Abstract
BackgroundAlpha-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. Alpha-2u globulin nephropathy, 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 examined in STZ-induced diabetic Wistar rat model.ResultsMore 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.ConclusionsSTZ-induced alpha-2u globulin nephropathy during diabetic kidney disease in association with deterioration of pedicels, renal tubular damage with adaptation and mitochondrial driven apoptosis.
Highlights
Alpha-2u globulin nephropathy mainly shows toxicological pathology only in male rats induced by certain chemicals and drugs, such as levamisole
Along these lines of thought, histopathology, immunohistochemistry, electron microscopy and immunogold labelling techniques were performed to demonstrate the presence of alpha-2u globulin nephropathy in STZ-induced diabetic rats in relation to the alteration of (i) water reabsorption and filtration function as characterised by aquaporins (AQP)1, − 2, − 4 and − 5, (ii) mitochondrial energetic maintenance protein using haloacid dehalogenase-like hydrolase domain-containing protein (HDHD)-3 and (iii) mitochondrial apoptotic marker by NADHubiquinone oxidoreductase 75 kDa subunit (NDUFS)
The results revealed immunolocalisation of AQP-1 and -2, − 4, and − 5 in the Proximal convoluted tubules (PCTs) and Colleting duct (CD), respectively (Fig. 4a–f)
Summary
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). Sun and colleague suggested that, in an STZ-induced diabetic rat, alpha-2u globulin and its modified form are dysregulated in renal mitochondria, leading to a reduction in β-oxidation of long chain fatty acids, decreased energy supply, increased fatty acid depositions and renal damage [8] Along these lines of thought, histopathology, immunohistochemistry, electron microscopy and immunogold labelling techniques were performed to demonstrate the presence of alpha-2u globulin nephropathy in STZ-induced diabetic rats in relation to the alteration of (i) water reabsorption and filtration function as characterised by aquaporins (AQP)1, − 2, − 4 and − 5, (ii) mitochondrial energetic maintenance protein using haloacid dehalogenase-like hydrolase domain-containing protein (HDHD)-3 and (iii) mitochondrial apoptotic marker by NADHubiquinone oxidoreductase 75 kDa subunit (NDUFS)-
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