Keywords Stem bark; antioxidant; protection; toxicity; liver; kidney; mitochondrial; histopathology