Hyperbaric oxygen treatment and N-acetylcysteine ameliorate acetaminophen-induced liver injury in a rat model

Abstract

An overdose of acetaminophen (APAP) produces centrilobular hepatocellular necrosis. We aimed to investigate the hepatoprotective effects of N-acetylcysteine (NAC) only and hyperbaric oxygen (O(2)) treatment (HBOT) combined with NAC, and their anti-inflammatory properties in liver tissue. In the current study, a total of 32 male Sprague Dawley rats were divided into 4 groups: sham, APAP, NAC, and NAC + HBOT. In the APAP, NAC, and NAC + HBOT groups, liver injury was induced by oral administration of 1 g/kg APAP. The NAC group received 100 mg/kg NAC per day. NAC + HBOT group received intraperitoneal injection of 100 mg/kg/day NAC and were given HBOT at 2.8 ATA pressure with 100% O(2) inhalation for 90 min every 12 h for 5 days. Rats in the sham group received distilled water only by gastric tube. All animals were killed on day 6 after APAP or distilled water administration. Serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) activities, hepatic neopterin, tumor necrosis factor-α (TNF-α), and interleukin 6 (IL-6) levels were measured. There was a significant increase in serum AST and ALT activities in the APAP group compared with the sham group (in both p = 0.001). NAC and NAC + HBOT groups had significant decreases in hepatic neopterin, TNF-α, and IL-6 levels compared with the APAP group. APAP administration caused extensive hepatic necrosis. NAC and NAC + HBO treatments significantly reduced APAP-induced liver injury. Our results showed that the liver damage in APAP toxicity was attenuated by NAC and NAC + HBO treatments. NAC + HBOT exhibit hepatoprotective activity against APAP-induced liver injury in rats.

Protective Effect of Curcumin versus N-acetylcystein on Acetaminophen Induced Hepatotoxicity in Adult Albino Rats

“…Similarly, curcumin significantly inhibited the rise in AST, ALT and ALP by (52.8%, 37.08% and 41.8%) as compared to the relative acetaminophen group values. The previous results are in accordance with the results of previous researchers who demonstrated that these increases in liver enzymes were reduced by the administration of curcumin [38] and N-acetylcysteine [39].…”

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

“…Drug toxicity can also induce an inflammatory response through the production of cytokines by KCs and neutrophils, such as TNF-α, IL-6, IL-1β, IL-1α, and IFN-γ that modulate intracellular events [ 162 ]. These cytokines sensitize hepatocytes to biochemical stress, or regulate the adaptive immune-mediated cell injury.…”

“…There are many studies reporting the roles of NAC in APAP-induced liver injury. According to the study of Taslipinar et al (2013) [ 162 ] ( Table 2 ) that evaluated the hepatoprotective effects of NAC in an overdose of APAP producing centrilobular hepatocellular necrosis in rats, it was observed that doses of 100 mg/kg/day, i.p. for 5 days, significantly reduced hepatic TNF-α and IL-6.…”

“…Based on these results, NAC has shown hepatoprotective effects. In the work of Acharya et al (2010) [ 162 ] ( Table 2 ), NAC increased hepatic and serum levels of GSH and GSH/GSSG ratio, and liver and serum activities of GR, GST, and decreased hepatic and serum levels of MDA. NAPQI is capable of decrease GSH/GSSG ratio through the oxidation of the thiol group of GSH, and can also lead to the formation of interstrand disulfide linkages, in protein cross-links and protein-GSH mixed disulfides by oxidizing Cys thiol groups in proteins.…”

Normalization of QRS Segment, Blood Pressure and Heartbeat in an Experimental Model of Amitriptyline Intoxication in Rats Following Hyperbaric Oxygenation Therapy

“…HBO therapy has been used for carbon monoxide (Tilney, 2011;Weaver et al, 2002) and other types of intoxication (Youngster et al, 2010;Taslipinar et al, 2013). However, the mechanism of the beneficial effect has not been established.…”