Vitamin D3 potentiates the renoprotective effects of vildagliptin in a rat model of fructose/salt-induced insulin resistance

Autor: Salah A. Ghareib, Amira E Alsemeh, Nehal S. Wahba, Mohamed Abdel-Aal, Rasha H. Abdelghany
Rok vydání: 2019
Předmět:
Blood Glucose
Male
Pharmaceutical Science
02 engineering and technology
Pharmacology
AMP-Activated Protein Kinases
Sodium Chloride
medicine.disease_cause
Kidney
030226 pharmacology & pharmacy
chemistry.chemical_compound
0302 clinical medicine
Sirtuin 1
Glucagon-Like Peptide 1
Malondialdehyde
Urea
Vildagliptin
Hyperuricemia
Cholecalciferol
021001 nanoscience & nanotechnology
Creatinine
0210 nano-technology
medicine.drug
Compensatory Hyperinsulinemia
Vitamin
Kidney Cortex
MAP Kinase Signaling System
Receptor
Angiotensin
Type 1
Nephropathy
Transforming Growth Factor beta1
03 medical and health sciences
Insulin resistance
medicine
Animals
Hypoglycemic Agents
Rats
Wistar
Dipeptidyl peptidase-4
Dipeptidyl-Peptidase IV Inhibitors
business.industry
Tumor Necrosis Factor-alpha
medicine.disease
Rats
Uric Acid
Oxidative Stress
chemistry
Insulin Resistance
business
Oxidative stress
NADP
Zdroj: European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences. 144
ISSN: 1879-0720
Popis: Insulin resistance (IR) seemingly plays a role in chronic kidney disease (CKD). The present study has elucidated the crucial interplay of oxidative stress, inflammatory, apoptotic and profibrotic signaling pathways, linking IR to CKD. The study aimed at investigating the pleiotropic nephroprotective effects of either vildagliptin or vitamin D3 in a fructose/salt-induced IR rat model, highlighting the potential molecular mechanisms underlying their action. Another interesting target was to evaluate the potential capacity of vitamin D3 to potentiate the nephroprotective effects of vildagliptin. Indeed, a state of impaired fasting glucose, IR and compensatory hyperinsulinemia, constellating with significant weight gain, atherogenic dyslipidemia and hyperuricemia was established 6 weeks after fructose/salt consumption. IR rats were then treated orally with vildagliptin (10 mg/kg/day), vitamin D3 (10 µg/kg/day) or their combination for a further 6 weeks. By the end of the 12th week, untreated IR rats displayed significantly declined renal function with parallel interwined renal oxidative stress, inflammatory, apoptotic and profibrotic changes, renal histopathological damages and markedly enhanced collagen fiber deposition. Vildagliptin and vitamin D3 reversed hyperuricemia and exerted a plethora of renal anti-oxidant, anti-inflammatory, anti-apoptotic and anti-fibrotic effects. Our study has introduced a new insight into the role of dipeptidyl peptidase-4 inhibition and silent information regulator 1/5′adenosine monophosphate-activated protein kinase activation in the nephroprotective effects of either agent, elucidating their possible crosstalk with renin angiotensin aldosterone system downregulation. Considering the superadditive renoprotective effects evoked by the combination, vitamin D3 is worth being further investigated as an additional therapeutic agent for preventing IR-induced nephropathy.
Databáze: OpenAIRE
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