N-acetylcysteine and meso-2,3-dimercaptosuccinic acid alleviate oxidative stress and hepatic dysfunction induced by sodium arsenite in male rats

• Published in: Drug design, development and therapy development and therapy, 2016-01, Vol.10, p.3425-3434
• Main Authors: Abu El-Saad, Ahmed M, Al-Kahtani, Mohammed A, Abdel-Moneim, Ashraf M
• Format: Article
• Language: English
• Subjects: 3-dimercaptosuccinic acid; Acetylcysteine; Acetylcysteine - administration & dosage; Acetylcysteine - pharmacology; Acetylcysteine - therapeutic use; Acids; Alanine; Alanine transaminase; Albinism; Animals; Antioxidants; Arsenic; Arsenic compounds; Arsenite; Arsenites - administration & dosage; Arsenites - toxicity; Aspartate aminotransferase; Bilirubin; Biology; Body weight; Care and treatment; Catalase; Chelation; Chemical and Drug Induced Liver Injury - drug therapy; Chemical and Drug Induced Liver Injury - metabolism; Chemical and Drug Induced Liver Injury - physiopathology; Combined treatment; Data recovery; Dimercaptosuccinic acid; Drinking water; Glutathione; Glutathione reductase; Health aspects; Laboratory animals; Levels; Lipid peroxidation; Lipids; Liver; liver pathology; Male; Malondialdehyde; meso-2; Metals; N-acetylcysteine; Original Research; oxidative imbalance; Oxidative stress; Oxidative Stress - drug effects; Poisoning; Rats; Rats, Wistar; Rodents; Selenium; Sodium; Sodium arsenite; Sodium Compounds - administration & dosage; Sodium Compounds - toxicity; Succimer - administration & dosage; Succimer - pharmacology; Succimer - therapeutic use; Toxicity; Vitamin E
• ISSN: 1177-8881; 1177-8881
• DOI: 10.2147/DDDT.S115339

Environmental exposure to arsenic represents a serious challenge to humans and other animals. The aim of the present study was to test the protective effect of antioxidant N-acetylcysteine (NAC) either individually or in combination with a chelating agent, meso-2,3-dimercaptosuccinic acid (DMSA), against sodium arsenite oral toxicity in male rats. Five groups were used: control; arsenic group (orally administrated in a concentration of 2 mg/kg body weight [b.w.]); the other three groups were orally administrated sodium arsenite in a concentration of 2 mg/kg b.w. followed by either NAC (10 mg/kg b.w., intraperitoneally [i.p.]), DMSA (50 mg/kg b.w., i.p.) or NAC plus DMSA. Arsenic toxicity caused significant rise in serum aspartate aminotransferase, alanine aminotransferase and total bilirubin, and a significant decrease in total protein (TP) and albumin levels after 3 weeks of experimental period. In addition, arsenic-treated rats showed significantly higher arsenic content in liver and significant rise in hepatic malondialdehyde level. By contrast, sharp decreases in glutathione content and catalase and glutathione reductase activities were discernible. NAC and/or DMSA counteracted most of these physiologic and biochemical defects. NAC monotherapy was more effective than DMSA in increasing TP, while DMSA was more effective in decreasing alanine aminotransferase. The combined treatment was superior over monotherapies in recovery of TP and glutathione. Biochemical data were well supported by histopathological and ultrastructural findings. In conclusion, the combination therapy of NAC and DMSA may be an ideal choice against oxidative insult induced by arsenic poisoning.