Effects of N-acetyl cysteine, vitamin E and vitamin C on liver glutathione levels following amiodarone treatment in rats

Abstract

Introduction Amiodarone, a pharmaceutical extensively used to suppress atrial and ventricular tachyarrhythmias, is also known to cause many side effects on many tissues. N-acetyl-cysteine (NAC), vitamin E and vitamin C are known as antioxidants for their ability to minimize oxidative stress. In the peer-reviewed literature, there is no study reporting on the protective effects of these antioxidant agents against its hepatotoxicity. Aim We investigated the oxidative effects of NAC, vitamins E and C on liver tissue after amiodarone treatment. Material and methods Rats were randomly assigned to: control; amiodarone group; amiodarone + NAC treated group; amiodarone + Vit. E group and amiodarone + Vit. C group. Liver tissues were isolated from animals and total glutathione levels were measured. Results In all time intervals, the level of glutathione increased. When all time intervals were compared, the amiodarone group revealed the lowest levels. The antioxidant co-administered group was studied; the glutathione levels were statistically significantly higher than the sole amiodarone group. When vitamins E, C or N-acetyl cysteine were examined, there was no statistically significant difference among them. Conclusions In this study we found that hepatotoxicity capacity of amiodarone may be reduced by taking up antioxidants. In addition, the effect documented here may be reproducible and may be applied to clinical settings.

Drug-induced Fatty Liver Disease: Pathogenesis and Treatment

“…The main mechanisms in the development of DIFLD are thought to include lipogenesis and generation of free radicals leading to oxidative stress induction in hepatocytes. 44,75 Kim et al 76 showed that amiodarone caused an increase in short, medium-and long-chain acylcarnitines in the livers of rats, with the highest increases involving levels of acetylcarnitine. The most probable cause of these disturbances in liver tissue is the effect of amiodarone on mtFAO by blocking the activity of the carnitine palmitoyltransferase-1 enzyme, thereby directly inhibiting the mitochondrial β-oxidation of acyl-CoA to acetyl-CoA and by inhibiting complexes I and II of the MRC.…”

“…Like amiodarone, it causes a reduction in liver glutathione levels, accumulation of oxidized form of glutathione, and lipid peroxidation. 75,81 Methotrexate and especially its polyglutamated metabolite are both stored in hepatocytes and exert hepatotoxic effects. 82 Several mechanisms are proposed for the hepatotoxic effect of methotrexate, including hampering of folate entry to mitochondria, which leads to mitochondrial dysfunction and generation of ROS and finally induction of caspase-dependent apoptosis.…”

“…One of those is a pediatric report of amoxicillin/clavulanic acid toxicity 4 years after the liver transplantation. Amelioration 75 Further clinical trials on humans are needed to confirm these observations.…”

“…The main mechanisms in the development of DIFLD are thought to include lipogenesis and generation of free radicals leading to oxidative stress induction in hepatocytes. 44 , 75 Kim et al . 76 showed that amiodarone caused an increase in short, medium- and long-chain acylcarnitines in the livers of rats, with the highest increases involving levels of acetylcarnitine.…”

“…Like amiodarone, it causes a reduction in liver glutathione levels, accumulation of oxidized form of glutathione, and lipid peroxidation. 75 , 81 …”