Effects of nitrosyl ruthenium in injury brain induced by ischemia and reperfusion of rats

Abstract

IntroduÃÃo e objetivo: Doadores de NO podem diminuir a lesÃo neuronal durante a isquemia e reperfusÃo cerebral (I/R) por aumento do fluxo sanguÃneo cerebral. O objetivo deste estudo à avaliar se um novo complexo de nitrosilo complexo de rutÃnio (Rut-bpy) capaz liberar NO direto na musculatura lisa vascular apresenta algum efeito durante I/R. MÃtodo: Foram utilizados 96 ratos machos, da linhagem Wistar, com peso mÃdio de 290.27 g, distribuÃdos em 2 fases com 8 grupos cada: Fase de isquemia 4 grupos sham (SF, Rut-bpy,L-NAME e L-NAME+Rut-bpy) e 4 grupos isquemia (SF, Rut-bpy,L-NAME e L-NAME+Rut-bpy); da mesma forma foi dividido a fase de reperfusÃo ( 4 grupos sham e 4 grupos isquemia/reperfusÃo) com as mesmas drogas teste da fase de isquemia. Foi utilizado um modelo de isquemia cerebral global incompleta, com oclusÃo da artÃria carÃtida comum bilateral e administraÃÃo do SF, Rut-bpy e L-NAME via intraperitoneal. No final do experimento os animais foram decapitados e o cÃrebro fatiado para ser avaliado à Ãrea de lesÃo por histoquÃmica. Durante todo o experimento a PAM dos animais foi monitorizada. Resultados: DiminuiÃÃo da relaÃÃo Ãrea de lesÃo/Ãrea de tecido cerebral tanto na fase de isquemia (0.526 + 0.012 com SF vs 0.216 + 0.07 com Rut-bpy,; p<0.05) como na fase de reperfusÃo (0.4201 + 0.04 com SF vs 0.114 + 0.03 com Rut-bpy; p<0.05). A variaÃÃo da PAM foi menor nos animais tratados com Rut-bpy (20.89 + 11.77 com SF vs 6.49 + 4.65 com Rut-bpy) ao final da isquemia e inicio da reperfusÃo. ConclusÃo: O Rut-bpy tem efeito protetor neuronal durante evento de I/R e que o mesmo consegue manter a PAM mais estÃvel durante o inicio da reperfusÃo.Background and purpose - Nitric oxide (NO) donors are known to reduce neuronal damage during brain ischemia and reperfusion by increasing the blood flow. Rut-bpy is a novel nitrosyl-ruthenium complex releasing NO directly into the vascular smooth musculature. The objective of the study was to evaluate the effect of Rut-bpy on a rat model of brain ischemia and reperfusion. Methods - Ninety-six male Wistar rats weighing approximately 290g were randomly assigned to 16 groups. Four groups and their respective sham groups were submitted to ischemia (Stage 1), while four groups and their respective sham groups were submitted to ischemia + reperfusion (Stage 2). At each stage of the experiment the groups were treated pairwise with saline solution (SS), Rut-bpy, L-NAME and L-NAME+Rut-bpy, respectively. The study was based on an incomplete global brain ischemia model with occlusion of the common bilateral carotid arteries and intraperitoneal administration of the study drugs. Following the experiment the animals were decapitated and the brain was sectioned for histochemical evaluation of the area of damage. The mean arterial blood pressure (MABP) was monitored throughout the experiment. Results - In the groups receiving Rut-bpy the damaged area/total area ratio decreased significantly during both ischemia (SS: 0.526  0.012 vs. Rut-bpy: 0.216  0.07; p<0.05) and reperfusion (SS: 0.4201  0.04 vs. Rut-bpy: 0.114  0.03; p<0.05). MABP oscillated significantly less during the transition from ischemia to reperfusion in the groups treated with Rut-bpy (SS: 20.89 mmHg  11.77 vs. Rut-bpy: 6.49 mmHg  4.65; p<0.05). Conclusion - Rut-bpy was shown to protect rat brain cells during ischemia and reperfusion and helped maintain the blood pressure relatively stable during the transition from ischemia to reperfusion

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