Study On Antioxidative And Anti-inflammatory Effects Of Repaglinide

With the improvement of people’s living standards, the incidence of diabetes isincreasing in the world. Studies have found that oxidative stress and inflammation are thecritical pathophysiological factors causing diabetes and its complications. Studies haveshown that normal clinical dose of repaglinide could improve the parameters related tooxidative stress and inflammation in diabetic patients. Repaglinide is a highly lipophilicbenzoic acid derivative. The data about a direct anti-oxidative activity such compoundswere reported. Type1diabetic model was established to explore whether repaglinide hadanti-inflammatory and antioxidant effect and the relationship between anti-inflammatoryeffect and insulin secretion promotion effect, hypoglycemic effect and antioxidant effect.In this study, we use the method of high-dose streptozotocin injection to estabilsh type1diabetic experimental model. SD rats were randomly divided into normal control group,normal treatment group, diabetic control group, repaglinide treatment group andindomethacin treatment group. Then the repaglinide group and normal treatment groupwere treated with1mg/kg repaglinide, the indomethacin group treated with5mg/kgindomethacin. The normal control group andthe diabetic group were treated with the samevolume of CMC-Na. Half of animals were sacrified at the end of the4th week and theremaining rats were sacrified at the end of the8th week. During the period of drugadministration, body weight was measured every two days, food intake, water intake andglucose level were measured once a week, and rats’ state were observed daily. The organsof rats were harvested for calculating the visceral index. Serum samples were collected forthe measurement of H2O2, SOD, GSH, MDA, CRP, IL-6, TNF-α, NF-κB and AP-1in allgroups.After4weeks of treatment, there were no significant differences onrats’ body weight,glucose level, food intake, water intake, thymus index, spleen index, liver index, heartindex, left kidney index and pancreas index compared with diabeticcontrol group. Indiabeticgroup treated with repaglinide, the level of H2O2, MDA, CRP, TNF-α, NF-κB andAP-1were decreased significantly (p<0.05), and the levels of SOD and GSH weresignificant increased (p<0.05), compared with diabetic rats. The level of IL-6of repaglinidegroup was no significantly changing compared with diabetic group. Normal treatmentgroup and the control group had no significant change. After8weeks of treatment, compared with diabetic group,the levels of H2O2, MDA, CRP and TNF-α in diabeticrepaglinide group were decreased significantly (p<0.05), andthe level of NF-κB and AP-1expression reduced significantly (p<0.05). Moreover, the levels of SOD and GSH inrepaglinide group were increased significantly (p<0.05). There were no significantdifferences on rats’ body weight, glucose level, food intake, water intake, thymus index,spleen index, liver index, heart index, left kidney index and pancreas index compared withdiabetic group.And the level of IL-6in repaglinide group was no significantly changingcompared with diabetic group. Repaglinide had no significant effect on normal rats.This study demonstrates that antioxidant and anti-inflammatory effects of repaglinideon diabetic rats were independent of hypoglycemic effect. Repaglinide may exertanti-inflammatory effect related to antioxidant effect, through down-regulating theexpression level of NF-κBor AP-1, thus decresing the level of inflammatory cytokines.