Cytoprotective effects of silafibrate, a newly-synthesised siliconated derivative of clofibrate, against acetaminophen‑induced toxicity in isolated rat hepatocytes
Sara Nafisi
; Biotechnology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
Reza Heidari
; Pharmaceutical Sciences
Mohammad Ghaffarzadeh
; Chemistry and Chemical Engineering Research Center of Iran, Tehran, Iran
Mojtaba Ziaee
; Biotechnology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
Hossein Hamzeiy
; Biotechnology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
Alireza Garjani
; Drug Applied Research Center Tabriz University of Medical Sciences, Tabriz,, Iran
Mohammad Ali Eghbal
; Tabriz University of Medical Sciences Pharmacology and Toxicology Department School of Pharmacy, Tabiz, Iran
APA 6th Edition Nafisi, S., Heidari, R., Ghaffarzadeh, M., Ziaee, M., Hamzeiy, H., Garjani, A. i Eghbal, M.A. (2014). Cytoprotective effects of silafibrate, a newly-synthesised siliconated derivative of clofibrate, against acetaminophen‑induced toxicity in isolated rat hepatocytes. Arhiv za higijenu rada i toksikologiju, 65 (2), 169-177. https://doi.org/10.2478/10004-1254-65-2014-2434
MLA 8th Edition Nafisi, Sara, et al. "Cytoprotective effects of silafibrate, a newly-synthesised siliconated derivative of clofibrate, against acetaminophen‑induced toxicity in isolated rat hepatocytes." Arhiv za higijenu rada i toksikologiju, vol. 65, br. 2, 2014, str. 169-177. https://doi.org/10.2478/10004-1254-65-2014-2434. Citirano 11.04.2021.
Chicago 17th Edition Nafisi, Sara, Reza Heidari, Mohammad Ghaffarzadeh, Mojtaba Ziaee, Hossein Hamzeiy, Alireza Garjani i Mohammad Ali Eghbal. "Cytoprotective effects of silafibrate, a newly-synthesised siliconated derivative of clofibrate, against acetaminophen‑induced toxicity in isolated rat hepatocytes." Arhiv za higijenu rada i toksikologiju 65, br. 2 (2014): 169-177. https://doi.org/10.2478/10004-1254-65-2014-2434
Harvard Nafisi, S., et al. (2014). 'Cytoprotective effects of silafibrate, a newly-synthesised siliconated derivative of clofibrate, against acetaminophen‑induced toxicity in isolated rat hepatocytes', Arhiv za higijenu rada i toksikologiju, 65(2), str. 169-177. https://doi.org/10.2478/10004-1254-65-2014-2434
Vancouver Nafisi S, Heidari R, Ghaffarzadeh M, Ziaee M, Hamzeiy H, Garjani A i sur. Cytoprotective effects of silafibrate, a newly-synthesised siliconated derivative of clofibrate, against acetaminophen‑induced toxicity in isolated rat hepatocytes. Arh Hig Rada Toksikol. [Internet]. 2014 [pristupljeno 11.04.2021.];65(2):169-177. https://doi.org/10.2478/10004-1254-65-2014-2434
IEEE S. Nafisi, et al., "Cytoprotective effects of silafibrate, a newly-synthesised siliconated derivative of clofibrate, against acetaminophen‑induced toxicity in isolated rat hepatocytes", Arhiv za higijenu rada i toksikologiju, vol.65, br. 2, str. 169-177, 2014. [Online]. https://doi.org/10.2478/10004-1254-65-2014-2434
Sažetak Acetaminophen (N-acetyl para amino phenol, APAP) is a widely used antipyretic and analgesic drug responsible for various drug-induced liver injuries. This study evaluated APAP-induced toxicity in isolated rat hepatocytes alongside the protective effects of silafibrate and N-acetyl cysteine (NAC). Hepatocytes were isolated from male Sprague-Dawley rats by collagenase enzyme perfusion via the portal vein. This technique is based on liver perfusion with collagenase after removing calcium ions (Ca2+) with a chelator. Cells were treated with different concentrations of APAP, silafibrate, and NAC. Cell death, reactive oxygen species (ROS) formation, lipid peroxidation, and mitochondrial depolarisation were measured as toxicity markers. ROS formation and lipid peroxidation occurred after APAP administration to rat hepatocytes. APAP caused mitochondrial depolarisation in isolated cells. Administration of silafibrate (200 μmol L-1) and/or NAC (200 μmol L-1) reduced the ROS formation, lipid peroxidation, and mitochondrial depolarisation caused by APAP. Cytotoxicity induced by APAP in rat hepatocytes was mediated by oxidative stress. In addition, APAP seemed to target cellular mitochondria during hepatocyte damage. The protective properties of silafibrate and/or NAC against APAP‑induced hepatic injury may have involved the induction of antioxidant enzymes, protection against oxidative stress and inflammatory responses, and alteration in cellular glutathione content.