Heat preconditioning reduces subsequent ischemia reperfusion injury in rat kidney: a possible role for HSP-72

Improving the ability of the kidney to tolerate ischemic injury has important implication in renal transplantation. On the other hand, thermo tolerance describes the process in which hyperthermia induces a transient resistance of the stressed cells to subsequent episodes of oxidative stress. The current study was performed to evaluate the beneficial effect of heat preconditioning induced HSP-72 formation on renal ischemia reperfusion [I/R] induced damage. Four groups of rats [n=20/group] were included: Control sham-operated group [group I], heat-preconditioned sham-operated group [group II], I/R injury group [group III] and heat pre-conditioned I/R injury group [group IV]. Heat-preconditioning was induced 24h prior to sham operation and or I/R injury by increasing the core body temperature to [41 +/- 0.5°C] for 20min. The rat kidneys were subjected to ischemia by 20min of bilateral renal artery occlusion followed by reperfusion for 24 and 48h. After 24 and 48h of reperfusion, serum urea, creatinine, 24h urine out put and albumin content as well as the renal HSP-72 gene expression and MDA level were measured. Also light microscopic examination of renal tissue specimens was performed. It was found that group IV had a significant increase in renal HSP-72 gene expression compared to group III [898.36 +/- 107.82 versus 572.88 +/- 47.08 micro g/g tissue], associated with a significant improvement of its renal functions including serum urea, creatinine and 24h urine volume out put. Also there was a reduction in renal tissue injury detected by a significant decrease in urine albumin content, a significant decrease in renal MDA level and improvement in specimen microscopic picture compared to group III. The increase in HSP-72 expression and its renoprotective effect were significantly greater 24h after I/R than after 48h. Thus it can be concluded that upregulation of HSP-72 after heat preconditioning has a renal beneficial effect and can be a target for protection of renal functions during I/R injury

Vitamin C supplement modulates heat shock protein 72 gene expression in skeletal muscle of rats with type 2 diabetes

Oxidative stress has been ascribed a role in the pathogenesis of diabetes and its complications and stress proteins have been shown to protect organisms in vitro and in vivo against oxidative stress. In this study we examined the HSP72 gene expression in skeletal muscle of type 2 diabetic rats induced by oral fructose administration [66% of total caloric intake] compared to control and the possibility to increase its level by oral administration of vitamin C [100mg/kg/day for 8 weeks]. The amount of HSP72 m RNA in muscles of diabetic rats was lower than in control non-diabetic group [20.3 +/- 6.37 versus 40.52 +/- 7.49 micro g/g tissue] and its expression increased significantly by vitamin C administration [51.41 +/- 22.54 micro g/g tissue]. There was an insignificant increase in muscle insulin-stimulated glucose uptake after vitamin C administration in diabetic rats [2.59 +/- 0.66mg/g tissue versus 2 +/- 0.7mg/g tissue in diabetics not receiving vitamin C]. The plasma glucose level following vitamin C administration in the diabetic group, showed a significant negative correlation with the expression of HSP72. The concentration of malondialdehyde [MDA] as a measure of lipid peroxidation increased significantly in diabetics [2.019 +/- 0.53 micro mol/g tissue] compared to control group [0.926 +/- 0.19 micro mol/g tissue] and administration of vitamin C in diabetic rats decreased the concentration of MDA insignificantly [1.55 +/- 0.47 micro mol/g tissue] compared to the diabetic group not receiving vitamin C. In conclusion, the finding of decreased levels of HSP72 expression and decreased insulin-stimulated glucose uptake in skeletal muscle of type 2 diabetic rats raises the possibility that heat shock proteins may be involved in the pathogenesis of skeletal muscle insulin resistance in type 2 diabetics. Administration of vitamin C could be used in diabetics to increase heat shock protein HSP72 expression and to improve insulin resistance