The effects of erdosteine, N‐acetylcysteine and vitamin E on nicotine‐induced apoptosis of cardiac cells

Abstract

This study was conducted to investigate the frequency of apoptosis in rat cardiomyocytes after intratraperitoneal nicotine injection, in order to examine the roles of inflammatory markers [myeloperoxidase (MPO) and tumor necrosis factor alpha (TNF-alpha)] in nicotine-induced cardiac damage and to determine the protective effects of three known antioxidant agents (N-acetylcysteine (NAC), erdosteine and vitamin E) on nicotine toxicity in the heart. Female Wistar rats were divided into seven groups, each composed of nine rats: two negative control groups, two positive control groups, one erdosteine-treated group (500 mg kg(-1)), one NAC-treated group (500 mg kg(-1)) and one vitamin E-treated group (500 mg kg(-1)). Nicotine was intraperitoneally injected at a dosage of 0.6 mg kg(-1) for 21 days. Following nicotine injection, the antioxidants were administered orally; treatment was continued until the rats were killed. Heart tissue samples were stained with hematoxylin-eosin for histopathological assessments. Apoptosis level in cardiomyocytes was determined by using TUNEL (terminal deoxynucleotidyl transferase-mediated dUTP nick endlabelling) method. Staining of cytoplasmic TNF-alpha in cardiomyocytes and heart MPO activity were evaluated by immunohistochemistry. The treatments with erdosteine, NAC and vitamin E significantly reduced the rate of nicotine-induced cardiomyocyte apoptosis. The effect of vitamin E on apoptosis regulation was weaker than the effects of erdosteine and NAC. Erdosteine, NAC and vitamin E significantly reduced the increases in the local production of TNF-alpha and heart MPO activity. This findings suggest that the effects of erdosteine and NAC on apoptosis regulation are stronger than that of vitamin E.

Angiotensin II Type I Receptor Antagonism Attenuates Nicotine-Induced Cardiac Remodeling, Dysfunction, and Aggravation of Myocardial Ischemia-Reperfusion Injury in Rats

“…Several lines of evidence have now reported that nicotine has pro-inflammatory actions in the cardiovascular system. In rats, nicotine administration for 21 days caused significant up-regulation of TNFα and myeloperoxidase accumulation in heart tissues (Demiralay et al, 2007). Nicotine also increased gene expression of TNFα and inducible nitric oxide synthase in mouse peritoneal macrophages and RAW264.6 macrophages in vitro (Lau et al, 2006).…”

“…Oxidative stress has been broadly implicated as a major cause of nicotine-induced cardiovascular abnormalities both in vivo and in vitro. Indeed, supplementation with exogenous antioxidants such as vitamin E orally as well as through metallothionein overexpression; effectively prevented nicotine-induced cardiac damage in these animal models (Demiralay et al, 2007;Erat et al, 2007;Gumustekin et al, 2010;Hu et al, 2011). Although it is suggested that nicotine-induced upregulation of reactive oxygen species (ROS) production drives cardiac hypertrophy, fibrosis, and inflammation upon chronic exposure (Hu et al, 2011;Ramalingam et al, 2016), limited data is available to describe precise mechanisms underlying nicotine-induced oxidative stress and cardiac dysfunction in vivo.…”

Prenatal Nicotine Increases Matrix Metalloproteinase 2 (MMP-2) Expression in Fetal Guinea Pig Hearts

“…To test the effect of oxidative stress on fetal hearts, N-acetylcysteine (NAC; 10 mg/mL, N ¼ 4) was administered in the drinking water in the presence/absence of nicotine at a dose (496 + 37 mg/kg per d) that was effective (300-500 mg/kg) in inhibiting oxidative stress. [30][31][32] N-Acetylcysteine is an endogenous substrate in glutathione synthesis, a natural antioxidant via the glutathione pathway, 33 and considered safe during pregnancy. 34 At near term, pregnant animals were anesthetized with ketamine (80 mg/kg) and xylazine (1 mg/kg) and administered a subcutaneous injection of lidocaine prior to receiving an abdominal incision.…”

Effect of montelukast on spinal cord ischemia/reperfusion injury

“…The incubation process was continued by incubation with primary anti-MPO antibody, biotinylated goat-mouse antibody and chromogenic substrate. Following this process, the sections were counterstained with hemotoxylin-eosin (8). The ration of the stained MPO in the cytoplasm of the neutrophils was evaluated by means of intensity and frequency of staining (26).…”