title: Water-Pipe Smoke Exposure-Induced Circulatory Disturbances in Mice, and the Influence of Betaine Supplementation Thereon.
abstract: OBJECTIVE
  It has been shown, both experimentally and clinically, that water-pipe smoke (WPS) exposure adversely affects the cardiovascular system (CVS) through the generation of oxidative stress and inflammation. Betaine, a naturally occurring compound in common foods, has antioxidant and anti-inflammatory actions. However, its potential to mitigate the adverse effect of WPS on the CVS has never been reported before. This is the subject of this study in mice.
  
  
  METHODS
  Mice were exposed daily for 30 min to either normal air (control), or to WPS for two consecutive weeks. Betaine was administered daily by gavage at a dose of 10mg/kg, 1h before either air or WPS exposure.
  
  
  RESULTS
  Betaine mitigated the in vivo prothrombotic effect of WPS in pial arterioles and venules. Moreover, it reversed the WPS-induced decrease in circulating platelets. Likewise, betaine alleviated platelet aggregation in vitro, and the shortening of activated partial thromboplastin time and prothrombin time induced by WPS. Betaine reduced the increase of plasminogen activator inhibitor-1 and fibrinogen concentrations in plasma induced by WPS. Betaine also diminished the WPS-induced increase of plasma concentrations of interleukin 6 and tumor necrosis factor α, and attenuated the increase of lipid peroxidation and superoxide dismutase. Immunohistochemical analysis of the heart revealed an increase in the expression of inducible nitric oxide synthase and cytochrome C by cardiomyocytes of the WPS-exposed mice. These effects were averted by betaine.
  
  
  CONCLUSIONS
  Our findings suggest that betaine treatment significantly mitigated WPS-induced hypercoagulability, and inflammation, as well as systemic and cardiac oxidative stress.
authors.forename: Abderrahim
authors.initials: A
authors.lastname: Nemmar
authors.forename: Suhail
authors.initials: S
authors.lastname: Al-Salam
authors.forename: Sumaya
authors.initials: S
authors.lastname: Beegam
authors.forename: Priya
authors.initials: P
authors.lastname: Yuvaraju
authors.forename: Abderrahim
authors.initials: A
authors.lastname: Oulhaj
authors.forename: Badreldin H
authors.initials: BH
authors.lastname: Ali
mesh_terms: D000284:Administration, Oral; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D001622:Betaine / Q000494:pharmacology*; D001792:Blood Platelets / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D045304:Cytochromes c / Q000235:genetics / Q000378:metabolism; D005340:Fibrinogen / Q000235:genetics / Q000378:metabolism; D015870:Gene Expression / Q000187:drug effects; D015850:Interleukin-6 / Q000235:genetics / Q000378:metabolism; D015227:Lipid Peroxidation / Q000187:drug effects; D051379:Mice; D008810:Mice, Inbred C57BL; D032383:Myocytes, Cardiac / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000235:genetics / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects; D010314:Partial Thromboplastin Time; D017395:Plasminogen Activator Inhibitor 1 / Q000235:genetics / Q000378:metabolism; D010974:Platelet Aggregation / Q000187:drug effects; D061251:Primary Cell Culture; D011517:Prothrombin Time; D012907:Smoking / Q000009:adverse effects*; D013482:Superoxide Dismutase / Q000235:genetics / Q000378:metabolism; D013921:Thrombocytopenia / Q000209:etiology / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D013927:Thrombosis / Q000209:etiology / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism
chemical_list: D000975:Antioxidants; D015850:Interleukin-6; D017395:Plasminogen Activator Inhibitor 1; D014409:Tumor Necrosis Factor-alpha; C577686:interleukin-6, mouse; D001622:Betaine; D005340:Fibrinogen; D045304:Cytochromes c; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse; D013482:Superoxide Dismutase
keywords: Betaine; Heart; Inflammation; Nose-only exposure; Oxidative stress; Thrombosis; Water-pipe smoke