Determination of DNA Damage in Experimental Liver Intoxication and Role of N-Acetyl Cysteine

Abstract

The present study aimed at detecting DNA damage and fragmentation as well as histone acetylation depending on oxidative stress caused by CCl4 intoxication. Also, the protective role of N-acetyl cysteine, a precursor for GSH, in DNA damage is investigated. Sixty rats were used in this study. In order to induce liver toxicity, CCl4 in was dissolved in olive oil (1/1) and injected intraperitoneally as a single dose (2 ml/kg). N-acetyl cysteine application (intraperitoneal, 50 mg/kg/day) was started 3 days prior to CCl4 injection and continued during the experimental period. Control groups were given olive oil and N-acetyl cysteine. After 6 and 72 h of CCl4 injection, blood and liver tissue were taken under ether anesthesia. Nuclear extracts were prepared from liver. Changes in serum AST and ALT activities as well as MDA, TAS, and TOS levels showed that CCl4 caused lipid peroxidation and liver damage. However, lipid peroxidation and liver damage were reduced in the N-acetyl cysteine group. Increased levels in 8-hydroxy-2-deoxy guanosine and histone acetyltransferase activities, decreased histone deacetylase activities, and DNA breakage detected in nuclear extracts showed that CCl4 intoxication induces oxidative stress and apoptosis in rat liver. The results of the present study indicate that N-acetyl cysteine has a protective effect on CCl4-induced DNA damage.

Nutri-Protection and Mediterranean Diet: Bitter Apricot Kernel and Amygdalin Treatment Effects on a Battery of Oxidative Stress and Apoptosis Biomarkers

“…Increased levels in 8-hydroxy-2-deoxy guanosine and histone acetyltransferase activities, decreased histone deacetylase activities, and DNA breakage detected in nuclear extracts showed that CCl 4 intoxication induces oxidative stress and apoptosis in rat liver. The results of their study indicate that N-acetyl cysteine has a protective effect on CCl 4 -induced DNA damage [20].In addition of these TAS levels of 5% BAK and CCl 4 group higher than control as very important situation for and mild hepatic necrosis and rarely intracellular vacuolization and vascular congestion (Figures 6A and 6B). …”

“…Therefore, it was demonstrated that rutin attenuated BDL-induced hepatic inflammation [23]. Liver fibrosis was induced in a mouse model using CCL 4 (intraperitoneal injection, three times a week for 8 weeks), and astaxanthin was administered everyday at three doses (20,40, and 80 mg/kg). Their pathologically results showed that astaxanthin significantly improved the pathological lesions of liver fibrosis.…”

“…The ratio of TOS to TAS was accepted as the OSI. For the calculation, the resulting unit of TAS was converted to μmol/gr protein, and the OSI value was calculated according to the following formula: OSI (arbitrary unit) = TOS (mmol H 2 O 2 equivalent/L)/TAS (mmol Trolox equivalent/L) [20].…”

Resveratrol attenuates hepatic complications associated with insulin resistance: Implications on hepatic HAIR, LAIR, cell energy and DNA fragmentation

“…Oxidative and nitrosative stresses causing structural and functional alterations in the cellular biomolecules and cell membrane are the result of the development of complications in diabetic individuals (D'Archivio et al, 2012, Fisher-Wellman,Bloomer, 2009, Park et al, 2009. Attack by ROS and RNS leads to DNA hydroxylation; oxidizing DNA to form 8-hydroxy-2-deoxyguanosine (8-OHDG) adducts; a major species of oxidative DNA damage (Aksit,Bildik, 2014). 8-OHDG content is considered a sensitive biomarker of the oxidative DNA damage and repair (Abdelali et al, 2016).…”

Ameliorative effects of N-acetylcysteine on fluoride-induced oxidative stress and DNA damage in male rats’ testis

“…Moreover, it could be seen that these antidotes exhibited the role of resisting fluorosis mainly through the mechanism of inhibiting oxidative stress and DNA damage. Some animal researches showed that NAC could prevent postischaemic reperfusion injury in hepatic tissue, CCl4 -induced liver damage and brain intoxication induced by propionic acid (PPA) by reducing DNA damage and oxidative stress [46][47][48]. Moreover recent human studies implied that NAC could attenuate pesticide-induced DNA damage in human peripheral blood mononuclear cells, and age-related increases in genetic damage in human T lymphocytes, in vitro and ex vivo [49,50].…”