Drug Design, Development and Therapy (Oct 2018)
Antioxidative stress effects of vitamins C, E, and B12, and their combination can protect the liver against acetaminophen-induced hepatotoxicity in rats
Abstract
Farah M Abdulkhaleq,1 Tawfiq M Alhussainy,1 Mujtaba M Badr,2 Asad A Abu Khalil,2 Omar Gammoh,3 Bayan Y Ghanim,2 Nidal A Qinna1,2 1Department of Pharmacology and Biomedical Sciences, Faculty of Pharmacy and Medical Sciences, University of Petra, Amman, Jordan; 2University of Petra Pharmaceutical Center (UPPC), University of Petra, Amman, Jordan; 3Department of Pharmacy, Faculty of Health Sciences, American University of Madaba, Madaba, Jordan Background: Several vitamins, including C, E, and B12, have been recognized as antioxidants and have shown hepatoprotective effects against the hepatotoxicity caused by acetaminophen (APAP) overdose. The current investigation aims to study the effect of these vitamins and their combination in protecting the liver from APAP hepatotoxicity in rats. Materials and methods: An in vitro model of freshly isolated rat hepatocytes was utilized for assessing hepatocyte mitochondrial activity conducted by cell proliferation assay (MTT). The isolated hepatocytes were treated with vitamin C, vitamin E, vitamin B12 and their combination, with and without further addition of toxic concentrations of APAP. In addition, an in vivo experiment was carried out on Sprague Dawley rats treated intraperitoneally for 8 days with emulsions of the vitamins or their combination prior to injecting them with APAP. Results: In vitro results showed that vitamins C and B and the combination preparation significantly increased the percentage of hepatocyte mitochondrial activity, both with and without the addition of APAP (P<0.01). The mitochondrial activity in the isolated cultured hepatocytes was further enhanced with APAP addition. In vivo, the vitamins and their combination effectively reduced APAP-induced serum liver enzymes levels, namely ALT, AST, and ALP, and also attenuated oxidative stress and lipids peroxidation confirmed by the results of glutathione, superoxide dismutase, and maloondialdehyde. Conclusion: Pretreatment with vitamins C, E, B12, or their combination was found to be beneficial in preventing in vivo hepatic oxidative stress induced by APAP overdose. Vitamin C on its own showed superior protection against APAP-induced liver injury in rats compared to the other vitamins. The proliferation of APAP-intoxicated liver cells in vitro was highest when protected with the vitamins’ combination. Keywords: glutathione, hepatocytes, proliferation, hepatoprotective, superoxide dismutase, primary cell culture
