ABSTRACT
BACKGROUND: Antioxidants such as α-tocopherol (vitamin E) and ß-carotene (vitamin A) play an important role in protective effect of repeated brief periods of ischemia, namely ischemic preconditioning (IPC). Values of these antioxidants were investigated and compared after induction of ischemia reperfusion (IR) and kidney IPC in both male and female rats. METHODS: Forty eight Wistar rats were divided randomly into six groups of 8: groups A and B (male and female controls, respectively), group C (male IR or IR cases), group D (female IR cases) and groups E and F (male and female IPC cases, respectively). In groups C and D, ischemia was induced by clamping of left renal arteries for 45 min. In groups E and F, rats underwent four cycles of 4 min of arterial clamping and 11 min of de-clamping before final 45 min ischemia induction. Afterward, serum was collected to assess the blood urea nitrogen, creatinine and vitamins E and A values. Renal tissues were obtained for histological assessments. RESULTS: α-tocopherol levels in male and female rats showed a significant increase in IPC compared with IR group (P<0.01) and also in female IPC compared with male IPC group. ß-carotene levels had no significant variations. Histological evaluation showed that IR-induced renal injuries were less in female rats. Also, protective effects of IPC were more in female rats (P<0.01). CONCLUSIONS: Renal IPC reduced damages in both male and female rats, but tissue injuries in females were decreased much more along with the increase of endogenous vitamin E.
Subject(s)
Ischemic Preconditioning/methods , Kidney/blood supply , Reperfusion Injury/pathology , Sex Characteristics , Vitamin E/blood , Animals , Blood Urea Nitrogen , Female , Ischemia , Kidney/metabolism , Kidney/pathology , Male , Random Allocation , Rats , Rats, Wistar , Renal Artery , Reperfusion Injury/metabolism , Vitamin A/bloodABSTRACT
Ischemia reperfusion injury (IR injury) is a common problem in clinical conditions. Researches have frequently revealed that ATP- sensitive potassium (KATP) channels and nitric oxide plays a role in protection against ischemic injury in skeletal muscle. The present study aimed at evaluating the possible link between this two pathways. Sixty-eight male wistar rats, were pretreated with saline, diazoxide (KATP opener; 45 mg/Kg, IP), glibenclamide (KATP inhibitor; 5 mg/Kg), or L-NAME (iNOS inhibitor; 20 mg/Kg, IP) before 3 h ischemia and 2 h reperfusion. Activities of antioxidant enzymes superoxide dismutase (SOD) and catalase (CAT), and the level of malondialdehyde (MDA) and expression of iNOS were measured in muscle tissue. Tissue MDA content was significantly increased by IR (p < 0.001). Diazoxide significantly decreased the IR-induced elevation of tissue MDA level (p < 0.05) and Glibenclamide increased MDA (p < 0.05 vs. IR group). L-NAME inhibited the effect of diazoxide on decreasing MDA (p < 0.01 vs., diazoxide+IR group) and IR decreased the activity of SOD and CAT (p < 0.01), while pretreatment with diazoxide increased activity of SOD and CAT (p < 0.01). Glibenclamide decreased SOD and CAT activity after IR (p < 0.05). L-NAME pretreatment in diazoxide-treated rats abolished the effect of diazoxide on increasing the activity of SOD and CAT (p < 0.05 vs. Diaz+IR). Expression of iNOS was increased by IR (p < 0.01 vs. Sham group). Diazoxide significantly decreased iNOS expression after IR (p < 0.05 vs. IR). L-NAME significantly decreased iNOS expression after IR (p < 0.01) in diazoxide-treated rats (p < 0.01 vs. Diaz+IR). In conclusion, the results of present study suggested a NO dependent protective effect for diazoxide against muscle IR injury.
