ABSTRACT
Diabetic renal injury is a microvascular complication associated with inflammation and oxidative stress, culminating in renal dysfunction. Conventionally, it is treated with hypoglycemic agents to address metabolic perturbations. However, the way to mitigate immunological, inflammation, and oxidative stress have seldom been studied. Hence, in the present study, the nephroprotective role of immunosuppressive and anti-inflammatory drugs, mycophenolate mofetil (MMF) in combination with the oral hypoglycemic agent glibenclamide, on streptozotocin (STZ)- induced diabetic renal damage was studied. Bodyweight, fasting blood glucose, and glycosylated hemoglobin levels were altered in the diabetic rats. Furthermore, renal injury was indicated by abnormal levels of urinary protein and creatinine and serum markers of renal function in diabetic rats. Hyperglycemia-induced oxidative stress and inflammation were also observed in the diabetic rats. The combination of MMF and glibenclamide treatment significantly attenuated the abnormal effects of hyperglycemia, oxidative stress, and inflammation-induced renal injury in diabetic rats. Histopathological studies confirmed the nephroprotective role of MMF and glibenclamide by reversing renal injury in diabetic rats. The present study suggests that MMF and glibenclamide have a protective role in STZ-induced diabetic renal damage.
Subject(s)
Blood Glucose , Diabetes Mellitus, Experimental , Diabetic Nephropathies , Glyburide , Hypoglycemic Agents , Kidney , Mycophenolic Acid , Oxidative Stress , Rats, Wistar , Animals , Glyburide/pharmacology , Glyburide/therapeutic use , Diabetes Mellitus, Experimental/complications , Diabetes Mellitus, Experimental/drug therapy , Mycophenolic Acid/pharmacology , Oxidative Stress/drug effects , Male , Diabetic Nephropathies/prevention & control , Diabetic Nephropathies/drug therapy , Kidney/drug effects , Kidney/pathology , Hypoglycemic Agents/pharmacology , Hypoglycemic Agents/therapeutic use , Blood Glucose/metabolism , Blood Glucose/drug effects , Immunosuppressive Agents/pharmacology , Streptozocin , Drug Therapy, Combination , Rats , Biomarkers/blood , Anti-Inflammatory Agents/pharmacology , Anti-Inflammatory Agents/therapeutic useABSTRACT
Chronic kidney disease (CKD) which is characterized by progressive loss of renal function and renal fibrosis is a worldwide public health problem. Hepatocyte growth factor (HGF) is a polypeptide that exhibits multiple functions including antifibrotic effects on kidneys. The present study was aimed at evaluating HGF levels and studying its association with markers of inflammation and oxidative stress in patients of predialysis and dialysis CKD. A total of 80 subjects including 20 healthy controls, 40 patients of CKD stage 1 to stage 5 (predialysis), and 20 CKD patients with end-stage renal disease on hemodialysis were recruited. HGF, high-sensitivity C-reactive protein (hsCRP), malondialdehyde (MDA), and ferric reducing ability of plasma (FRAP) were measured in all the subjects. HGF levels were significantly higher in all patients with CKD compared to controls. The levels were found to be lower in patients on dialysis than in the predialysis group; however, the difference was not statistically significant. hsCRP, MDA, and FRAP were significantly higher in all patients with CKD than in controls. HGF levels did not show a significant correlation with the markers studied. HGF levels were increased in response to renal injury in CKD patients. The levels were higher in predialysis patients of CKD than in CKD patients on dialysis. HGF levels may be used as an indicator of renal fibrosis in patients with CKD.
