Protective Effects of Zinc, Pentoxifylline, and N-Acetylcysteine in an Animal Model of Laparoscopy-Induced Ischemia/Reperfusion Injury of the Small Intestine

Abstract

Pneumoperitoneum induced to facilitate laparoscopy is associated with splanchnic hypoperfusion, ischemia/reperfusion (I/R) injury, and oxidative stress. This study investigated the effects of pre- and postlaparoscopic conditioning, zinc, pentoxifylline, and N-acetylcysteine on markers of I/R injury of the small intestine in an animal model. Male Sprague-Dawley rats (n=56) were randomized to 1 of 7 treatment groups. Except for group 7 (control group that underwent sham surgery without pneumoperitoneum), pneumoperitoneum was induced in all by use of carbondioxide insufflation under a pressure of 15 mmHg. Group 1 (laparoscopic I/R) was subjected to 60 minutes of pneumoperitoneum. Group 2 (laparoscopic preconditioning plus laparoscopy) was subjected to 5 minutes of insufflation and 5 minutes of desufflation followed by 60 minutes of pneumoperitoneum. Group 3 (laparoscopy plus laparoscopic postconditioning) was subjected to 60 minutes of pneumoperitoneum and 60 minutes of desufflation followed by 5 minutes of insufflation and 5 minutes of desufflation. Group 4 (zinc), group 5 (pentoxifylline), and group 6 (N-acetylcysteine) received a single intraperitoneal injection of zinc (50 mg/kg), pentoxifylline (50 mg/kg), or N-acetylcysteine (150 mg/kg), respectively, 5 minutes before the desufflation period. Animals were killed at the end of the experiments, and small intestine samples were tested for malondialdehyde (MDA), catalase (CAT), glutathione peroxidase (GPX), and superoxide dismutase (SOD). There was no significant difference for MDA levels between each other in the groups 1, 2, and 3. But MDA levels were higher significantly in groups 1, 2, and 3 than those of groups 4, 5, 6, and 7. SOD and GPX levels of group 3 were significantly higher than those of groups 1, 2, 4 through 7. According to the SOD levels, there was no significant difference between each other in those of groups 1, 2, 4 through 7. GPX levels of group 3 were significantly higher than those of groups 1, 2, 4 through 7. GPX levels of group 1 were significantly lower than those of groups 5 and 7. The mean CAT level of groups 1 and 2 was significantly lower than that of groups 3, 6, and 7. The mean CAT level of group 3 was significantly higher than that of groups 1, 2, 4 through 7. In this animal model of small intestine I/R injury, laparoscopy caused small intestine ischemia as evidenced by elevated markers of tissue I/R injury. This effect was significantly attenuated by zinc, pentoxifylline, and N-acetylcysteine, but not by prelaparoscopy conditioning and postlaparoscopy conditioning.