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

The ameliorative effect of Annona muricata in glycerol-induced acute kidney injury in laboratory rats was evaluated. Methods: Thirty 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, immuno- histochemistry, and changes in blood pressure were indices of toxicity. Results: In the toxicant group, blood pressure increased significantly (p < 0.05), but treat- ment 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 lev- els 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 kid- ney histology with no observable lesion. The immunolocalization of angiotensin-converting enzyme and kidney injury molecule-1 in the kidney showed high expression of these pro- teins in the toxicant group. At the same time, enalapril and the extract caused significant downregulation of their expressions.