BIOCHEMICAL AND PHARMACOLOGICAL PROPERTIES OF AFRICAN STAR APPLE (Chrysophyllum albidum Linn) LEAF EXTRACT IN GENTAMICIN-INDUCED HEPATO-RENAL DYSFUNCTIONS IN RATS

Abstract

Hepatic and renal dysfunctions are now major health challenges with attendant high mortality, morbidity and economic cost. Treatment with orthodox medicines have undesirable side effects necessitating the quest for alternative treatment options such as the use of medicinal plants which have shown high efficacy with fewer side effects in disease management. African star apple (Chysophyllum albidum Linn; family Sapotaceae) is used locally in Nigeria for the management of renal related ailments. This study evaluated the protective property of methanol leaf extract of African star apple (MCA) in gentamicin-induced hepato-renal dysfunctions in Wistar rats. Phytochemical screening, high performance liquid chromatography diode array detector (HPLC-DAD) fingerprinting and evaluation of in vitro antioxidant activity of MCA were carried out. Acute toxicity study was performed to establish the LD50 of the extract. Rats were administered varying doses of MCA for 14 days followed by biochemical and haematological evaluations to assess sub chronic toxicity. To evaluate the hepatoprotective and renoprotective properties of the extract, male Wistar rats were randomly distributed into normal control, positive control [gentamicin-toxified (80 mg/kg, i.p) group] and gentamicin-toxified animals co-administered with MCA (75, 150 or 300 mg/kg) and silymarin (100 mg/kg) silymarin serving as the reference group. After the treatments, urinalysis, assays for plasma biochemical parameters, tissue oxidative stress markers, pro-inflammatory markers and tissue damage/excitotoxicity were performed. Also, the mRNA expression of tumour necrosis factor alpha (TNF-α), interleukin-6, interleukin-1β, cystatin C, kidney injury molecule-1, neutrophil gelatinase actin lipocalin and paraxonase were evaluated. Flavonoids, saponins, tannins, alkaloids, phenolics, cardiac glycosides and steroids while stigmasterol (4.46±0.05 mg/g), epicatechin (1.13±0.02 mg/g), epigallocatechin (0.97±0.02 mg/g), β-amyrin acetate (2.82±0.04 mg/g), eleagine (0.76±0.01 mg/g) and gentisic acid (0.43±0.01 mg/g) were identified and quantified by HPLC-DAD. MCA showed appreciable in vitro antioxidant activity and was relatively safe to rats with an oral LD50 of >5000 mg/kg. Treatment of gentamicin-toxified animals with MCA resulted in significant (p<0.05) improvements in some altered biochemical parameters in both plasma and organs. Furthermore, a significant decrease was observed in pro-inflammatory activities in the kidney and liver after MCA treatment, renal myeloperoxidase activity in gentamicin-administered group was 32.67±2.88 mU/mg protein compared with 300 mg/kg treatment group which was 25.28±1.09 mU/mg protein. MCA treatment also down-regulated mRNA expression of TNF-α and kidney IL-6 and upregulated the expression of liver paraxonase. Groups treated with MCA and silymarin showed a significantly (p<0.05) lower level of expression of NGAL, KIM-1 and cystatin C when compared with the gentamicin-toxified group. The renal and hepatic histopathological findings further emphasized gentamicin-induced damage to the organs and the ameliorative effects of MCA. In conclusion, this study revealed the hepatoprotective and renoprotective properties of African star apple leaves and the probable mechanisms of action which include anti-redox stress effects, reduction of pro-inflammatory cytokines and modulation of liver paraxonase, NGAL, KIM-1 and Cystatin expressions.