Effects of PARP Inhibitör 3-Aminobenzamide on Impaired Mesenteric Blood Flow and Organ Injury in CLP-Induced Septic Shock Model

Objective: In various pathophysiological conditions, including septic shock, reactive oxidants cause DNA strand breakage and subsequent activation of the nuclear enzyme poly (ADP ribose) polymerase (PARP). Activation of PARP results in cellular dysfunction. We investigated the 3-Aminobenzamide (3-AB), one of the pure PARP-1 inhibitor, on mesenteric blood flow and organ injury (lung, liver, spleen) in a murine caecal ligation and puncture (CLP) model of septic shock in both gender. Methods: Female and male Swiss albino mice received 3-AB (10 mg/kg, i.p.) or its solvent saline (0.9% NaCl, w/v) 1 hour after CLP. At 24th hour, the animals were anaesthetized with chloralhydrate (400 mg kg-1, i.p.) and the mesenteric blood flow was monitored for 15 min by using perivascular ultrasonic Doppler-flowmeter. Then the animals were exsanguinated, spleen, liver, and kidneys were isolated accordingly for histopathological examination. Thiobarbituric acid-reacting substances, glutathione and myeloperoxides activities were also determined in tissues. Results: Although the glutathione levels were decreased and thiobarbituric acid-reacting substances and myeloperoxidase activity were increased by CLP in lung and liver, 3-AB has failed to block these biochemical parameters. In CLP + saline group, the mesenteric arterial blood flow was significantly lower than that of saline group (p<0.0001). 3-AB administration, did not prevent this status. 3-AB also did not attenuate the histopathological injury inflicted by CLP. Conclusion: Poly (ADP-ribose) polymerase-1 inhibitor 3-AB, controversial to the common results of the recent literature, has no significant effect on splanchnic ischemia or multiple organ injury as histopathogically or biochemically in both gender.