Effects of calcium channel blockers and hydralazine on plasma glucose levels in streptozotocin-induced diabetic rats in vivo

Plasma glucose levels are maintained by a precise balance between glucose production and its use. Liver pyruvate kinase (PK) and phosphoenolpyruvate carboxykinase (PEPCK), 2 key enzymes of glycolysis and gluconeogenesis, respectively, play a crucial role in this glucose homeostasis along with skeletal muscle glucose transporter (GLUT4). In the diabetic state, this balance is disturbed owing to the absence of insulin, the principal factor controlling this regulation. In the present study, alloxan-diabetic animals having high glucose levels of more than 300 mmol/L have been taken and the administration of Trigonella seed powder (TSP) to the diabetic animals was assessed for its effect on the expression of PK and PEPCK in liver and GLUT4 distribution in skeletal muscle of alloxan-diabetic rats. TSP treatment to the diabetic animals resulted in a marked decrease in the plasma glucose levels. Trigonella treatment partially restored the altered expression of PK and PEPCK. TSP treatment also corrected the alterations in the distribution of GLUT4 in the skeletal muscle.

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Correction to Structure–Activity Relationship, Drug Metabolism and Pharmacokinetics Properties Optimization, and in Vivo Studies of New Brain Penetrant Triple T-Type Calcium Channel Blockers

Journal of Medicinal Chemistry ◽

10.1021/acs.jmedchem.7b00219 ◽

2017 ◽

Vol 60 (5) ◽

pp. 2163-2163

Author(s):

Romain Siegrist ◽

Davide Pozzi ◽

Gaël Jacob ◽

Caterina Torrisi ◽

Kilian Colas ◽

...

Keyword(s):

Drug Metabolism ◽

Calcium Channel ◽

Calcium Channel Blockers ◽

Structure Activity Relationship ◽

In Vivo Studies ◽

Activity Relationship ◽

Channel Blockers ◽

Structure Activity

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Investigation of Calcium Channel Blockers as Antiprotozoal Agents and Their Interference in the Metabolism ofLeishmania (L.) infantum

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2016/1523691 ◽

2016 ◽

Vol 2016 ◽

pp. 1-9 ◽

Cited By ~ 6

Author(s):

Juliana Quero Reimão ◽

Juliana Tonini Mesquita ◽

Daiane Dias Ferreira ◽

Andre Gustavo Tempone

Keyword(s):

Calcium Channel ◽

Chagas Disease ◽

Calcium Channel Blockers ◽

Channel Blockers ◽

Antiprotozoal Activity ◽

Additive Interaction ◽

Therapeutic Class ◽

Species Production

Leishmaniasis and Chagas disease are neglected parasitic diseases endemic in developing countries; efforts to find new therapies remain a priority. Calcium channel blockers (CCBs) are drugs in clinical use for hypertension and other heart pathologies. Based on previous reports about the antileishmanial activity of dihydropyridine-CCBs, this work aimed to investigate whether thein vitroanti-Leishmania infantumand anti-Trypanosoma cruziactivities of this therapeutic class would be shared by other non-dihydropyridine-CCBs. Except for amrinone, our results demonstrated antiprotozoal activity for fendiline, mibefradil, and lidoflazine, with IC50values in a range between 2 and 16 μM and Selectivity Index between 4 and 10. Fendiline demonstrated depolarization of mitochondrial membrane potential, with increased reactive oxygen species production in amlodipine and fendiline treatedLeishmania, but without plasma membrane disruption. Finally,in vitrocombinations of amphotericin B, miltefosine, and pentamidine againstL. infantumshowed in isobolograms an additive interaction when these drugs were combined with fendiline, resulting in overall mean sum of fractional inhibitory concentrations between 0.99 and 1.10. These data demonstrated that non-dihydropyridine-CCBs present antiprotozoal activity and could be useful candidates for futurein vivoefficacy studies against Leishmaniasis and Chagas’ disease.

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