scholarly journals Amelioration of Diabetic Nephropathy by Targeting Autophagy via Rapamycin or Fasting: Relation to Cell Apoptosis/Survival

2021 ◽  
Vol 43 (3) ◽  
pp. 1698-1714
Author(s):  
Khaled Gouda ◽  
Sherihan AbdelHamid ◽  
Ahmed Mansour ◽  
Nesreen Omar ◽  
Hala El-Mesallamy

Autophagy has been demonstrated to have a beneficial effect on diabetic nephropathy (DN). Rapamycin, an inhibitor of mTOR, was shown to stimulate β-cell autophagy. However, its effects on preventing or ameliorating DN is unclear, and its effects are worth studying. As fasting is now an attractive protective strategy, we aim to compare its effect to rapamycin effects on pancreatic and renal cells. Twenty-eight adult male Wistar Albino rats were randomly divided into four groups, using streptozotocin (STZ) to induce diabetes mellitus (DM). Autophagy was induced by two ways; rapamycin or fasting. The extent of autophagy and apoptosis were investigated by measuring the level of LC3B and p53 proteins, respectively, in pancreatic and kidney tissues using Western blotting (WB) technique and imaging the renal cells under transmission electron microscope. The efflux transporter P-glycoprotein was quantified by WB as well. Rapamycin-induced autophagy occurred concurrently with apoptosis. On the other hand, fasting supported P-glycoprotein recovery and renal cell survival together with disabling β-cells apoptosis. In conclusion, this study provides a potential link between rapamycin or fasting for the cross-regulation of apoptosis and autophagy in the setting of cell stress as DN. Unlike rapamycin, fasting enhanced the active expression of ABCB1 efflux protein, providing insights on the potential ameliorative effects of fasting in DN that require further elucidation.

Author(s):  
Amin Al-Doaiss ◽  
Yazun Jarrar ◽  
Ali Shati ◽  
Mohammad Alfaifi ◽  
Mohammed Al-Kahtani ◽  
...  

Background: Atorvastatin (ATOR) is widely used for the treatment and prevention of hypercholesterolemia and various diseases, such as cardiovascular complication, with little data about the histopathological and ultrastructural renal alterations that might be induced by this drug. Objectives: The present study was undertaken to investigate the potential toxicity of therapeutic doses of atorvastatin on the microanatomy and ultrastructure of renal tissues from Wistar albino rats. Methods: Adult male Wistar albino rats received an oral daily dose of 5 mg/kg body weight for 90 consecutive days. Biopsies from both kidneys of each study rat were taken for histopathological and ultrastructural examination. Results: ATOR-treated rats exhibited glomerular, tubular, and interstitial histological alterations, including degeneration, necrosis, hyaline droplets, edema, cortical hemorrhages, mesangial hypercellularity, and blood capillary dilation and congestion. In addition, ATOR exposure increased the activity of glucose-6-phosphate dehydrogenase and alkaline phosphatase with a concurrent reduction in proteins and neutral mucosubstances content of the glomeruli and renal cells. Moreover, ATOR-treated animals demonstrated glomerular ultrastructural alterations, consisting mainly of capillary tuft dilatation, glomerular basement membrane thickening, and mesangial cell proliferation. The renal cells of the proximal tubules demonstrated damaged mitochondria, degenerative cellular changes, endoplasmic reticulum dilatation, lysosomal and autophagosome activation, nuclear alteration, myelin figure formation, and microvilli disorganization. Conclusion: The findings of the present work may indicate that ATOR can induce renal histological, histochemical, and ultrastructural alterations that may affect kidney and other vital organ function.


2016 ◽  
Vol 19 (6) ◽  
pp. 464-470 ◽  
Author(s):  
Amel Mahmoud Soliman ◽  
Ayman Saber Mohamed ◽  
Mohamed-Assem Said Marie

Background. The main complication of diabetes mellitus is diabetic nephropathy in both types, which is a main reason for renal failure. Echinochrome substance present in sea urchin shells and spines and possesses high antioxidant activity.Aim. is to evaluate the ability of Ech to suppress the progression of diabetic complication in kidney.Materials and methods. Thirty-six male Wistar albino rats were divided into two main groups, type 1 diabetes mellitus and type 2 diabetes mellitus. Both groups divided into control, diabetic and echinochrome subgroups. Type 1 diabetes was induced by single dose of streptozotocin (60 mg/kg, i.p), while type 2 was induced by high fat diet for 4 weeks before the injection with streptozotocin (30 mg/kg, i.p). The treated groups were administrated by echinochrome (1mg/kg body weight in 10% DMSO) daily for 4 weeks.Results. Echinochrome groups showed reduction in the concentrations of glucose, malondialdehyde, urea, uric acid and creatinine. While it caused general increase in glutathione-S-transferase, superoxide dismutase, catalase, glutathione reduced, nitric oxide and creatinine clearance. The histopathological investigation showed clear improvement in the kidney architecture.Conclusion. Administration of echinochrome improves renal function and ameliorates renal histopathological changes possibly by improvement of glucose metabolism and inhibition of lipid peroxidation process.


2021 ◽  
Vol 16 (3) ◽  
pp. 091-102
Author(s):  
Esraa Abu El Qassem Mahmoud ◽  
Ayman S Mohamed ◽  
Sohair R Fahmy ◽  
Amel Mahmoud Soliman ◽  
Khadiga Gaafar

Aims: The present study aimed to evaluate anti-diabetic properties of AgNPs/chitosan/ascorbic acid nanocomposites (Ag-NCs) in streptozotocin-induced diabetic rats. Main methods: Eighteen male Wistar albino rats were divided into three main groups (6 rats/group); control, diabetic and Ag-NCs groups. Control group: after a single dose of citrate buffer (0.1 mol/l, i.p), the rats orally received 1 ml distilled water daily for four weeks. The diabetic model was induced by a single dose of streptozotocin (60 mg/kg, i.p) for type 1diabetes. Diabetic groups were treated orally with and Ag-NCs (0.25mg/Kg body weight) daily for four weeks. Key findings: AgNPs/chitosan/ascorbic acid nanocomposite group showed a reduction in the concentrations of glucose, NO, MDA, creatinine, urea and uric acid. At the same time, it appeared a general increase in insulin, CAT, and SOD activities and GSH concentration. The histopathological investigation illustrated a clear improvement in renal architecture. Significance: The suggested mechanism of action for Ag-NCs in decreasing diabetic nephropathy includes two pathways; the hypoglycemic activity and the antioxidant role of Ag-NCs


Author(s):  
Pradeep Deshmukh ◽  
Tanaji Nandgude ◽  
Mahendra Singh Rathode ◽  
Anil Midha ◽  
Nitin Jaiswal

The suspensions of alcoholic extract of root bark of the plant Calotropis gigantea in 0.6% carboxy methyl cellulose (CMC) were evaluated for hepatoprotective activity in Wistar albino rats by inducing hepatic injury with D-galactosamine (400 mg/kg). Alcoholic extract of root bark of the plant Calotropis gigantea at an oral dose of 200 mg/kg and 400 mg/kg exhibited a significant (P<0.001, P<0.01 and P<0.05) protection effect by normalizing the levels of aspartate amino transferase (ASAT/ GOT), alanine amino transferase (ALAT/GPT), alkaline phosphatase (ALP), total bilirubin (TB), lactate dehydrogenase (LDH), which were significantly (P<0.001) increased in rats by treatment with 400 mg/kg i.p. of D-galactosamine. Silymarin (25 mg/kg), a known hepatoprotective drug used for comparison exhibited significant activity (P<0.001).


2020 ◽  
Vol 19 (2) ◽  
pp. 217-221
Author(s):  
Maria Jesús Lisbona-González ◽  
Candela Reyes-Botella ◽  
Esther Muñoz-Soto ◽  
Maria Victoria Olmedo-Gaya, ◽  
Jorge Moreno-Fernandez ◽  
...  

Adipose tissue is an endocrine organ and has central role in interaction with other organs or tissues while propolis can induce lipolysis. Therefore, the aim of this study is to provide detailed information about adipose tissue homeostasis modifications and body composition during propolis supplement consumption. Twenty male Wistar albino rats (8 weeks) were divided into two groups of 10 animals each and fed for 90 days with two different types of diets: standard for the control group (diet C) and standard diet + 2% propolis (diet P). Thyroid hormones did not show differences, while ghrelin and adiponectin decreased in the group that was fed propolis. Insulin, leptin, and non-esterified fatty acids also increased along with reduced body weight and fat, in addition to increased lean mass when propolis was in the diet. We conclude that propolis could decrease ghrelin and adiponectin but increase non-esterified fatty acids and insulin secretion, which improves body composition.


2017 ◽  
Vol 24 (1) ◽  
pp. 22 ◽  
Author(s):  
S. Priyanga ◽  
S. Hemmalakshmi ◽  
B. Vidya ◽  
P. Chella Perumal ◽  
V. K. Gopalakrishnan ◽  
...  

Sign in / Sign up

Export Citation Format

Share Document