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苯磷硫胺,一种 NADPH 氧化酶抑制剂,对异丙肾上腺素诱导的大鼠心肌梗死的有益作用。

Beneficial effects of benfotiamine, a NADPH oxidase inhibitor, in isoproterenol-induced myocardial infarction in rats.

机构信息

Department of Pharmacology and Toxicology, Faculty of Pharmacy, Cairo University, Giza, Egypt.

Department of Pharmacology and Toxicology, Faculty of Pharmacy, MSA University, 6th of October City, Egypt.

出版信息

PLoS One. 2020 May 8;15(5):e0232413. doi: 10.1371/journal.pone.0232413. eCollection 2020.

Abstract

BACKGROUND

Acute myocardial infarction (AMI) remains the most common cause of morbidity and mortality worldwide. The present study was directed to investigate the beneficial effects of benfotiamine pre- and post-treatments in isoproterenol (ISO)-induced MI in rats.

METHODS

Myocardial heart damage was induced by subcutaneous injection of ISO (150 mg/kg) once daily for two consecutive days. Benfotiamine (100 mg/kg/day) was given orally for two weeks before or after ISO treatment.

RESULTS

ISO administration revealed significant changes in electrocardiographic recordings, elevation of levels of cardiac enzymes; creatinine kinase (CK-MB) and troponin-I (cTn-I), and perturbation of markers of oxidative stress; nicotinamide adenine dinucleotide phosphate (NADPH) oxidase, malondialdehyde (MDA), reduced glutathione (GSH), superoxide dismutase (SOD) and glutathione peroxidase (GPx) and markers of inflammation; protein kinase C (PKC), nuclear factor-kappa B (NF-κB) and metalloproteinase-9 (MMP-9). The apoptotic markers (caspase-8 and p53) were also significantly elevated in ISO groups in addition to histological alterations. Groups treated with benfotiamine pre- and post-ISO administration showed significantly decreased cardiac enzymes levels and improved oxidative stress, inflammatory and apoptotic markers compared to the ISO groups.

CONCLUSION

The current study highlights the potential role of benfotiamine as a promising agent for prophylactic and therapeutic interventions in myocardial damage in several cardiovascular disorders via NADPH oxidase inhibition.

摘要

背景

急性心肌梗死(AMI)仍然是全球发病率和死亡率最高的疾病。本研究旨在探讨苯磷硫胺素预处理和后处理对异丙肾上腺素(ISO)诱导的大鼠心肌梗死的有益作用。

方法

通过皮下注射 ISO(150mg/kg),每天一次,连续两天,诱导心肌损伤。苯磷硫胺素(100mg/kg/天)在 ISO 处理前或后口服给药两周。

结果

ISO 给药后心电图记录、心脏酶水平升高;肌酸激酶同工酶(CK-MB)和肌钙蛋白 I(cTn-I),氧化应激标志物紊乱;烟酰胺腺嘌呤二核苷酸磷酸(NADPH)氧化酶、丙二醛(MDA)、还原型谷胱甘肽(GSH)、超氧化物歧化酶(SOD)和谷胱甘肽过氧化物酶(GPx)和炎症标志物;蛋白激酶 C(PKC)、核因子-κB(NF-κB)和金属蛋白酶-9(MMP-9)。ISO 组还显著升高了凋亡标志物(caspase-8 和 p53),此外还存在组织学改变。与 ISO 组相比,苯磷硫胺素预处理和后处理组的心脏酶水平显著降低,氧化应激、炎症和凋亡标志物得到改善。

结论

本研究强调了苯磷硫胺素作为一种有前途的预防和治疗多种心血管疾病心肌损伤的药物的潜力,其作用机制可能与 NADPH 氧化酶抑制有关。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/92f8/7209119/98b8c42e0f70/pone.0232413.g001.jpg

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