Oxidative Stress and Inflammation in Hepatic Diseases: Therapeutic Possibilities of N-Acetylcysteine

Abstract

Liver disease is highly prevalent in the world. Oxidative stress (OS) and inflammation are the most important pathogenetic events in liver diseases, regardless the different etiology and natural course. N-acetyl-l-cysteine (the active form) (NAC) is being studied in diseases characterized by increased OS or decreased glutathione (GSH) level. NAC acts mainly on the supply of cysteine for GSH synthesis. The objective of this review is to examine experimental and clinical studies that evaluate the antioxidant and anti-inflammatory roles of NAC in attenuating markers of inflammation and OS in hepatic damage. The results related to the supplementation of NAC in any form of administration and type of study are satisfactory in 85.5% (n = 59) of the cases evaluated (n = 69, 100%). Within this percentage, the dosage of NAC utilized in studies in vivo varied from 0.204 up to 2 g/kg/day. A standard experimental design of protection and treatment as well as the choice of the route of administration, with a broader evaluation of OS and inflammation markers in the serum or other biological matrixes, in animal models, are necessary. Clinical studies are urgently required, to have a clear view, so that, the professionals can be sure about the effectiveness and safety of NAC prescription.

The Effects of Subchronic Methionine Overload Administered Alone or Simultaneously with L-cysteine or N-acetyl-L-cysteine on Body Weight, Homocysteine Levels and Biochemical Parameters in the Blood of Male Wistar Rats

“…With the help of choline and inositol, methionine prevents fat accumulation in the liver. In our research, methionine also led to a decrease in hepatic lipid levels, although the decrease was not significant, possibly due to the shorter administration period compared to other studies (49). When compared to cysteine in another study, methionine inhibited the accumulation of fat to a higher degree; this result was also confirmed by our findings (50).…”

Molecular cloning, characterization, and the response of Cu/Zn superoxide dismutase and catalase to PBDE-47 and -209 from the freshwater bivalve Anodonta woodiana

“…On another hand, A. woodiana also adjust it's antioxidant ability by enhancing antioxidant enzyme expression to eliminate ROS. If generation of ROS are under a weak level, anti-oxidant enzyme expressions should be up-regulated that contribute to endure oxidative stresses [25,26,39,44]. Once the production of ROS is exceed the eliminating ability of cells that cause a shift between oxidants and antioxidants in favor of oxidants, and result in chronic inflammation, apoptosis In the PBDE-209 treated groups, up-regulations of AwSOD and AwCAT expression exhibited a time-and dose-dependent pattern.…”

Colonic and Hepatic Modulation by Lipoic Acid and/or N‐Acetylcysteine Supplementation in Mild Ulcerative Colitis Induced by Dextran Sodium Sulfate in Rats

“…Antioxidants-treated rats were supplemented 7 days before mild colitis induction with lipoic acid (LA, 100 mg/kg/d), N-acetylcysteine (NAC, 100 mg/kg/d), or LA + NAC (100 mg/kg/d, each). Doses of the two antioxidants used are considered safe to rats/mice (LA up to 1800 mg/d [17] and NAC up to 6000 mg/d) and have been tested successfully in several physiological/pathophysiological conditions in mice/rats [16, 18]. …”

“…However, the most important antioxidant action assigned to NAC is the increase in antioxidant defense activity by providing cysteine, which is required for GSH synthesis. The anti-inflammatory effects of NAC have also been confirmed, through observation of NF-kB inhibition [16]. …”