Effect of bis-1,4-Dihydropyridine in the Kidney of Diabetic Rats
The in vivo effectiveness of 4-dihydropyridine (bis-1,4-DHP), a new calcium-channel blocker, as a nephroprotector in isolated perfused kidney was evaluated by determining its effects on parameters associated with renal injury in diabetic rats. Diabetes in male Wistar rats, control, diabetic, control...
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Elsevier
2013-01-01
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Series: | Journal of Pharmacological Sciences |
Online Access: | http://www.sciencedirect.com/science/article/pii/S134786131930310X |
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author | Raquel Gómez-Pliego Jaime Gómez-Zamudio Benjamín Velasco-Bejarano Maximiliano Ibarra-Barajas Rafael Villalobos-Molina |
author_facet | Raquel Gómez-Pliego Jaime Gómez-Zamudio Benjamín Velasco-Bejarano Maximiliano Ibarra-Barajas Rafael Villalobos-Molina |
author_sort | Raquel Gómez-Pliego |
collection | DOAJ |
description | The in vivo effectiveness of 4-dihydropyridine (bis-1,4-DHP), a new calcium-channel blocker, as a nephroprotector in isolated perfused kidney was evaluated by determining its effects on parameters associated with renal injury in diabetic rats. Diabetes in male Wistar rats, control, diabetic, control + bis-1,4-DHP, and diabetic + bis-1,4-DHP, was induced by a single administration of STZ (55 mg×kg−1, i.p.). In the drug-treated groups, treatment with bis-1,4-DHP (10 mg×kg−1×day−1) started one week before diabetes induction; bis-1,4-DHP was dissolved in DMSO (0.3%) and suspended in drinking water with carboxymethyl cellulose (3%). Parameters evaluated were body weight, blood glucose, albuminuria, proteinuria, creatinine, urea excretion, kidney’s weight / body weight ratio, and kidney perfusion pressure in all rat groups at different times of diabetes (2, 4, 6, and 10 weeks). Kidney weight of diabetic rats significantly increased vs. control, control + bis-1,4-DHP, and diabetic + bis-1,4-DHP rats at different times of diabetes. The ratios % kidney weight / 100 g body weight were different between control, control + bis-1,4-DHP, and diabetic + bis-1,4-DHP rats vs. diabetic rats (P < 0.05). Kidney perfusion pressure was decreased by diabetes, while it was partially recovered by bis-1,4-DHP treatment in response to phenylephrine. Bis-1,4-DHP had a tendency to decrease hyperglycemia vs. diabetic rats, even though glycemia was too high as compared with controls, and it ameliorated albuminuria, creatinine, and urea excretion, suggesting a favorable effect on renal haemodynamics. Bis-1,4-DHP, by inhibiting Ca2+ entrance, induced vasodilation in renal vascular bed and thus may have a nephroprotective effect against diabetes-induced renal dysfunction, but does not have significant impact on hyperglycemia. Keywords:: bis-1,4-dihydropirydine derivative, calcium-channel blocker, nephoprotector, diabetes, kidney |
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spelling | doaj.art-f9a16ebac94b492580df5ba2e04fa9d82022-12-21T23:55:24ZengElsevierJournal of Pharmacological Sciences1347-86132013-01-011223184192Effect of bis-1,4-Dihydropyridine in the Kidney of Diabetic RatsRaquel Gómez-Pliego0Jaime Gómez-Zamudio1Benjamín Velasco-Bejarano2Maximiliano Ibarra-Barajas3Rafael Villalobos-Molina4Biological Sciences and Human Health Section, Department of Biological Sciences, National Autonomous University of México, Ave. de los Barrios 1, Los Reyes Iztacala, Tlalnepantla, 54090, México; Biomedicine Unit, Faculty of Higher Studies Iztacala, National Autonomous University of México, Ave. de los Barrios 1, Los Reyes Iztacala, Tlalnepantla, 54090, México; Corresponding author. ragopli@yahoo.com.mxBiomedicine Unit, Faculty of Higher Studies Iztacala, National Autonomous University of México, Ave. de los Barrios 1, Los Reyes Iztacala, Tlalnepantla, 54090, MéxicoOrganic Chemistry Section, Department of Chemical Sciences, Faculty of Higher Studies Cuautitlan, National Autonomous University of México, Ave. 1 de Mayo s/n, Santa María las Torres, Cuautitlán Izcalli, 54740, MéxicoBiomedicine Unit, Faculty of Higher Studies Iztacala, National Autonomous University of México, Ave. de los Barrios 1, Los Reyes Iztacala, Tlalnepantla, 54090, MéxicoBiomedicine Unit, Faculty of Higher Studies Iztacala, National Autonomous University of México, Ave. de los Barrios 1, Los Reyes Iztacala, Tlalnepantla, 54090, MéxicoThe in vivo effectiveness of 4-dihydropyridine (bis-1,4-DHP), a new calcium-channel blocker, as a nephroprotector in isolated perfused kidney was evaluated by determining its effects on parameters associated with renal injury in diabetic rats. Diabetes in male Wistar rats, control, diabetic, control + bis-1,4-DHP, and diabetic + bis-1,4-DHP, was induced by a single administration of STZ (55 mg×kg−1, i.p.). In the drug-treated groups, treatment with bis-1,4-DHP (10 mg×kg−1×day−1) started one week before diabetes induction; bis-1,4-DHP was dissolved in DMSO (0.3%) and suspended in drinking water with carboxymethyl cellulose (3%). Parameters evaluated were body weight, blood glucose, albuminuria, proteinuria, creatinine, urea excretion, kidney’s weight / body weight ratio, and kidney perfusion pressure in all rat groups at different times of diabetes (2, 4, 6, and 10 weeks). Kidney weight of diabetic rats significantly increased vs. control, control + bis-1,4-DHP, and diabetic + bis-1,4-DHP rats at different times of diabetes. The ratios % kidney weight / 100 g body weight were different between control, control + bis-1,4-DHP, and diabetic + bis-1,4-DHP rats vs. diabetic rats (P < 0.05). Kidney perfusion pressure was decreased by diabetes, while it was partially recovered by bis-1,4-DHP treatment in response to phenylephrine. Bis-1,4-DHP had a tendency to decrease hyperglycemia vs. diabetic rats, even though glycemia was too high as compared with controls, and it ameliorated albuminuria, creatinine, and urea excretion, suggesting a favorable effect on renal haemodynamics. Bis-1,4-DHP, by inhibiting Ca2+ entrance, induced vasodilation in renal vascular bed and thus may have a nephroprotective effect against diabetes-induced renal dysfunction, but does not have significant impact on hyperglycemia. Keywords:: bis-1,4-dihydropirydine derivative, calcium-channel blocker, nephoprotector, diabetes, kidneyhttp://www.sciencedirect.com/science/article/pii/S134786131930310X |
spellingShingle | Raquel Gómez-Pliego Jaime Gómez-Zamudio Benjamín Velasco-Bejarano Maximiliano Ibarra-Barajas Rafael Villalobos-Molina Effect of bis-1,4-Dihydropyridine in the Kidney of Diabetic Rats Journal of Pharmacological Sciences |
title | Effect of bis-1,4-Dihydropyridine in the Kidney of Diabetic Rats |
title_full | Effect of bis-1,4-Dihydropyridine in the Kidney of Diabetic Rats |
title_fullStr | Effect of bis-1,4-Dihydropyridine in the Kidney of Diabetic Rats |
title_full_unstemmed | Effect of bis-1,4-Dihydropyridine in the Kidney of Diabetic Rats |
title_short | Effect of bis-1,4-Dihydropyridine in the Kidney of Diabetic Rats |
title_sort | effect of bis 1 4 dihydropyridine in the kidney of diabetic rats |
url | http://www.sciencedirect.com/science/article/pii/S134786131930310X |
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