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  • Title: Nonsynergistic effects of trimetazidine and selenium combination therapy on renal ischemic-reperfusion injury in rats.
    Author: Karayaylali I, Emre M, Seyrek N, Yildiz SM, Erdogan S, Balal M, Paydas S, Tuncer I, Alparslan N.
    Journal: Adv Ther; 2004; 21(1):47-60. PubMed ID: 15191157.
    Abstract:
    Reactive oxygen species (ROS) have been postulated to play a major role in postischemic acute renal injury. Moreover, lipid peroxidation has been described as an important pathway of ROS-induced postischemic acute renal failure. To evaluate effects of selenium (Se) and trimetazidine (TMZ) on postischemic renal failure, renal tissue malondialdehyde (MDA) and superoxide dismutase (SOD) concentrations were measured in Wistar rats with ischemic renal failure. Treatment groups consisted of rats treated with TMZ (5 mg/kg orally) or Se (30 microg/kg orally) or TMZ+Se for 15 days. Ischemic groups consisted of rats with clamped left renal arteries for 1 hour. Before left renal arterial clamping, right nephrectomy was performed; after 24 hours, left nephrectomy was done. The animals were divided into 5 groups. Group 1 (n=7) was the nonischemic control group without treatment; Group 2 (n=6) was the ischemic control group treated with physiologic solution; Group 3 (n=5) received TMZ; Group 4 (n=5) received Se; and Group 5 (n=6) received TMZ+Se for 15 days. After TMZ and Se treatment, right renal tissue MDA significantly decreased in Groups 3-5 when compared with those in Group 1. There was no significant difference between nonischemic and ischemic renal tissue MDA in Groups 3, 4, and 5. Postischemic renal tissue SOD levels were higher than nonischemic levels in Group 3. In Groups 4 and 5, no significant differences were observed between nonischemic and ischemic renal tissue SOD levels. Moreover, total scores obtained from histopathologic evaluation of ischemic and nonischemic kidney samples in Groups 3, 4, and 5 were similar, but these scores in Group 2 were significantly different from those of Groups 3, 4, and 5. These results indicate that, under these study conditions, TMZ, Se, and TMZ+Se treatments prevent lipid peroxidation in ischemic and nonischemic renal tissue. Moreover, these treatments prevent histologic findings of postischemic-perfusion renal injury.
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