A novel therapeutic combination of dapagliflozin, Lactobacillus and crocin attenuates diabetic cardiomyopathy in rats: Role of oxidative stress, gut microbiota, and PPARγ activation

糖尿病性心肌病 达帕格列嗪 医学 糖尿病 氧化应激 药理学 肠道菌群 化学 番红花苷 内科学 心肌病 内分泌学 2型糖尿病 生物化学 心力衰竭
作者
Eman M. Khalaf,Hanan M. Hassan,Ahmed M. El-Baz,Ahmed Shata,Ahmed E. Khodir,Mahmoud E. Yousef,Rehab Mohamed Elgharabawy,Nehal A. Nouh,Safaa Saleh,Mashael Mohammed Bin-Meferij,Attalla F. El‐kott,Mohamed Mohamed Adel El‐Sokkary,Hanan Eissa
出处
期刊:European Journal of Pharmacology [Elsevier]
卷期号:931: 175172-175172 被引量:13
标识
DOI:10.1016/j.ejphar.2022.175172
摘要

Diabetic cardiomyopathy is diagnosed by the development of abnormality in the structure and performance of myocardium in diabetic mellitus (DM) patients. Recent studies reported the association between altered gut microbiota and metabolic disorders like diabetes and cardiovascular diseases. Here, we aimed to investigate the gut-heart axis in an experimental animal model where we developed a novel therapeutic combination of dapagliflozin, crocin prebiotic and Lactobacilli probiotic to correct induced diabetic cardiomyopathy.Diabetes mellitus was induced by Intraperitoneal (i.p) streptozotocin in male rats. The experimental design includes the administration of the tested drugs (Crocin, Dapagliflozin) solely and with Lactobacillus, or in combination therapy with and without Lactobacillus to the diabetic rats for six weeks. Clinical and microscopic evaluation scoring for cardiac tissues were determined. Biochemical markers including blood glucose level, adiponectin, resistin, cardiac injury markers, lipid profile, antioxidant enzymes, pro and anti-inflammatory markers were assessed. In addition, quantitative relative expression of PPARγ and TXINP genes and capsase-3 levels were measured. The change in the microbiota abundance was investigated using real-time PCR.This study demonstrated the synergistic effect of the triple combination; dapagliflozin, crocin prebiotic, and Lactobacillus fermentum and Lactobacillus delbrueckii probiotic in treating diabetic cardiomyopathy in rats. The triple combination significantly reduced the oxidative, inflammatory, apoptotic activities induced by streptozotocin STZ and helped in restoring the symbiotic gut microbiota.It is worthy to perform this study in clinical trials as a primary step to include crocin and Lactobacilli in the therapeutic protocols of diabetic cardiomyopathy.
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