Alterations in kidney tissue following zinc supplementation to STZ-induced diabetic rats

Objective: This research was designed to probe into the effects of Dapagliflozin on renal interstitial fibrosis in diabetic rats through Smad3, TIMP1 and MMP24 pathway. Methods: Rats were bought to establish models, and then intervened by Dapagliflozin. Human mesangial cell lines (HMCs) stimulated by high glucose were purchased, and the Smad3, TIMP1 and MMP24 levels in rats after modeling and Dapagliflozin intervention were detected. The Smad3, TIMP1 and MMP24 protein expression in kidney tissue was examined after the rats were killed, and the expression in an intervention group (IG) and a blank group (BG) were analyzed. The cells were divided into three groups: Dapagliflozin intervention (Group 1), TGF-P1/Smad3 pathway inhibitor SIS3 intervention (Group 2) and no intervention (Group 3). The TIMP1 and MMP24 levels were assessed. Results: The Smad3 and MMP24 levels in group A were higher than those in other two groups (p < 0.05), while those of TIMP1 were lower (p < 0.05). Compared with pre-intervention, the Smad3 and MMP24 levels in groups A and B decreased (p < 0.05), while those of TIMP1 increased (p < 0.05). The Smad3 and MMP24 protein levels in groups A and B were higher than those in other two groups (p < 0.05), while those of TIMP1 was lower (p < 0.05). Compared with the BG, the Smad3 and MMP24 expression in the IG was lower (p < 0.05) and that of TIMP1 was higher (p < 0.05). The TIMP1 expression in Group 3 was lower (p < 0.05) and that of MMP24 was higher than those in Groups 1 and 2 (p < 0.05). Conclusion: Dapagliflozin can treat diabetic renal interstitial fibrosis by inhibiting TGF-P1/Smad3 signaling pathway, decreasing MMP24 and increasing TIMP1.

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Protective effect of hydro-alcoholic extract of achillea millefolium on renal injury and biochemical factors in streptozotocin-induced diabetic rats

Nutrition & Food Science ◽

10.1108/nfs-11-2020-0437 ◽

2021 ◽

Vol ahead-of-print (ahead-of-print) ◽

Author(s):

Arash Karimi ◽

Hamid Reza Niazkar ◽

Pouria Sefidmooye Azar ◽

Helda Tutunchi ◽

Mozhde Karimi ◽

...

Keyword(s):

Mrna Level ◽

Kidney Tissue ◽

Diabetic Control ◽

Diabetic Rats ◽

Achillea Millefolium ◽

Control Group ◽

Alcoholic Extract ◽

Content Type ◽

Management Of Complications ◽

Male Wistar Rats

Purpose Herbal medicine has been used for the management of complications of diabetes. The purpose of this paper is to examine the anti-diabetic effects of Achillea millefolium extract on diabetic rats. Design/methodology/approach To this aim, 32 male Wistar rats were randomly assigned into four groups in which each group comprised eight rats. The four experimental groups were as follows: control group, diabetic control (DC) group (STZ; 50 mg/kg), diabetic rats, receiving 250 mg/kg hydro-alcoholic extract of the A. millefolium (DAM) and diabetic rats, receiving 5 mg/kg glibenclamide (DG). After 21 days of the treatment course, tissues of the kidney and blood samples were collected for histopathological, biochemical and molecular analysis. Findings The concentration of malondialdehyde (MDA) and glucose serum were markedly reduced in the DC group while significantly increased in DG and DAM groups (1.11 ± 0.57 to 19.4 ± 3.5 and 17.8 ± 1.2 p = 0.002 and 325 ± 0.18 to 223 ± 0.11 and 211 ± 0.32 p = 0.02, respectively). Also, the activities of glutathione peroxidase (GPx) and superoxide dismutase (SOD) were markedly reduced in the DC group while significantly increased in DAM and DG groups (9.1 ± 2.21 to 18.7 ± 3.81 and 14.9 ± 3.1 p = 0.03 and p = 0.02, respectively). The concentrations of creatinine, blood urea nitrogen (BUN) and urea were substantially decreased in DAM and DG groups as compared with the DC group (0.49 ± 0.02 to 0.27 ± 0.01 and 0.25 ± 0.01 p = 0.01, 15.6 ± 2.1 to 7.2 ± 0.68 and 8.6 ± 1.2 p = 0.02 and 114 ± 9.4 to 59.8 ± 5.2 and 64 ± 5.2 p = 0.03, respectively). Also, Bcl-2-associated X protein (BAX) expression was significantly decreased in DAM and DG groups as compared with the DC group (1.3 ± 0.32 to 0.91 ± 0.03 and 0.93 ± 0.02 p = <0.01) and Bcl-2 expression were significantly increased in DAM and DG groups as compared with the DC group (0.42 ± 0.05 to 0.88 ± 0.07 and 0.85 ± 0.06 p = 0.01). Originality/value Diabetes led to degenerative damages in the kidney of rats and increased the mRNA level of Bax, while treatment with A. millefolium could protect the kidney tissue against diabetes complications and increased the mRNA expression of Bcl-2. This study indicated that A. millefolium extracts not only improves renal function as a result of anti-oxidant activity but also modulates some biochemical factors in diabetic rats.

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Anti-Diabetic Effects of the Ethyl-Acetate Fraction of Trichilia catigua in Streptozo-tocin-Induced Type 1 Diabetic Rats

Cellular Physiology and Biochemistry ◽

10.1159/000478761 ◽

2017 ◽

Vol 42 (3) ◽

pp. 1087-1097 ◽

Cited By ~ 10

Author(s):

Rodrigo Mello Gomes ◽

Luis Fernando de Paulo ◽

Cynthia Priscilla do Nascimento Bonato Panizzon ◽

Camila Quaglio Neves ◽

Bruna Colombo Cordeiro ◽

...

Keyword(s):

Ethyl Acetate ◽

Kidney Tissue ◽

Ethyl Acetate Fraction ◽

Diabetic Rats ◽

Diabetic Group ◽

Male Wistar Rats ◽

Food And Water Intake ◽

Pancreas Morphology ◽

Group D

Background/Aims: Trichilia catigua A. Juss., known as “catuaba” in Brazil, has been popularly used as a tonic for fatigue, impotence and memory deficits. Previously, our group demonstrated that the ethyl-acetate fraction (EAF) of T. catigua has antioxidant and anti-inflammatory effects. The present study evaluated the anti-diabetic activity of EAF in type 1 diabetic rats. Methods: Male Wistar rats were divided into four groups (N: non-diabetic group, D: type 1 diabetic group, NC: non-diabetic + EAF group and DC: type 1 diabetic + EAF group). The latter two groups were treated with 200 mg/kg EAF. Type 1 diabetes was induced by intravenous streptozotocin (STZ) injection (35 mg/kg). Starting two days after STZ injection, EAF was administered daily by gavage for 8 weeks. Results: EAF attenuated body mass loss and reduced food and water intake. EAF improved hyperglycaemia and other biochemical parameters, such as alkaline phosphatase (ALP), alanine aminotransferase (ALT) and aspartate aminotransferase (AST). Furthermore, the number of pancreatic β-cells and the size of the islets had increased by β-cell proliferation in the DC group. EAF promoted reduction in kidney tissue damage in STZ-induced diabetic rats by reduction of renal fibrosis. Conclusion: The present study showed that EAF improves glucose homeostasis and endocrine pancreas morphology and inhibits the development of diabetic nephropathy in STZ-induced diabetic rats.

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The effects of chard (Beta vulgarisL. var. cicla) extract on the kidney tissue, serum urea and Creatinine levels of diabetic rats

Phytotherapy Research ◽

10.1002/ptr.1041 ◽

2002 ◽

Vol 16 (8) ◽

pp. 758-761 ◽

Cited By ~ 18

Author(s):

R. Yanardağ ◽

Ş. Bolkent ◽

Ö. Özsoy-Saçan ◽

Ö. Karabulut-Bulan

Keyword(s):

Kidney Tissue ◽

Diabetic Rats ◽

Serum Urea

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Protective effects of saffron (its active constituent, crocin) on nephropathy in streptozotocin-induced diabetic rats

Human & Experimental Toxicology ◽

10.1177/0960327114538989 ◽

2014 ◽

Vol 34 (2) ◽

pp. 127-134 ◽

Cited By ~ 31

Author(s):

E Altinoz ◽

Z Oner ◽

H Elbe ◽

Y Cigremis ◽

Y Turkoz

Keyword(s):

Plasma Levels ◽

Heart Defects ◽

Ischemia Reperfusion ◽

Kidney Tissue ◽

Kidney Injury ◽

Diabetic Rats ◽

Control Group ◽

Protective Effects ◽

Active Constituent ◽

Hydropic Degeneration

The reactive oxygen species take role in pathogenesis of many diseases including hypoxia, hypercholesterolemia, atherosclerosis, nephropathy, hypertension, ischemia–reperfusion damage, and heart defects. The aim of this study was to evaluate whether crocin administration could protect kidney injury from oxidative stress in streptozotocin-induced diabetic rats. The rats were randomly divided into 3 groups each containing 10 animals as follows: group 1, control group; group 2, diabetes mellitus (DM) group; and group 3, DM + crocin group. At the end of the study, trunk blood was collected to determine the plasma levels of blood urea nitrogen (BUN) and creatinine (Cr). The kidney tissue was removed, and biochemical and histological changes were examined. Diabetes caused a significant increase in malondialdehyde (MDA) and xanthine oxidase (XO) activities and a decrease in glutathione (GSH) contents ( p < 0.01) when compared with control group in the rat kidneys. Crocin given to DM rats significantly decreased MDA ( p < 0.01) and XO ( p < 0.05) activities and elevated GSH ( p < 0.05) contents when compared with DM group. Plasma levels of BUN and Cr were significantly higher in the DM group when compared with the control group ( p < 0.01). Pretreatment of the DM animals with crocin decreased the high level of serum Cr and BUN. Control group was normal in histological appearance, but congestion, severe inflammation, tubular desquamation, tubular necrosis, and hydropic degeneration in tubular cells were observed in the DM group. Histopathological changes markedly reduced, and appearance of kidney was nearly similar to control group in DM + crocin group. Our results show that crocin could be beneficial in reducing diabetes-induced renal injury.

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Protein kinase inhibition differentially regulates organic cation transportThis article is one of a selection of papers published in a special issue celebrating the 125th anniversary of the Faculty of Medicine at the University of Manitoba.

Canadian Journal of Physiology and Pharmacology ◽

10.1139/y09-072 ◽

2009 ◽

Vol 87 (10) ◽

pp. 821-830 ◽

Cited By ~ 2

Author(s):

Alexander M. Gerlyand ◽

Daniel S. Sitar

Keyword(s):

Adenylyl Cyclase ◽

Organic Cation ◽

Kidney Tissue ◽

Organic Cation Transporter ◽

Diabetic Rats ◽

Differential Regulation ◽

Transport Systems ◽

Kidney Cortex ◽

Cellular Transport ◽

Soluble Adenylyl Cyclase

Previous studies showed that amantadine transport increased while tetraethylammonium (TEA) transport decreased in kidney tissue from diabetic rats. Changes in transport activity were reversed by exogenous insulin. We hypothesized that this difference in transport regulation is due to differential regulation of different transport systems. Native human embryonic kidney cortex cells (HEK293 cell line) and rat organic cation transporter (rOCT)-transfected cells were used to test the hypothesis. In support of differential regulation, short-term glucose starvation stimulated amantadine transport and inhibited TEA transport, but the effect was bicarbonate-modulated only for amantadine. cAMP analogues inhibited TEA transport while stimulating amantadine transport. This effect was additive to the effect of insulin, and the presence of bicarbonate affected the extent of the change. Our findings indicated that regulation of rOCT 1 and 2 was mediated by transmembrane adenylyl cyclase, and regulation of amantadine transport was mediated by soluble adenylyl cyclase, suggesting that intracellular microdomains of cAMP may be important in determining overall cellular transport for organic cations. Soluble adenylyl cyclase activity is known to be modulated by bicarbonate and lactate. These observations support our hypothesis and reconcile our previous studies demonstrating increased transport affinity for amantadine in the presence of bicarbonate and decreased transport affinity in the presence of lactate.

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