Hepatoprotective Actions of Ascorbic Acid, Alpha Lipoic Acid and Silymarin or Their Combination Against Acetaminophen-Induced Hepatotoxicity in Rats

Medicina

AnmarM. Abdulrazzaq¹  TawfiqM. Alhussainy¹  NidalA. Qinna¹  Omar Gammoh²  Mujtaba Badr³  AsadA. Abu Khalil³  BayanY. Ghanim³ 

[1] Department of Pharmacology and Biomedical Sciences, Faculty of Pharmacy and Medical Sciences, University of Petra, P.O. Box 961343, Amman 11196, Jordan;Department of Pharmacy, Faculty of Health Sciences, American University of Madaba, P.O. Box 2882, Madaba 11821, Jordan;University of Petra Pharmaceutical Center (UPPC), University of Petra, P.O. Box 961343, Amman 11196, Jordan;

关键词: acetaminophen;    ascorbic acid;    silymarin;    hepatoprotection;    hepatotoxicity;    hepatocytes;    oxidative stress;   

DOI  :  10.3390/medicina55050181

来源: DOAJ

【 摘 要 】

Background and objectives: Ascorbic acid, alpha lipoic acid (ALA) and silymarin are well-known antioxidants that have hepatoprotective effects. This study aims to investigate the effects of these three compounds combined with attenuating drug-induced oxidative stress and cellular damage, taking acetaminophen (APAP)-induced toxicity in rats as a model both in vivo and in vitro. Materials and Methods: Freshly cultured primary rat hepatocytes were treated with ascorbic acid, ALA, silymarin and their combination, both with and without the addition of APAP to evaluate their in vitro impact on cell proliferation and mitochondrial activity. In vivo study was performed on rats supplemented with the test compounds or their combination for one week followed by two toxic doses of APAP. Results: Selected liver function tests and oxidative stress markers including superoxide dismutase (SOD), malondialdehyde (MDA) and oxidized glutathione (GSSG) were detected. The in vivo results showed that all three pretreatment compounds and their combination prevented elevation of SOD and GSSG serum levels indicating a diminished burden of oxidative stress. Moreover, ascorbic acid, ALA and silymarin in combination reduced serum levels of liver enzymes; however, silymarin markedly maintained levels of all parameters to normal ranges. Silymarin either alone or combined with ascorbic acid and ALA protected cultured rat hepatocytes and increased cellular metabolic activity. The subjected agents were capable of significantly inhibiting the presence of oxidative stress induced by APAP toxicity and the best result for protection was seen with the use of silymarin. Conclusions: The measured liver function tests may suggest an augmented hepatoprotection of the combination preparation than when compared individually.

【 授权许可】

Unknown