Free radical scavenging decreases endothelin‐1 excretion and glomerular albumin permeability during type 1 diabetes

Saleh, Mohamed A.; Miguel, Carmen De; Stevens, David I.; Carmines, Pamela K.; Pollock, David M.; Pollock, Jennifer S.

doi:10.14814/phy2.13055

Cited by 11 publications

(12 citation statements)

References 53 publications

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“…Additionally, superoxide anions appear to stimulate the production of TXA2 and 8-isoprostane, an equipotent agonist of TP [52, 62] and ET-1 [63, 64]. Thus, pharmacological strategies such as pleiotropic drugs to interrupt this vicious cycle cascade seem to be relevant against AT.…”

Section: Discussionmentioning

confidence: 99%

Sildenafil (Viagra®) Prevents Cox-1/ TXA2 Pathway-Mediated Vascular Hypercontractility in ApoE-/- Mice

Leal

Dias

Porto³

et al. 2017

Cell Physiol Biochem

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Background/Aims: The atherosclerotic apolipoprotein E-deficient (apoE^-/-) mouse exhibits impaired vasodilation and enhanced vasoconstriction responsiveness. The objectives of this study were: a) to determine the relative contribution of cyclooxygenases (Cox-1 and Cox-2), thromboxane A2 (TXA2) and endothelin-1 (ET-1) to enhancing vascular hyperresponsiveness in this model of atherosclerosis and b) to investigate the beneficial effects of the phosphodiesterase 5 inhibitor sildenafil on this endothelial dysfunction. Methods: Adult male apoE^-/- mice were treated with sildenafil (40 mg/kg/day, for 3 weeks) and compared with non-treated ApoE^-/- and wild-type mice. The beneficial effects of sildenafil on vascular contractile response to phenylephrine (PE) in aortic rings were evaluated before and after incubation with Cox-1 (SC-560) or Cox-2 (NS-398) inhibitors or the TP antagonist SQ-29548, and on contractile responsiveness to ET-1. Results: ApoE^-/- mice exhibited enhanced vasoconstriction to PE (R_max ∼35%, p<0.01), which was prevented by treatment with sildenafil. The enhanced PE-induced contractions were abolished by both Cox-1 inhibition and TP antagonist, but were not modified by Cox-2 inhibition. Aortic rings from ApoE^-/- mice also exhibited enhanced contractions to ET-1 (R_max ∼30%, p<0.01), which were attenuated in sildenafil-treated ApoE^-/- mice. In addition, we observed augmented levels of vascular proinflammatory cytokines in ApoE^-/- mice, which were partially corrected by treatment with sildenafil (IL-6, IL-10/IL-6 ratio and MCP-1). Conclusion: The present data show that the Cox-1/TXA2 pathway prevails over the Cox-2 isoform in the mediation of vascular hypercontractility observed in apoE^-/-mice. The results also show a beneficial effect of sildenafil on this endothelial dysfunction and on the proinflammatory cytokines in atherosclerotic animals, opening new perspectives for the treatment of other endothelium-related cardiovascular abnormalities.

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Section: Discussionmentioning

confidence: 99%

Sildenafil (Viagra®) Prevents Cox-1/ TXA2 Pathway-Mediated Vascular Hypercontractility in ApoE-/- Mice

Leal

Dias

Porto³

et al. 2017

Cell Physiol Biochem

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“…Increased proteinuria and albuminuria in diabetic animals are associated with structural protein impairment and glomerular permeability induced by hyperglycemia. 41,42 However, physical exercise prevented the increase of proteinuria and serum creatinine in the rats of the OTD group. In a prior study from our laboratory, aerobic exercise performed pre and postinduction of DM reduced proteinuria in nonovariectomized diabetic rats.…”

Section: Discussionmentioning

confidence: 94%

Preventive effect of exercise training on diabetic kidney disease in ovariectomized rats with type 1 diabetes

Souza

Oliveira

Viana

et al. 2019

Exp Biol Med (Maywood)

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This study evaluated the effects of moderate regular physical exercise on lipid peroxidation, inflammation and renal function and structure in streptozotocin (STZ)-induced ovariectomized diabetic rats. Twenty-four Wistar rats were anesthetized and submitted to bilateral ovariectomy. The rats were divided into four experimental groups: ovariectomized control (OC), ovariectomized trained control (OTC), ovariectomized diabetic (OD), ovariectomized trained diabetic (OTD). The OTD and OTC groups were submitted to treadmill running for four weeks before to diabetes mellitus (DM) induction with STZ (40 mg/kg, i.v) or vehicle injection, respectively, and continued the training for another eight weeks after the injections. Urine samples were collected 24 h after the last training session, and blood samples and kidneys were collected after euthanasia. Our results showed that physical exercise attenuated the loss of body weight and postprandial glucose and improved physical capacity in the OTD group. Lower serum creatinine levels, glycosuria, and proteinuria were also observed in this group. There was no difference in 17β-estradiol levels between the experimental groups. The glomerular and tubulointerstitial changes were attenuated in the OTD group. Expressions of macrophages, lymphocytes, fibronectin, TGF-β1, and NF-κB were reduced in the glomeruli of OTD group. Exercise also reduced macrophages, lymphocytes, and TGF-β1 expression in the tubulointerstitial compartment of the renal cortex of this group. In addition, increased levels of TBARS in the renal cortex of diabetic rats were prevented by exercise in the OTD group. In conclusion, our study shows that physical exercise exerted a renoprotective effect against the progression of diabetic kidney disease in ovariectomized rats. Impact statement To date, no studies have been found evaluating the effects of physical exercise on renal function and structure changes in ovariectomized rats with type 1 diabetes. Therefore, this work emerges with an important tool for strengthening and expanding innovative research on exercise with potential for the prevention of renal diseases in ovariectomized diabetic rats, and future development of studies that seek to increase scientific knowledge about the beneficial effects of physical exercise on renal diseases in humans.

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“…However, exercise training prevented the urinary excretion of proteins in OTD group rats. Increased proteinuria in diabetic animals may be associated with structural protein impairment and glomerular permeability triggered by hyperglycemia (Ito et al, 2015, Wang et al, 2015, Saleh et al, 2016. While beneficial effects of exercise were attributed to the reduction of hyperglycemia, proteinuria and albuminuria, improved bioavailability of nitric oxide and reduction of oxidative stress (Albright et al, 1995;Silva et al, 2012).…”

Section: Discussionmentioning

confidence: 99%

“…Hyperglycemia induces an increase in reactive oxygen species (ROS) and changes in renal structure, suggesting that this may be associated with the development of renal lesions (Mansouri et al, 2011;Punaro et al, 2014;Fernandes et al, 2016). Saleh et al (2016) demonstrated that antioxidant treatment reduced urinary excretion of TBARS, endothelin 1 and glomerular superoxide production, in rats with DM1 induced by estreptozotocin (STZ).…”

Section: Introductionmentioning

confidence: 99%

Effect of moderate exercise on renal changes and oxidative stress in ovariectomized rats with type 1 diabetes mellitus

Silveira¹,

Amaral²,

Souza³

et al. 2019

Braz. J. Biol. Sci.

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This study evaluated the aerobic exercise effects of moderate and progressive intensity on renal function and structure, and oxidative stress in ovariectomized rats with type 1 diabetes mellitus induced by streptozotocin (STZ). Eighteen Wistar rats were divided into 3 groups: OSC - ovariectomized and sedentary control rats; OSD - ovariectomized and sedentary diabetic rats; and OTD - ovariectomized and trained diabetic rats. After induction of diabetes, the OTD group was submitted to eight weeks of exercise. Twenty-four hours after the last training session urine samples were collected. Blood samples and kidneys were collected after euthanasia for renal function analysis, histology, morphometry and oxidative stress. Our results have shown a reduction of the weight gain, increase of kidney weight and postprandial glycemia in diabetic rats. However, exercise decreased glycosuria and prevented the proteinuria in OTD group rats. Focal segmental glomerulosclerosis (FSGS), juxtamedullary glomerular tuft area, tubulointerstitial lesions (TIL), brush border loss and tubular cell debridement were reduced in OTD rats. In addition, exercise training decreased urinary and plasma concentrations of thiobarbituric acid reactive substance (TBARS). Our results demonstrate the beneficial effect of progressive aerobic exercise on proteinuria, glycosuria, and renal structure in ovariectomized diabetic rats, which may be mediated in part by reduction of oxidative stress.

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Free radical scavenging decreases endothelin‐1 excretion and glomerular albumin permeability during type 1 diabetes

Cited by 11 publications

References 53 publications

Sildenafil (Viagra®) Prevents Cox-1/ TXA2 Pathway-Mediated Vascular Hypercontractility in ApoE-/- Mice

Sildenafil (Viagra®) Prevents Cox-1/ TXA2 Pathway-Mediated Vascular Hypercontractility in ApoE-/- Mice

Preventive effect of exercise training on diabetic kidney disease in ovariectomized rats with type 1 diabetes

Effect of moderate exercise on renal changes and oxidative stress in ovariectomized rats with type 1 diabetes mellitus

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