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

changes in expression of platelet derived growth factor [PDGF] and PDGF receptor in rat corpus cavernosum after exposure to in vivo hypoxia and cigarette smoking

Platelet derived growth factor [PDGF] over activity has been implicated in atherosclerosis and several fibrotic conditions including lung and kidney fibrosis, liver cirrhosis and myelofibrosis. Low oxygen tension [hypoxia] and cigarette smoking is a known stimulus for transcriptional induction of [PDGF] ligand and receptor gene. We studied the expression of [PDGF-A] and [PDGFR-beta] in adult male rat isolated corpus cavernosum under hypoxic and cigarette smoking conditions being associated with induction of fibrosis which may lead to erectile dysfunction. Fifty adult male albino rats were used in this experiment. They were divided into 5 groups. Group I [n=10], served as control group. Group II [n=10] rats exposed to acute hypoxia. Group III [n=10] rats exposed to chronic hypoxia. Group IV [n=10] rats exposed to acute cigarette smoking. Group V [n=10] rats exposed to chronic cigarette smoking. In all groups at the end of each experiment corpora cavernosa of all rats were carefully dissected and freed from surrounding tunica albuginia then frozen in -80°C for subsequent reverse transcriptase polymerase chain reaction [RT-PCR]. In all groups of rats PDGF-A and PDGR-m RNA were measured. There was significant increase in PDGF-A mRNA and PDGF- beta receptor in acute hypoxic group, chronic hypoxic group, and chronic cigarette smoking groups of rats compared to control group. It was found that hypoxia, whether, acute or chronic have similar effect of increasing PDGF-A mRNA and PDGF-beta receptor as well as chronic cigarette smoking group of rats. This may lead to erectile dysfunction

Comparative effect of antioxidants and l-arginine treatment on nerve conduction velocity and regeneration in streptozotocin-induced diabetic rats

Diabetic polyneuropathy [DPN] is the most common chronic complication of diabetes. In the last two decades it has become increasingly evident that underlying vascular and metabolic mechanisms emerged as a prominent pathogenetic factors for DPN. Oxidative stress is increased in both human and experimental diabetes and has been related to the development of diabetic neuropathy. Vascular factors include increased peripheral resistance also have been implicated in the pathogenesis of experimental diabetic neuropathy [EDN]. It seems still controversial, whether EDN is primarily of vascular or metabolic origin and the aim of the present study was to evaluate the possible contribution of two pathways to the development of such neural complications in type II diabetic animals. Ninety male albino rats were included. The animals groups were as follows: Group I: Control rats which were injected by intraperitoneal [i.p.] by vehicle solution alone, Group II: Diabetic rats not receiving any form of treatment [with fasting blood glucose level above 300mg/kg], Group III: Diabetic rats received daily subcutaneous insulin injection in a dose IIU/day, Group IV: Diabetic rats received intramuscular injection of Vitamin E in a dose 300mg/kg BW, three times/week, Group V: Diabetic rats received intramuscular injection of Vitamin E in a dose 600mg/kg BW, three times/week, Group VI: Diabetic rats received subcutaneous insulin [IIU/day], and intramuscular injection of Vitamin E [300mg/kg BW, three times/week], Group VII: Diabetic rats received subcutaneous insulin [IIU/day], and intramuscular injection of Vitamin E [600mg/kg BW, three times/week], Group VIII: Diabetic rats received daily intragastric L-arginine in a dose of 50mg/kg BW, Group IX: Diabetic rats received daily intragastric L-arginine in a dose of 50mg/kg BW, and subcutaneous insulin [IIU/day]. After 4 weeks, nerve conduction velocity studies were performed, serum glucose was measured, and sciatic nerves malondialdehyde [MDA], glutathione peroxidase [GTPx], endothelial nitric oxide synthase [eNOS] were measured. Diabetic rats had significant higher serum glucose levels, oxidative stress markers, lower eNOS, with delayed nerve conduction velocity [NCV] and lower amplitude of muscle contraction [AMC] as compared with the control group. Treating rats with insulin corrected serum glucose to control values. Treating rats with vitamin E significantly reduced oxidative stress markers, and corrected NCV and improved AC. L-arginine treatment had no effect on serum glucose, oxidative stress markers, but significantly improved NCV and AMC. It can be concluded that EDN is a multifactorial disease, caused by hyperglycemia, oxidative stress and vascular impairment. Conjugate treatment with vitamin E especially in higher doses [600mg/kg B. W.] with insulin could be of great value. Moreover correction of impaired nerve blood flow by drugs that induce NO has proved to be efficient in the protection against, and correction of EDN