Thymoquinone alleviates mitochondrial viability and apoptosis in diclofenac-induced acute kidney injury (AKI) via regula
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RESEARCH ARTICLE
Thymoquinone alleviates mitochondrial viability and apoptosis in diclofenac-induced acute kidney injury (AKI) via regulating Mfn2 and miR-34a mRNA expressions Khalid Shaaban Hashem 1 & Ahmed Zakaria Abdelazem 2 & Marwa Abdeltawab Mohammed 3 & Amr M. Nagi 2 & Basma Emad Aboulhoda 4 & Eman T. Mohammed 1 & Mohamed M. Abdel-Daim 5,6 Received: 24 April 2020 / Accepted: 18 October 2020 # Springer-Verlag GmbH Germany, part of Springer Nature 2020
Abstract The current study was prepared to assess the underlying mechanism of diclofenac (Diclo)-stimulated renal oxidative damage (50 mg/kg/day for two consecutive days I.P) and antioxidative, and antiapoptotic effects of Thymoquinone (20 mg/kg/day for 21 days P.O). Exposure of rats to Diclo significantly increased serum urea and creatinine, decreased GSH, catalase, and total antioxidant capacity with a concomitant increase of lipid peroxidation. Diclo significantly decreased renal mitochondrial viability %, increased DNA fragmentation %, caspase 3 activity, and cytochrome C (Cyt C) concentration. Molecular investigations revealed that Diclo administration caused a significant reduction of mitofusin-2 (Mfn2) and increase of microRNA-34a (miR34a) mRNA expressions with a concomitant decrease of Nrf2 and HO-1 mRNA expressions/protein levels and increase of NF-κB mRNA expressions. Thymoquinone restored renal oxidative/antioxidant redox. Thymoquinone significantly increased the renal mitochondrial viability % and reduced renal DNA fragmentation %, caspase 3 activity, and Cyt C. Moreover, thymoquinone modulated renal Mfn2 and miR-34a as compared to Diclo group. Our findings were confirmed by immunohistochemical assays for detecting the iNOS and NOX4 in renal tissue as well as histopathological investigations. Obtained results demonstrated that thymoquinone possess a potential antioxidant, antiapoptotic defense and exhibited a strong nephroprotective activity against Diclo-induced toxicity. Keywords Mfn2 . miR-34a . Nephrotoxicity . Diclofenac and thymoquinone
Introduction Responsible Editor: Philippe Garrigues * Khalid Shaaban Hashem [email protected] 1
Biochemistry Department, Faculty of Veterinary Medicine, Beni-Suef University, Beni-Suef 62511, Egypt
2
Biotechnology and Life Sciences Department, Faculty of Postgraduate Studies for Advanced Sciences, Beni-Suef University, Beni-Suef, Egypt
3
Physiology Department, Faculty of Medicine, Beni-Suef University, Beni-Suef, Egypt
4
Department of Anatomy and Embryology, Faculty of Medicine, Cairo University, Cairo, Egypt
5
Department of Zoology, College of Science, King Saud University, P.O. Box 2455, Riyadh 11451, Saudi Arabia
6
Pharmacology Department, Faculty of Veterinary Medicine, Suez Canal University, 41522 Ismailia, Egypt
The kidney plays several important roles in the body, for example, the excretion of endogenous waste metabolites, the regulation of blood volume, electrolytes, acid base balance, and hormonal function. In specific, the kidney performs a vital function in urine formation a
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