title: Thromboembolic injury and systemic toxicity induced by nicotine in mice.
abstract: Nicotine is involved in the pathogenesis of hematological and cardiopulmonary diseases. The understanding of the pathophysiological mechanisms underlying these undesirable effects is however unclear. Cigarette smoking, nicotine gums and patches are common sources for nicotine ingestion. We have investigated the nicotine's effect on cerebral microvessel thrombosis and systemic toxicity. Mice received either nicotine (1 mg/kg, i.p.) or saline (control), once a day for 21 days. Briefly, after bolus intravenous fluorescein injection, a photo insult of cerebral microvessel was done. The platelet aggregation in microvessels was video recorded and analyzed. In conjunction, the plasma levels of superoxide dismutase (SOD), lactate dehydrogenase (LDH), liver enzymes, creatinine and blood urea nitrogen (BUN); and histopathological studies were carried out. Our results revealed a significant prothrombotic effect following nicotine exposure. Significant decrease in SOD indicates the occurrence of oxidative stress involved in the tissue damages and increase in the LDH emphasize the systemic toxicity. Substantial rise in the liver aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels were observed. Lungs histology showed intra-vascular hemorrhagic infarction with necrosis, macrophage and neutrophils infiltration. Liver histology showed intravascular thrombosis and portal inflammation. We conclude that the sub-acute nicotine exposure causes an increase in thrombosis in cerebral microvessels and systemic, hepatic and pulmonary toxicity.
authors.affiliation: Department of Physiology, Faculty of Medicine, UAE University, Al Ain, United Arab Emirates. m.fahim@uaeu.ac.ae.
authors.forename: Mohamed A
authors.initials: MA
authors.lastname: Fahim
authors.forename: Abderrahim
authors.initials: A
authors.lastname: Nemmar
authors.forename: Suhail
authors.initials: S
authors.lastname: Al-Salam
authors.forename: Subramanian
authors.initials: S
authors.lastname: Dhanasekaran
authors.forename: Mohamed
authors.initials: M
authors.lastname: Shafiullah
authors.forename: Javed
authors.initials: J
authors.lastname: Yasin
authors.forename: Mohamed Y
authors.initials: MY
authors.lastname: Hassan
mesh_terms: D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D001219:Aspartate Aminotransferases / Q000097:blood; D001806:Blood Urea Nitrogen; D002560:Cerebrovascular Circulation / Q000187:drug effects; D003404:Creatinine / Q000378:metabolism; D019793:Fluorescein / Q000737:chemistry; D005731:Ganglionic Stimulants / Q000633:toxicity; D007249:Inflammation; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008099:Liver / Q000201:enzymology; D008264:Macrophages / Q000378:metabolism; D008297:Male; D051379:Mice; D008833:Microcirculation / Q000187:drug effects; D009336:Necrosis; D009538:Nicotine / Q000633:toxicity*; D018384:Oxidative Stress; D012907:Smoking / Q000009:adverse effects; D013482:Superoxide Dismutase / Q000378:metabolism; D013923:Thromboembolism / Q000139:chemically induced*; D013927:Thrombosis / Q000139:chemically induced; D005723:gamma-Glutamyltransferase / Q000097:blood
chemical_list: D005731:Ganglionic Stimulants; D009538:Nicotine; D003404:Creatinine; D007770:L-Lactate Dehydrogenase; D013482:Superoxide Dismutase; D005723:gamma-Glutamyltransferase; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D019793:Fluorescein