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

2021 ◽  
Vol 17 (1) ◽  
Author(s):  
Kanchana Kengkoom ◽  
Wannee Angkhasirisap ◽  
Tapanee Kanjanapruthipong ◽  
Rongdej Tungtrakanpoung ◽  
Khwanchanok Tuentam ◽  
...  
Keyword(s):  
Kidney Disease ◽  
Diabetic Kidney Disease ◽  
Disease Model ◽  
Wistar Rat ◽  
Male Rats ◽  
Tubular Damage ◽  
Diabetic Kidney ◽  
Filtration Apparatus ◽  
Clinical Illness ◽  
Renal Tubular

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. 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. 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.

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

2021 ◽  
Author(s):  
Kanchana Kengkoom ◽  
Wannee Angkhasirisap ◽  
Tapanee Kanjanapruthipong ◽  
Rongdej Tungtrakanpoung ◽  
Khwanchanok Tuentam ◽  
...  
Keyword(s):  
Kidney Disease ◽  
Diabetic Kidney Disease ◽  
Disease Model ◽  
Wistar Rat ◽  
Immunogold Labelling ◽  
Male Rats ◽  
Tubular Damage ◽  
Diabetic Kidney ◽  
Clinical Illness ◽  
Renal Tubular

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.

scholarly journals Streptozotocin induces alpha-2u globulin nephropathy in male rats during the end-stage of diabetic kidney disease

2020 ◽  
Author(s):  
Kanchana Kengkoom ◽  
Wannee Angkhasirisap ◽  
Tapanee Kanjanapruthipong ◽  
Rongdej Tungtrakanpoung ◽  
Khwanchanok Tuentam ◽  
...  
Keyword(s):  
Kidney Disease ◽  
Diabetic Kidney Disease ◽  
Disease Model ◽  
Wistar Rat ◽  
Immunogold Labelling ◽  
Male Rats ◽  
Tubular Damage ◽  
Diabetic Kidney ◽  
Renal Tubular ◽  
End Stage

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 prove 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 end-stage kidney disease. 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 end-stage diabetic kidney disease 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 end-stage diabetic kidney disease in association with deterioration of renal filtration, renal tubular damage with adaptation and mitochondrial apoptosis.

Ectopic lipid accumulation: potential role in tubular injury and inflammation in diabetic kidney disease

2018 ◽  
Vol 132 (22) ◽  
pp. 2407-2422 ◽  
Author(s):  
Wenxia Yang ◽  
Ying Luo ◽  
Shikun Yang ◽  
Mengru Zeng ◽  
Shumin Zhang ◽  
...  
Keyword(s):  
Kidney Disease ◽  
Lipid Accumulation ◽  
Diabetic Kidney Disease ◽  
Mononuclear Cells ◽  
Regulatory Element ◽  
Tubular Damage ◽  
Tubular Injury ◽  
Diabetic Kidney ◽  
Tnf Α ◽  
Significant Difference

Emerging studies suggest that lipid accumulates in the kidneys during diabetic kidney disease (DKD). However, the correlation between ectopic lipid accumulation with tubular damage has not been thoroughly elucidated to date. Using Oil Red staining, lipid accumulation was observed in the kidneys of type 2 DKD patients (classes II–III) and db/db mice compared with the control and was predominantly located in the proximal tubular compartment. Immunohistochemistry (IHC) staining showed that the intensity of adipose differentiation related protein (ADRP) and sterol regulatory element binding protein-1 (SREBP-1) was clearly up-regulated, which was positively correlated with the tubulointerstitial damage score and inflammation. Furthermore, the urine ADRP content significantly increased in DKD patients compared with the control, which positively correlated with abnormal lipid metabolism, serum creatinine, urine N-acetyl-β-glucosaminidase (NAG), albumin excretion (albumin-to-creatinine ratio (ACR)), and tumor necrosis factor-α (TNF-α) expression. However, there was no significant difference observed in plasma ADRP levels. In addition, the expression of SREBP-1 protein was dramatically increased in peripheral blood mononuclear cells (PBMCs) isolated from DKD patients, which was also tightly correlated with urine NAG, ACR, and TNF-α levels. In vitro studies demonstrated increased ADRP and SREBP-1 expression accompanied by lipid accumulation in HK-2 cells cultured in high glucose (HG). HG induced high levels of TNF-α expression, which was partially blocked by transfection of ADRP siRNA or SREBP-1 siRNA. These data indicated that ADRP and SREBP-1 are crucial factors that mediate lipid accumulation with tubular damage and inflammation in DKD, and ectopic lipid accumulation may serve as a novel therapeutic target for amelioration of tubular injury in DKD.

scholarly journals 20(S)-Ginsenoside Rg3 Protects Kidney from Diabetic Kidney Disease via Renal Inflammation Depression in Diabetic Rats

2020 ◽  
Vol 2020 ◽  
pp. 1-8
Author(s):  
Tong Zhou ◽  
Lin Sun ◽  
Shuo Yang ◽  
You Lv ◽  
Yue Cao ◽  
...  
Keyword(s):  
Treatment Group ◽  
Kidney Disease ◽  
Cell Apoptosis ◽  
Diabetic Kidney Disease ◽  
Diabetic Rats ◽  
Diabetic Group ◽  
Renal Tubular Cell ◽  
Ginsenoside Rg3 ◽  
Diabetic Kidney ◽  
Renal Tubular

20(S)-Ginsenoside Rg3 (20(S)-Rg3) has been shown to induce apoptosis by interfering with several signaling pathways. Furthermore, it has been reported to have anticancer and antidiabetic effects. In order to detect the protective effect of 20(S)-Rg3 on diabetic kidney disease (DKD), diabetic rat models which were established by administering high-sugar, high-fat diet combined with intraperitoneal injection of streptozotocin (STZ), and age-matched wild-type (WT) rat were given 20(S)-Rg3 for 12 weeks, with three groups: control group (normal adult rats with saline), diabetic group (diabetic rats with saline), and 20(S)-Rg3 treatment group (diabetic rats with 20(S)-Rg3 (10 mg/kg body weight/day)). The biochemical indicators and the changes in glomerular basement membrane and mesangial matrix were detected. TUNEL staining was used to detect glomerular and renal tubular cell apoptosis. Immunohistochemical staining was used to detect the expression of fibrosis factors and inflammation factors in rat kidney tissues. Through periodic acid-Schiff staining, we observed that the change in renal histology was improved and renal tubular epithelial cell apoptosis decreased significantly by treatment with 20(S)-Rg3. Plus, the urine protein decreased in the rats with the 20(S)-Rg3 treatment. Fasting blood glucose, creatinine, total cholesterol, and triglyceride levels in the 20(S)-Rg3 treatment group were all lower than those in the diabetic group. Mechanistically, 20(S)-Rg3 dramatically downregulated the expression of TGF-β1, NF-κB65, and TNF-α in the kidney. These resulted in a significant prevention of renal damage from the inflammation. The results of the current study suggest that 20(S)-Rg3 could potentially be used as a novel treatment against DKD.

scholarly journals Effects of Pentoxifylline on Soluble Klotho Concentrations and Renal Tubular Cell Expression in Diabetic Kidney Disease

Diabetes Care ◽  
2018 ◽  
Vol 41 (8) ◽  
pp. 1817-1820 ◽  
Author(s):  
Juan F. Navarro-González ◽  
María Dolores Sánchez-Niño ◽  
Javier Donate-Correa ◽  
Ernesto Martín-Núñez ◽  
Carla Ferri ◽  
...  
Keyword(s):  
Kidney Disease ◽  
Diabetic Kidney Disease ◽  
Tubular Cell ◽  
Renal Tubular Cell ◽  
Diabetic Kidney ◽  
Renal Tubular ◽  
Cell Expression

scholarly journals Exercise Ameliorates Diabetic Kidney Disease in Type 2 Diabetic Fatty Rats

Antioxidants ◽  
2021 ◽  
Vol 10 (11) ◽  
pp. 1754
Author(s):  
Itaru Monno ◽  
Yoshio Ogura ◽  
Jing Xu ◽  
Daisuke Koya ◽  
Munehiro Kitada
Keyword(s):  
Kidney Disease ◽  
Diabetic Kidney Disease ◽  
Molecular Mechanisms ◽  
Kidney Injury ◽  
Male Rats ◽  
Fatty Acid Binding ◽  
Diabetic Kidney ◽  
Beneficial Effects ◽  
Type 2 Diabetic

Lifestyle improvement, including through exercise, has been recognized as an important mode of therapy for the suppression of diabetic kidney disease (DKD). However, the detailed molecular mechanisms by which exercise exerts beneficial effects in the suppression of DKD have not yet been fully elucidated. In this study, we investigate the effects of treadmill exercise training (TET) for 8 weeks (13 m/min, 30 min/day, 5 days/week) on kidney injuries of type 2 diabetic male rats with obesity (Wistar fatty (fa/fa) rats: WFRs) at 36 weeks of age. TET significantly suppressed the levels of albuminuria and urinary liver-type fatty-acid-binding protein (L-FABP), tubulointerstitial fibrosis, inflammation, and oxidative stress in the kidneys of WFRs. In addition, TET mitigated excessive apoptosis and restored autophagy in the renal cortex, as well as suppressed the development of morphological abnormalities in the mitochondria of proximal tubular cells, which were also accompanied by the restoration of AMP-activated kinase (AMPK) activity and suppression of the mechanistic target of rapamycin complex 1 (mTORC1). In conclusion, TET ameliorates diabetes-induced kidney injury in type 2 diabetic fatty rats.

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