Comparison of the effects of different doses of amantadine on lung tissue in lower extremity ischemia reperfusion injuries in rats

AIM: Ischemia/reperfusion (I/R) injury is a common complication after abdominal aortic surgery. In the literature, protective effects of N-Methyl D-Aspartate (NMDA) antagonists against ischemia/reperfusion injury in various tissues and organs have been shown. In our study, we aimed to investigate the effect of different doses of amantadine, an NMDA antagonist, on lung tissue after lower extremity I/R injury in rats. ETHOD: After approval of the ethics committee, 36 wistar rats weighing between 250-330 grams (g) were randomly divided into 6 groups. Groups were defined as; Sham group (Group Sham, n=6), Amantadine 90 group (Group A-90, n=6), Amantadine 135 group (Group A-135, n = 6) Ischemia/Reperfusion group (Group I/R, n=6), Ischemia/Reperfusion + Amantadine 90 group (Group I/R-A 90, n=6), Ischemia/Reperfusion + Amantadine 135 group (Group I/R-A 135, n=6). All rats weighed before anesthesia were anesthetized with 100 mg / kg ketamine, 15 mg / kg xylazine intraperitoneally (i.p) and then intravenous cannulation was performed and abdominal areas were shaved before surgical incision. Waiting for 15 minutes after anesthesia in all groups and before surgery. A middle abdominal incision was performed in Group Sham but no intervention was performed. In Group A-90, a mid abdominal incision was made after amantadine 90 mg/kg was given intraperitoneally, but no intervention was performed. In Group A-135, a mid abdominal incision was made after amantadine 135 mg/kg was given intraperitoneally, but no intervention was performed. In Group I/R, infrarenal abdominal aorta was explored by a mid abdominal incision. Atraumatic microvascular clamp was applied to the aorta. Atraumatic vascular clamp was removed after 120 minutes of ischemia and reperfusion was performed for 120 minutes. In Group I/R-A 90 after 90 mg/kg i.p amantadine was administered, a mid abdominal incision was made and the infrarenal abdominal aorta was explored. Atraumatic microvascular clamp was applied to the aorta. Atraumatic vascular clamp was removed after 120 minutes of ischemia and reperfusion was performed for 120 minutes. In Group I/R-A 135 after 135 mg/kg i.p amantadine was administered, a mid abdominal incision was made and the infrarenal abdominal aorta was explored. Atraumatic microvascular clamp was applied to the aorta. Atraumatic vascular clamp was removed after 120 minutes of ischemia and reperfusion was performed for 120 minutes. At the end of the experiment, rats were sacrificed, and lung tissue samples were taken. In lung tissue, catalase (CAT), superoxide dismutase (SOD), malondialdehyde (MDA) levels were studied. In addition, neutrophil/lymphocyte infiltration and alveolar wall thickness scores were evaluated histopathologically. RESULTS: The weights of the rats were similar in 6 groups of 36 subjects. SOD and CAT levels were higher in Group I/R than Group Sham. SOD and CAT levels in Group I/R-A 90 and Group I/R-A 135, were higher than Group I/R and Group Sham, but no difference was found between the groups in terms of lung tissue SOD and CAT levels (p=0.400, 0.063, respectively). Tissue MDA levels were higher in Group I/R than in all groups. MDA levels of Group I/R-A 90 and Group I/R-A 135 were lower than both Group I/R and Group Sham, but there was no statistically significant difference between the groups in terms of enzyme levels (p=0,209). Histopathological examination of the lung tissue has revealed the fact that the Group I/R neutrophil/lymphocyte infiltration score was significantly higher than Group Sham, Group A-90 and Group A-135 (p=0.002, 0.002, 0.002, respectively). Group I/R-A 90 and Group I/R-A 135 were lower than Group I/R, but no significant difference was detected. Lung tissue alveolar wall thickening score levels; Group I/R was significantly higher than Group Sham, Group A-90, Group A-135 and Group I/R-A 135 (p=0.002, 0.002, 0.002, 0.002, respectively). Group I/R-A 90 level was also lower than Group I/R but it was not statistically significant. CONCLUSION: In this study, although we could not find a statistically significant difference between lung tissue biochemical values, we observed that lung tissue was histopathologically affected by I/R damage and that the damage was less with amantadine use. Especially when the alveolar wall thickening score levels were examined; We could not find any statistical difference between Group I/R-A 135 and Group Sham in which we did not cause I/R damage. At the same time, we found that Group I/R-A 135 alveolar wall thickening scores were significantly lower than Group I/R. According to these results; in the correction of İ/R damage, 135 mg/kg administration of amantadine was more beneficial than 90 mg/kg. Although there were different results in the studies of distant organ damage due to I/R damage related to amantadine, further studies are needed on this subject. Keywords: Ischemia/reperfusion, amantadine, lower extremity, lung tissue.