Trans-sodium crocetinate suppresses apoptotic and oxidative response following myoglobin-induced cytotoxicity in HEK-۲۹۳ cells

Publish Year: 1403
نوع سند: مقاله ژورنالی
زبان: English
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شناسه ملی سند علمی:

JR_IJBMS-27-6_014

تاریخ نمایه سازی: 28 اسفند 1402

Abstract:

Objective(s): Rhabdomyolysis (RM) is a serious fatal syndrome. The RM leads to acute kidney injury (AKI) as a fatal complication. The belief is that RM-induced AKI is triggered by myoglobin (MB). MB activates oxidative and apoptotic pathways. Trans-sodium crocetinate (TSC) is obtained from saffron. It has anti-oxidant and renoprotective effects. This research was designed to assess the mechanisms of MB-induced cytotoxicity in  HEK-۲۹۳ cells (human embryonic kidney cells) as well as the possible effects of TSC against MB-induced cytotoxicity. Materials and Methods: HEK-۲۹۳ cells were exposed to diverse concentrations of TSC (۲.۵, ۵, ۱۰, ۲۰, ۴۰, ۸۰, and ۱۰۰ µM) for ۲۴ hr. Then, MB (۹ mg/ml) was added to the cells. After ۲۴ hr, cell viability was measured through MTT, and the values of ROS generation were calculated using DCFH-DA assay. Also, autophagy and apoptosis markers in cells were assessed by western blot analysis.Results: MB decreased viability and increased ROS levels in HEK-۲۹۳ cells. However, pretreatment of HEK-۲۹۳ cells with TSC for ۲۴ hr reduced the cytotoxicity and ROS production caused by MB. Furthermore, MB enhanced both the apoptosis (cleaved caspase-۳ and Bax/Bcl-۲ ratio) and autophagy markers (LC۳II/I ratio and Beclin-۱) in HEK-۲۹۳ cells. On the other hand, TSC pretreatment condensed the levels of autophagy and apoptosis criteria in response to MB cytotoxicity. Conclusion: TSC has a positive effect in preventing MB-induced cytotoxicity in HEK-۲۹۳ cells by increasing anti-oxidant activity and regulation of apoptotic and autophagy signaling pathways.

Authors

Tahereh Aminifard

Department of Pharmacodynamics and Toxicology, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran

Soghra Mehri

Department of Pharmacodynamics and Toxicology, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran

Mahboobeh Ghasemzadeh Rahbardar

Pharmaceutical Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran

Fatemeh Rajabian

Department of Pharmacodynamics and Toxicology, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran

Abolfazl Khajavirad

Department of Physiology, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran

Hossein Hosseinzadeh

Department of Pharmacodynamics and Toxicology, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran

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