Reactive oxygen and nitrogen species modulate the ex-vivo effects of LPS on platelet adhesion to fibrinogen

LIFE SCIENCES

卷:89

Article

Casarin, Andre Luis¹  Lopes-Pires, Maria Elisa¹  Morganti, Rafael Prada¹  Antunes, Edson¹  Marcondes, Sisi¹ 

[1] Univ Estadual Campinas, UNICAMP, Dept Pharmacol, Fac Med Sci, BR-13084971 Campinas, SP, Brazil

关键词: Platelet adhesion;    Lipopolysaccharide;    Nitric oxide;    Oxidative stress;   

DOI  :  10.1016/j.lfs.2011.09.004

来源: Elsevier

【 摘 要 】

Aims: Excessive production of nitric oxide (NO) and reactive oxygen species (ROS) in sepsis modulates different cell functions. Since the sepsis severity is associated with the degree of platelet activation, we decided to investigate the role of systemic generation of NO and ROS in modulating the platelet adhesion of lipopolysaccharide (LPS)-treated rats. Main methods: Platelet adhesion was evaluated using fibrinogen-coated 96-well microtiter plates. Cyclic GMP levels were measured using enzyme immunoassay kit. Key findings: Treatment of rats with LPS significantly increased spontaneous platelet adhesion, but reduced the thrombin-activated platelet adhesion when compared with control rats. Chronic treatment of rats with the NO synthase inhibitor L-NAME (20 mg/rat/day, 7 days) prior to LPS injection normalized the increased adhesion in non-activated platelets, but failed to affect the adhesion in thrombin-activated platelets. The cGMP levels were modified neither in non-activated nor in thrombin-activated platelets of LPS-treated rats when compared with control rats. The incubation of non-activated platelets with the O-2(-) scavenger PEG-SOD reversed the stimulatory effect of LPS on spontaneous adhesion, but had no effect in stimulated-platelet adhesion of non-treated or LPS-treated groups. Moreover, pretreatment of rats with the antioxidant N-acetylcysteine (NAC: 150 mg/kg) prevented the increase of non-activated platelet adhesion, and significantly reduced the inhibitory effect of LPS on thrombin-stimulated adhesion. Significance: Our findings suggest that in LPS-treated rats, NO plays an important modulatory role only in non-stimulated platelet adhesion through cGMP-independent mechanisms, while ROS, directly or by affecting the redox state of the animals, modulates both non-activated and thrombin-activated platelet adhesion. (C) 2011 Elsevier Inc. All rights reserved.

【 授权许可】

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