Resveratrol alleviates cardiac apoptosis following exposure to fenitrothion by modulating the sirtuin1/c-Jun N-terminal kinases/p53 pathway through pro-oxidant and inflammatory response improvements: In vivo and in silico studies

• Published in: Life sciences (1973) Vol. 290; p. 120265
• Main Authors: Ibrahim, Khairy A., Abdelgaid, Hala A., Eleyan, Mohammed, Mohamed, Rania A., Gamil, Noha M.
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier Inc 01.02.2022; Elsevier BV
• Subjects: Acetylcholinesterase; Acetylcholinesterase - metabolism; Animals; Antioxidants - metabolism; Apoptosis; Apoptosis - drug effects; c-Jun protein; Calcium-binding protein; Cardiac oxidative stress; Cardiotoxicity - drug therapy; Caspase-9; Catalase; Creatine; Creatine kinase; Cytokines; Deoxyribonucleic acid; DNA; Fenitrothion; Fenitrothion - adverse effects; Fenitrothion - pharmacology; Fenitrothion - toxicity; Gene sequencing; Glutathione; Glutathione - metabolism; Glutathione reductase; Heart; Hyperlipidemia; Immunoreactivity; In vivo methods and tests; Inflammation; Inflammatory response; Injury prevention; Interleukin 1; Interleukin 6; Intoxication; JNK Mitogen-Activated Protein Kinases - metabolism; JNK protein; Kinases; L-Lactate dehydrogenase; Lactate dehydrogenase; Lactic acid; Male; Males; Malondialdehyde; Myocytes, Cardiac - drug effects; Myocytes, Cardiac - metabolism; Nucleotide sequence; Organophosphates; Organs; Oxidation-Reduction; Oxidative Stress; Oxidizing agents; Rats; Reactive Oxygen Species - metabolism; Reductases; Resveratrol; Resveratrol - metabolism; Resveratrol - pharmacology; Signal Transduction; Sirtuin 1 - metabolism; Sirtuin1/c-Jun N-terminal kinase/p53; Superoxide dismutase; Superoxide Dismutase - metabolism; Transcription factors; Tumor necrosis factor-TNF; Tumor Suppressor Protein p53 - metabolism; Inflammation; Cardiac oxidative stress; Fenitrothion; Resveratrol; Sirtuin1/c-Jun N-terminal kinase/p53; Apoptosis
• ISSN: 0024-3205; 1879-0631
• DOI: 10.1016/j.lfs.2021.120265

Fenitrothion (FNT), a commonly used organophosphate, can cause oxidative damage and apoptosis on various organs. However, the underlying mechanisms for FNT-induced cardiotoxicity did not formally report. Here, we have evaluated the possible ameliorative roles of resveratrol (RSV) against FNT-induced cardiac apoptosis in male rats through the sirtuin1 (SIRT1)/c-Jun N-terminal kinase (c-JNK)/p53 pathway concerning pro-oxidant and inflammatory cytokines. Forty-eight male rats were equally grouped into control, RSV (20 mg/kg), 5-FNT (5 mg/kg), 10-FNT (10 mg/kg), 20-FNT (20 mg/kg), 5-FNT-RSV, 10-FNT-RSV, and 20-FNT-RSV where all doses administrated by gavage for four weeks. The present findings demonstrated that RSV markedly diminished the level of hyperlipidemia and elevation in lactate dehydrogenase (LDH), total creatine kinase (CK-T), and troponin T (TnT) levels following FNT intoxication. Furthermore, RSV significantly reduced FNT-induced cardiac oxidative injury by reducing malondialdehyde (MDA) level and improving the levels of glutathione (GSH), glutathione reductase (GR), superoxide dismutase (SOD), catalase (CAT), and acetylcholinesterase (AchE). Also, the levels of interleukin-1β (IL1β,), tumor necrosis factor-α (TNF-α), and interleukin-6 (IL-6) were significantly attenuated in the co-treated groups. Moreover, RSV alleviated the histopathological changes promoted by FNT and repaired the transcript levels of SIRT1, c-JNK, and caspase-9/3 along with p53 immunoreactivity. In silico study revealed that the free binding energies of RSV complexes with protein and DNA sequences of SIRT1 were lower than docked complexes of FNT. Therefore, RSV reserved myocardial injury-induced apoptosis following exposure to FNT by modulating the SIRT1/c-JNK/p53 pathway through cellular redox status and inflammatory response improvements. [Display omitted] •Resveratrol reduced hyperlipidemia and elevated cardiac biomarker levels induced by fenitrothion.•Resveratrol alleviated fenitrothion-induced cardiac oxidative injury and inflammatory responses.•The binding energies of resveratrol with sirtuin1 were lower than fenitrothion.•Resveratrol protected from cardiac apoptosis by modulating the sirtuin1/c-Jun N-terminal kinases/p53 pathway.