101. Serum cytotoxin and oxidant stress markers in N-acetylcysteine treated thioacetamide hepatotoxicity of rats
- Author
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Mithat Bozdayi, Eranil S, Yurdaydin C, Ozden Uzunalimoglu, Kubilay Cinar, Akbay A, and Hakan Bozkaya
- Subjects
Male ,Antioxidant ,040301 veterinary sciences ,Health, Toxicology and Mutagenesis ,medicine.medical_treatment ,Pharmacology ,Thioacetamide ,Toxicology ,medicine.disease_cause ,030226 pharmacology & pharmacy ,0403 veterinary science ,Acetylcysteine ,Superoxide dismutase ,Rats, Sprague-Dawley ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,medicine ,Animals ,chemistry.chemical_classification ,biology ,Cytotoxins ,Glutathione peroxidase ,Liver Diseases ,04 agricultural and veterinary sciences ,General Medicine ,Glutathione ,Free Radical Scavengers ,Malondialdehyde ,digestive system diseases ,Rats ,Disease Models, Animal ,Oxidative Stress ,chemistry ,Immunology ,biology.protein ,Chemical and Drug Induced Liver Injury ,Oxidative stress ,Biomarkers ,medicine.drug - Abstract
N-acetylcysteine (NAC) is a glutathione precursor used to treat several clinical conditions where intracellular oxidant-antioxidant balance is disturbed, among which, acetaminophen induced hepatotoxicity may be counted. In this study, administering thioacetamide (TAA) as a hepatotoxic agent, a rat model of hepatotoxicity has been established, to investigate some of the immune mediated basic oxidant-antioxidant homeostatic mechanisms involved, and potential serum markers for follow-up of disease and treatment. To do this, four experimental groups receiving saline/saline, saline/NAC, saline/TAA and NAC/TAA as intraperitoneal injections, have been formed. Rat serum tumor necrosis factor-alpha (TNF-alpha), Interleukin1-beta (IL1-beta), malondialdehyde (MDA) as a measure of final oxidant damage and the antioxidant enzymes superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) have been assayed. Hepatocellular damage has been measured via the biochemical estimates ALT, AST and LDH as well as histopathological grading. It was found that both TNF-alpha and IL1-beta were significantly elevated in saline/TAA receivers (P0.01) when compared to NAC/TAA receivers. Serum MDA was also increased in TAA receivers in addition to SOD (P0.05) and GSH-Px (P0.05). Serum nitrite levels have also been assayed to give an estimate of nitric oxide that is suggested as a counter-balancer of oxidant stress. NAC/saline receivers had the highest levels of nitrites in the serum (P0.05). Our results indicate that part of the hepatocellular injury to rat liver, induced by TAA is mediated by oxidative stress caused by the action of cytokines imparted by the enzymatic SOD and GSH-Px and non-enzymatic gaseous nitric oxide mechanisms causing an alleviation on administration of NAC. In addition, TNF-alpha, IL1-beta, MDA, SOD, GSH-Px and nitrites are potential candidates of serum indicators for monitorization of pathophysiological stage of liver disease.
- Published
- 1999