N-Acetyl Cysteine (NAC)

N-acetylcysteine ameliorates nitrosative stress on radiation-inducible damage in rat liver.
Kilciksiz S, Demirel C, Evirgen Ayhan S, Erdal N, Gurgul S, Tamer L, Ayaz L.
J BUON. 2011 Jan-Mar;16(1):154-9.

 The present study was designed to investigate the potential radioprotective effects of N-acetylcysteine (NAC) on radiation-induced nitrosative stress caused by gamma irradiation (single dose, 6 Gy) in rat liver. The rats (n=40) were divided randomly and equally into 4 groups: Control (C), Radiation (R), R+NAC (received irradiation and 1,000 mg/kg of NAC) and R+WR-2721 (received irradiation and 200 mg/kg of WR-2721). Liver tissue of each animal was harvested and utilized for 3-nitrotyrosine (3-NT) detection using high-performance liquid chromatography- ultraviolet (HPLC-UV) system. In the R rats, 3-NT levels significantly increased when compared to those of the C rats (p<0.05). There were no significant differences in the 3-NT levels among R+NAC and R+WR-2721 rats. Histologically examined liver tissue samples showed no obvious differences. The present study suggests that irradiation has a negative effect on the cellular proteins by enhancing 3-NT formation. The prophylactic use of NAC seems to reduce the nitrosative damage during radiotherapy. PMID: 21674868

Antioxidant Therapy Attenuates Deficient Bone Fracture Repair Associated With Binge Alcohol Exposure.
Volkmer DL, Sears B, Lauing KL, Nauer RK, Roper PM, Yong S, Stover M, Callaci JJ.
J Orthop Trauma. 2011 Jul 6.

 Alcohol consumption is a known risk factor for traumatic injuries of all types and has been shown to produce detrimental effects on bone metabolism. Although the mechanisms responsible for these detrimental effects are not well characterized, oxidative stress from alcohol exposure appears to play a central role. This study was designed to examine the effect of a short-term binge alcohol consumption pattern on fracture repair and the effect of an antioxidant, N-acetylcysteine, on fracture healing after binge alcohol consumption. One hundred forty-four adult male Sprague-Dawley rats underwent unilateral closed femur fracture after injection of either saline or alcohol to simulate a binge alcohol cycle. Animals in the antioxidant treatment group received daily N-acetylcysteine after fracture. Femurs were harvested at 1, 2, 4, and 6 weeks after injury and underwent biomechanical testing and histologic analysis. Binge alcohol administration was associated with significant decreases in biomechanical strength at 1- and 2-week time points with a trend toward decreased strength at 4- and 6-week time points as well. Alcohol-treated animals had less cartilage component within the fracture callus and healed primarily by intramembranous ossification. Administration of N-acetylcysteine in alcohol-treated animals improved biomechanical strength to levels comparable to the control animals and was associated with increased endochondral ossification. Our results indicate that binge alcohol alters the quality of fracture healing after a traumatic injury and that concurrent administration of an antioxidant is able to reverse these effects. PMID: 21738068

  Experimental and clinical evidence for modification of hepatic ischaemia-reperfusion injury by N-acetylcysteine during major liver surgery.
Jegatheeswaran S, Siriwardena AK.
HPB (Oxford). 2011 Feb;13(2):71-8.

 Hepatic ischaemia-reperfusion (I/R) injury occurs in both liver resectional surgery and in transplantation. The biochemistry of I/R injury involves short-lived oxygen free radicals. N-acetylcysteine (NAC) is a thiol-containing synthetic compound used in the treatment of acetaminophen toxicity. The present study is a detailed overview of the experimental and clinical evidence for the use of NAC as a pharmaco-protection agent in patients undergoing major liver surgery or transplantation. A computerized search of the Medline, Embase and SCI databases for the period from 1st January 1988 to 31st December 2008 produced 40 reports. For clinical studies, the quality of reports was assessed according to the criteria reported by the Cochrane communication review group. Nineteen studies evaluated NAC in experimental liver I/R injury. NAC was administered before induction of ischaemia in 13. The most widely used concentration was 150 mg/kg by intravenous bolus. Fifteen studies report an improvement in outcome, predominantly a reduction in transaminase. Seven studies used an isolated perfused liver model with all showing improvement (predominantly an improvement in bile production after N-acetylcysteine). Two out of four transplantation models showed an improvement in hepatic function. Clinical studies in transplantation show a modest improvement in transaminase levels with no beneficial effect on either patient or graft survival. N-acetylcysteine, given before induction of a liver I/R injury in an experimental model can ameliorate liver injury. Clinical outcome data are limited and there is currently little evidence to justify use either in liver transplantation or in liver resectional surgery. PMID: 21241423
Copyright © 2011 International Hepato-Pancreato-Biliary Association

  Treatment of ricin A-chain-induced hepatotoxicity with liposome-encapsulated N-acetylcysteine.
Buonocore C, Alipour M, Omri A, Pucaj K, Smith MG, Suntres ZE.
J Drug Target. 2011 May 26.

 The toxicity of ricin resides in the ricin A-chain (RTA) and is attributed to the inhibition of protein synthesis but inflammation and oxidative stress have also been implicated. RTA can independently enter cells producing comparable tissue injury and inflammation, although at much higher concentrations than intact ricin. Treatment for exposure to ricin or RTA is supportive. Purpose: To examine the effectiveness of conventional or liposome-encapsulated N-acetylcysteine (Lipo-NAC) in ameliorating RTA-induced hepatotoxicity. Methods: Four hours after RTA administration (90 µg/kg b.wt, iv), rats were treated with conventional NAC or Lipo-NAC (25 mg/kg NAC). The hepatoprotective effects of the antioxidant formulations were assessed by measuring indexes for liver injury (alanine [ALT] and aspartate [AST] aminotransferase activities), inflammation (myeloperoxidase, tumor necrosis factor-α, chloramine levels), and oxidant response (lipid peroxidation, nitrotyrosine, glutathione levels) 24-h post-RTA exposure. Results: Administration of RTA to animals resulted in hepatotoxicity as demonstrated by elevated plasma ALT and AST levels, increases in an inflammatory response, and increases in oxidant response. Treatment of animals with the antioxidant formulations reversed the RTA-induced hepatotoxicity, being most evident following the administration of Lipo-NAC. Conclusion: NAC, administered in a liposomal form, may serve as a potentially effective pharmacological agent in the treatment of RTA-induced liver injuries. PMID: 21615215