Annona muricata mitigates glycerol-induced nephrotoxicities in male albino rats through signaling pathways of angiotensin conversion enzyme, kidney injury molecule-1, and antioxidant properties

Abstract

ObjectiveThe ameliorative effect of Annona muricata in glycerol-induced acute kidney injury in laboratory rats was evaluated. MethodsThirty albino rats were used and were divided into five of six rats per group. The first (control) group was given distilled water (2 ml/kg) for seven days, while the second (toxicant or glycerol alone) group was given only glycerol (10 ml/kg) on day 8. The third, fourth, and fifth groups received methanol leaf extract of Annona muricata (100 mg/kg), 200 mg/kg dose of the extract, and enalapril (10 mg/kg) respectively for seven days, and on day eight all received glycerol (10 ml/kg). Serum chemistry, histopathology, immunohistochemistry, and changes in blood pressure were indices of toxicity. ResultsIn the toxicant group, blood pressure increased significantly (p<0.05), but treatment with 200 mg/kg of the leaf extract reversed this. In biochemical analysis, the toxicant group had a significant increase in the levels of oxidative stress markers and decreased levels of some enzymatic and non-enzymatic antioxidants. Treatment with 200 mg/kg of the extract and enalapril reversed the trend. Histopathological changes were seen in the kidney of the toxicant group, but those treated with 200 mg/kg of the extract showed normal kidney histology with no observable lesion. The immunolocalization of angiotensin-converting enzyme and kidney injury molecule-1 in the kidney showed high expression of these proteins in the toxicant group. At the same time, enalapril and the extract caused significant downregulation of their expressions. ConclusionResults showed that 200 mg/kg dose extract of Annona muricata could confer effective protection on the kidney due to its anti-inflammatory, anti-hypertensive and antioxidant properties.