Posted 14 April 2009 - 04:00 AM
NAC's disruption of redox signalling also impairs healing and eliminates a benefit of angiotensin receptor blockers.
Crit Care. 2009 Apr 9;13(2):R55.
Prolonged treatment with N-acetylcystine delays liver recovery from acetaminophen hepatotoxicity.
Yang R, Miki K, He X, Killeen ME, Fink MP.
ABSTRACT: INTRODUCTION: Acetaminophen (APAP) toxicity is the most common cause of acute liver failure in the US and Europe. Massive hepatocyte necrosis is the predominant feature of APAP-induced acute liver injury (ALI). Liver regeneration is a vital process for survival after a toxic insult, it occurs at a relative late time point after the injurious phase. Currently N-acetylcysteine (NAC), a glutathione precursor, is the antidote for acetaminophen overdose. However, NAC is effective only for patients who present within hours of an acute overdose, and is less effective for late-presenting patients. It is possible that in delayed patients, previously reduced endogenous glutathione (GSH) level has restored, prolonged treatment with NAC might be toxic and impairs liver regeneration. Therefore, we hypothesize that prolonged treatment with NAC impairs liver regeneration in ALI induced by APAP. METHODS: ALI was induced in C57BL/6 male mice by a single dose of APAP (350 mg/kg) intraperitoneal injection. Following 2 hrs of APAP challenge, the mice were given 100 mg/kg NAC dissolved in 0.6 mL saline, or saline treatment every 12 hours for a total of 72 hours. RESULTS: 72 hrs after APAP challenge, compared to saline treatment, NAC treatment significantly increased serum transaminases (ALT/AST), induced evident hepatocytes vacuolation in the periportal area and delayed liver regeneration seen in histopathology. This detrimental effect was associated with reduced hepatic NF-kappaB DNA binding and decreased expression of cell cycle protein cyclin D1, two important factors in liver regeneration. CONCLUSIONS: Prolonged treatment with NAC impairs liver regeneration in ALI induced by APAP.
PMID: 19358737
Kulak Burun Bogaz Ihtis Derg. 2007;17(1):22-5.
Does topical N-acetylcysteine application after myringotomy cause severe otorrhea?
Sanli A, Eken M, Evren C, Ateş G, Paksoy M.
Department of Otolaryngology, Dr. Lütfi Kirdar Training and Research Hospital, Istanbul, Turkey.
OBJECTIVES: The effect of topical N-acetylcysteine (NAC) application was investigated on the healing of acute experimental tympanic membrane perforations. MATERIALS AND METHODS: Twenty guinea pigs were used in this study. Under intraperitoneal ketamine anesthesia, incisional myringotomies were performed in the posterosuperior quadrant of the tympanic membranes with a straight otologic hook. The diameter of the perforations was approximately 2 mm. Perforations in both ears were treated with freshly prepared sponges soaked in either 0.1 ml 0.9% NaCl solution (10 control animals) or 0.6 mg/0.1 ml NAC (10 animals) for three consecutive days. All the tympanic membranes were examined by otomicroscopy on the third, fifth, seventh, and ninth days. RESULTS: In the control group, all the perforations were completely closed at the end of nine days. During the same period, only 40% of the perforations were completely closed in the NAC group. The remaining ears exhibited otorrhea by the third day. CONCLUSION: N-acetylcysteine may cause severe otorrhea in the healing process of tympanic membrane perforations. Further studies including histopathological examinations are required to elucidate this condition.
PMID: 17483607
Antioxid Redox Signal. 2008 Dec;10(12):1999-2008.
N-acetylcysteine abolishes the protective effect of losartan against left ventricular remodeling in cardiomyopathy hamster.
Matsuhisa S, Otani H, Okazaki T, Yamashita K, Akita Y, Sato D, Moriguchi A, Iwasaka T.
The Second Department of Internal Medicine, Division of Cardiology, Kansai Medical University, Moriguchi City, Japan.
Oxidative stress mediated by activation of angiotensin II type-1 receptor (AT(1)R) plays a crucial role in the progression of heart failure. We investigated the effect of N-acetylcysteine (NAC) and an AT(1)R blocker on oxidative stress and left ventricular (LV) remodeling in BIO14.6 cardiomyopathy hamsters. The cardiomyopathy hamsters were treated with NAC or the AT(1)R blocker losartan for 20 weeks. Although NAC and losartan inhibited oxidative stress and upregulation of iNOS in the cardiomyopathy hamster heart, only losartan inhibited LV chamber dilation, myocardial fibrosis, and LV dysfunction in the cardiomyopathy hamster. Co-treatment with NAC abolished the protective effect of losartan against LV remodeling associated with inhibition of phosphatidylinositol 3-kinase (PI3K)/Akt and eNOS activation. An iNOS inhibitor 1400W or a nonselective NOS inhibitor Nomega-nitro-L-arginine methyl ester (L-NAME) exacerbated LV remodeling in the cardiomyopathy hamster. However, L-NAME but not 1400W abrogated losartan-mediated inhibition of LV remodeling. These results suggest that redox-sensitive upregulation of iNOS plays a crucial role in preventing LV remodeling in the BIO14.6 cardiomyopathy hamster. Losartan inhibits LV remodeling by switching the cardioprotective mechanism from iNOS- to eNOS-dependence, but NAC abolishes the protective effect of losartan by inhibiting redox-sensitive activation of PI3K/Akt and eNOS in the cardiomyopathy hamster.
PMID: 18665799