Beneficial effects of melatonin on nicotine-induced vasculopathy

Abstract

Tobacco smoking is responsible for death of many people each year and increases the risk of developing numerous disorders, particularly cardiovascular disease and cancer. Among the components of cigarette smoke, nicotine is known to excert proatherosclerotic, prothrombotic and proangiogenic effects on vascular endothelial cells. The current study was designed to investigate the mechanisms by which nicotine induces endothelial dysfunction and further to examine whether melatonin protects against nicotine-induced vasculopathy. Four groups of male rats (controls, melatonin-treated, nicotine treated [100 microg/mL in drinking water], and nicotine plus melatonin [5 mg/kg/day] treated) were used in this study. After 28 days all the animals were killed by decapitation and the aorta was removed. We evaluated the hydroxyproline content, and the different expression of proteins involved in several types of stress (ERK1/2), in fibrosis (TGF-beta1, NF-kappaB) and in recruitment of circulating leukocytes onto the vessel wall, including intercellular adhesion molecule-1 (ICAM-1) and vascular cellular adhesion molecule-1 (VCAM-1). These metabolic pathways are important in the development of nicotine-induced atherosclerosis and hypertension. Our results show that nicotine induces marked structural and functional alterations in the aorta. Nicotine receptor binding results in activation and phosphorylation of ERK 1/2. This enzyme, in turn, activates both TGF-beta1 and NF-kappaB; they stimulate respectively the synthesis of type I collagen, responsible of fibrosis, and moreover ICAM-1, VCAM-1 and reactive oxygen species. Based on these findings, melatonin is able to minimize the negative effects of nicotine by blocking the activation of ERK and the other signalling pathways in which this enzyme is involved.

Agmatine Ameliorates Nicotine Induced Lung Injury in Rats through Decrease TGF-ß1 and Bax Immunoexpression and by Anti-oxidative Sress Pathway: Histological, Immunohistochemical and Biochemical Study

“…ICAM-1/VCAM-1 are principle modulators for the stable adhesion of leukocytes, including neutrophils and lymphocytes in alveolar epithelial cells [43]. Rodella et al [44] discovered marked elevation in VCAM-1 expression upon NIC treatment in vitro and in vivo respectively. Data of the existing study demonstrated that NIC treated animals had marked elevation in VCAM-1 activity.…”

The Effect of Circadian Melatonin Levels on Inflammation and Neurocognitive Functions Following Coronary Bypass Surgery

“…36,37) Melatonin was shown to block ICAM-1 release in a variety of studies that investigated its vascular effects. 37,38) Potential neurological and neuropsychological complications following cardiac surgery are categorised into two major groups. Type 1 complications (with an incidence of 3%-6%) include death due to stroke or hypoxic encephalopathy, non-fatal incident stroke, transient ischaemic attack, stupor and coma.…”

Endothelial dysfunction and melatonin

“…In other words, there had been preconditions typical of chronic nicotine intoxication, which lead to hypertension and atherosclerosis. A long-term (28 days) combined of МТ (5 mg/kg) along with nicotine, however, prevented the side effects of smoking [71].…”