Streptozotocin induces alpha-2u globulin nephropathy in male rats during diabetic kidney disease

Abstract

Background: Alpha-2u globulin nephropathy mainly shows toxicological pathology only in male rats induced by certain chemicals and drugs, such as levamisole (antiparasitic and anticancer drugs). Streptozotocin (STZ) is also an anticancer-antibiotic agent that has been used for decades to induce a diabetic kidney disease model in rodents. The purpose of this study is to determine if STZ causes alpha-2u globulin nephropathy in male rats during an advanced stage of diabetic kidney disease.Methods: To test this hypothesis, the present study used a male diabetic Wistar rat model with 45 mg/kg of STZ injected intraperitoneally. Hyperglycaemic rats were divided into 2 groups: with and without alpha-2u globulin deposition in proximal tubule. Alpha-2u globulin nephropathy was examined by histopathological and electron microscope studies. Water absorption and filtration capacities (via aquaporin [AQP]-1, -2, -4 and -5) and mitochondrial function (through haloacid dehalogenase-like hydrolase domain-containing protein [HDHD]-3 and NADH-ubiquinone oxidoreductase 75 kDa subunit [NDUFS]-1 proteins) were determined using immunohistochemistry, immunofluorescence and immunogold labelling techniques.Results: More than 80% of severe clinical illness rats induced by STZ injection simultaneously exhibited alpha-2u globulin nephropathy with mitochondrial degeneration and filtration apparatus especially pedicels impairment. They also showed significantly upregulated AQP-1, -2, -4 and -5, HDHD-3 and NDUFS-1 compared with those of the rats without alpha-2u globulin nephropathy.Conclusions: STZ-induced alpha-2u globulin nephropathy during diabetic kidney disease in association with deterioration of pedicels, renal tubular damage with adaptation and mitochondrial driven apoptosis.