Mitigation of diabetes type II-induced nephropathy by ellagic acid nanoformulations: Amended glycemic control, oxidative stress, inflammation, and induced apoptosis

Diabetic nephropathy is a significant medical condition that arises from elevated blood sugar levels associated with both type I and type II diabetes. Recent research has indicated that ellagic acid (EA), either alone or in combination with other medications, can provide anti-diabetic benefits. This study aimed to explore the effects of EA and EA nanoformulations (EN) on nephropathy induced by type II diabetes in rats, while also investigating the underlying mechanisms at play. To induce type II diabetes, rats were fed a high-fat diet for four weeks, followed by a single intraperitoneal dose of streptozotocin (35 mg/kg), and continued on the high-fat diet for an additional four weeks. Diabetic rats were then treated with Metformin (M), EA, EN, EA + M, or EN + M for four weeks. The findings revealed that treatment with EN and the combination of M led to significant reductions in serum urea and creatinine levels, indicating an improvement in renal function. Additionally, EN and/or M effectively mitigated lipid peroxidation (LPO) levels in the affected kidneys, reduced fasting serum glucose, and lowered C-reactive protein (CRP) levels. Moreover, EN and/or M demonstrated the ability to prevent diabetes-induced histological alterations in the kidney glomeruli and tubules, as well as reduce collagen mesangial matrix formation. The presence of caspase 3, an apoptotic mediator, was significantly reduced in the kidneys of diabetic rats treated with EN and/or M. In conclusion, EN and/or M have the potential to prevent nephropathy induced by type II diabetes by enhancing glycemic control, reducing oxidative stress and inflammation, and scavenging free radicals, all of which contribute to apoptotic changes in kidney tissue.