Protective effects of some antineoplastic agents on ischemia-reperfusion injury in epigastric island skin flaps

Abstract

Neutrophil depletion has a beneficial effect on ischemic myocardium and skeletal muscle upon reperfusion. Antineoplastic agents reduce blood neutrophils effectively, and lead to neutrophil depletion. The purpose of this study was to investigate the effects of four antineoplastic agents in low doses (cyclophosphamide, cisplatinum, mitomycin-C, and 5-fluorouracil) on ischemia-reperfusion injury, using an epigastric island skin-flap model in rats. Fifty male Sprague-Dawley rats, weighing 250-300 g, were randomly divided into five groups, each consisting of 10 rats: control, cyclophosphamide, cisplatinum, mitomycin-C, and 5-fluorouracil groups. Epigastric island skin flaps (measuring 3.5 x 4 cm) were raised and subjected to 10 h of in situ ischemia, followed by 7-day reperfusion and evaluation. Treatment with antineoplastic agents (cyclophosphamide, cisplatinum, mitomycin-C, and 5-fluorouracil) was used to introduce neutropenia. Complete blood counts, cutaneous bleeding time, and skin-flap survival were evaluated. Additionally, levels of malonyldialdehyde (MDA), nitric oxide (NO), glutathione (GSH), glutathione peroxidase (GSH-Px), and superoxide dismutase (SOD) were measured from extracted skin tissue. Numbers of leukocytes and platelets were decreased in all experimental groups. However, neutropenia and thrombocytopenia were not seen. Cutaneous bleeding activity was prolonged in all experimental groups, but not above the normal value. MDA and NO levels were found to be lower in all four antineoplastic agent groups than in the control group, while GSH, GSH-Px, and SOD enzyme activities were significantly higher (P < 0.05). However, MDA and NO levels were significantly decreased in the cyclophosphamide and 5-fluorouracil groups, as compared to the cisplatinum and mitomycin-C groups (P < 0.01). Also, GSH, GSH-Px, and SOD enzyme activities were significantly increased in the cyclophosphamide and 5-fluorouracil groups, compared to the other two antineoplastic agent groups (P < 0.01). We conclude that antineoplastic agents have beneficial effects on ischemia-reperfusion injuries when their doses are carefully adjusted, by decreasing the number of leukocytes and platelets, and altering the activity of free oxygen radicals.

Protective Effect of a Nuclear Factor-Kappa B Inhibitor on Ischemia-Reperfusion Injury in a Rat Epigastric Flap Model

“…Polymorphonuclear neutrophils (PMNs) have been shown to play a pivotal role in the pathogenesis of I/R injury. 1,2 Decreasing tissue damage from reperfusion injury by administration of antineoplastic agents to decrease the number of blood PMNs, 3 or different monoclonal antibodies [4][5][6] such as fucoidin (a PMN rolling inhibitor), 7 before reperfusion to inhibit PMN-endothelial interaction has been shown to attenuate postischemic flap damage.…”

Effects of antineoplastic agents on the peripheral nerves under a surgical tissue expansion procedure: An experimental study

“…In another study, we showed that two anti- neoplastic agents, cyclophosphamide and 5-fluorouracil, decreased the number of leukocytes within 7 days, and decreased the effects of the ischemia-reperfusion injury on the epigastric island flaps. 32 In this study, two agents, cyclophosphamide and 5-fluorouracil, were more effective to decrease the ischemia-reperfusion injury in the expanded peripheral nerves. We thought that the mentioned effects of those two antineoplastic agents, cyclophosphamide and 5-fluorouracil, can decrease the effects of the ischemiareperfusion injury on the expanded peripheral nerves.…”

Tadalafil significantly reduces ischemia reperfusion injury in skin island flaps

“…[46] In our study, the epigastric island flap was chosen since it simulates microsurgical free tissue transfer, closely. [47] This model has been widely used in various experimental models on I/R injury and skin flap survival. [14,24,25,27] In Group III, a single dose of tadalafil was administered to the animals at the 30 th min of the reperfusion, because once the flaps are reperfused, mean free radical blood level is settled in certain time.…”