The impact of concomitant administration of vanadium and insulin on endothelial dysfunction markers (PAI-1 and ET-1) in type 1 diabetic rats.

Endothelial dysfunction in type 1 diabetes mellitus (T1DM) is an important factor in the pathogenesis of micro- and macrovascular complications. The present study was to investigate the impact of combined vanadium and insulin for proper control and protection against endothelial dysfunction in T1DM rats. Sixty male Sprague-Dawley rats were randomly divided into six groups; control non-treated; control vanadium treated; T1DM; T1DM + insulin; T1DM + vanadium; T1DM + insulin + vanadium treated groups. At the end of the experiment (6 weeks), serum C-reactive protein, tumour necrosis factor-alpha, IL-6, endothelin-1, plasminogen activator inhibitor-1, fasting glucose serum lipogram, liver homogenate SOD activity and MDA levels were determined. Concomitant insulin and vanadium treatment improved the diabetic metabolic disturbances in addition to endothelial dysfunction and inflammatory markers. We can conclude that concomitant administration of both vanadium and insulin in T1DM decreased the risk for the development of endothelial dysfunction, micro- and macrovascular complications.

Effects of low dose of aliskiren on isoproterenol-induced acute myocardial infarction in rats.

This study examined the effects of aliskiren (Ali) (direct renin inhibitor) on serum cardiac enzymes (LDH and CK-MB), electrocardiography (ECG) changes, myocardial oxidative stress markers (MDA, CAT, and GSH) and the expression of Bcl2, HO-1, and Nrf2 genes in isoproterenol (ISO)-induced myocardial infarction (MI). A total of 40 male albino rats were allocated into four groups, (1) normal control (NC) group, (2) Ali group (rats received Ali at 10 mg/kg/day p.o. for 5 days), (3) ISO group (rats received ISO 150 mg/kg i.p. for two consecutive days at 24 h intervals), and (4) Ali + ISO group (rats received ISO + Ali at 10 mg/kg/day p.o. for 5 days from the 2nd dose of ISO). ISO group showed significant rise in serum cardiac enzymes (CK-MB and LDH), myocardial damage scores, myocardial MDA, HO-1, myocardial Nrf2 expression with significant reduction in myocardial antioxidants (CAT and GSH), and Bcl2 expression compared to the normal group (p < 0.05). ECG showed ST segment elevation, prolonged QT interval and QRS complex, and increased heart rate in ISO group. Co-administration of Ali and ISO caused significant increase in cardiac enzymes and morphology with increase in MDA, serum K, and creatinine with significant decrease in Bcl2, HO-1, and Nrf2 without significant changes in ECG parameters compared to ISO group. We concluded that low dose of Ali seems to exacerbate the myocardial injury in ISO-MI, which might be due to the enhanced oxidative stress and apoptosis.

Melatonin ameliorates brain oxidative stress and upregulates senescence marker protein-30 and osteopontin in a rat model of vascular dementia.

The aim of this study was to investigate the effect of melatonin on oxidative stress and senescence marker protein-30 (SMP30) as well as osteopontin (OPN) expression in the hippocampus of rats subjected to vascular dementia (VD). A total of 72 male rats were divided into six groups (n = 12 each) as follows: (i) untreated control (CON), (ii) sham-operated group, (iii) sham-operated + melatonin, (iv) rats exposed to VD induced by permanent bilateral occlusion of the common carotid arteries (BCCAO) leading to chronic cerebral hypoperfusion, (v) rats exposed to VD + melatonin, and (vi) rats exposed to VD + donepezil (DON). At the end of experiment, the hippocampal levels of acetylcholine (ACh), norepinephrine (NE), and dopamine (Dop) were measured. Expression of OPN was determined using immunohistochemistry, and SMP30 expression was determined using real-time PCR in the hippocampus. Hippocampal thiobarbituric acid reactive substances (TBARS) and total antioxidant capacity (TAC) were evaluated. The BCCAO group showed significantly decreased TAC (p < 0.05) and significantly increased in TBARS levels compared with the CON group. In addition, BCCAO significantly decreased (p < 0.05) the expression of both OPN and SMP30 and the levels of ACh, NE, and Dop in the hippocampus compared with CON treatment. Treatment with melatonin significantly increased OPN and SMP30 expression and ACh, NE, and Dop levels in the hippocampus with amelioration of the oxidative stress compared with BCCAO rats. Melatonin might produce a neuroprotective effect through its antioxidant action and by increasing the expression of SMP30 and OPN that is not comparable with that of DON.

Elevated basal cytosolic calcium of endothelial cells influences the post-surgical outcome in diabetic CTS.

Background Type 2 diabetes mellitus (T2DM)-induced neuropathy and ischemia-reperfusion post-surgery prolong carpal tunnel syndrome (CTS) pathology, but the effect of T2DM on the prognostic outcome of carpal tunnel (CT) release surgery needs to be investigated. Materials and methods A total of 64 individuals with CTS underwent CT release surgery. HbA1c levels identified their diabetic status. The individual prognostic outcomes were measured by nerve conduction velocity (NCV), amplitude, and latency. Measurement of [Ca2+]c and reactive oxygen species (ROS) from isolated endothelial cells (ECs) revealed the oxidative burden of the normal and diabetic CTS phenotypes. Results CTS individuals with HbA1c > 7 showed decreased NCV (≈22 m/s) and amplitude (≈4.2 mV) with increased latency (≈6 ms), compared to groups with HbA1c ≤ 7. Further to CT release surgery, the reversal of the nerve conduction to normalcy was greatly influenced by the diabetic profile of the individuals. Our results showed elevated basal [Ca2+]c and corresponding high cytosolic ROS in the ECs isolated from individuals with HbA1c > 7 compared to the diabetic and healthy control groups. Conclusion The individuals with diabetic index showed suboptimal neuronal performance pre- and post-CT release surgery. Oxidative stress mediated by high [Ca2+]c and ROS of ECs dissipates to adjoining cells worsening the pathology of the untreated CTS.

The impact of dehydroepiandrosterone on indomethacin-induced gastric lesions in rats.

UNLABELLED: Gastric ulcer is a common gastrointestinal disease. One suggested mechanism is increased oxidative stress. Puplished data showed that dehydroepiandrosterone (DHEA) may limit oxidative stress and lipid peroxidation. OBJECTIVE: To investigate the protective effect of DHEA on indomethacin-induced gastric ulcers in rats. METHODS: Forty male rats were randomly divided into four groups: l) CONTROL GROUP: receive the vehicle, 2) DHEA-treated group, 3) Indomethacin-induced ulcer group and 4) DHEA pretreated (prior to indomethacin) group. At the end of the experiment, rats were killed and the gastric contents were collected to determine the pH and acid concentration. Gastric mucosa was examined macroscopically and then parts of the tissues were collected for histopathological examination. Other parts of the gastric mucosa were homogenized to measure the levels of lipid peroxidation and oxidative stress parameters. RESULTS: Indomethacin-treated rats showed increased gastric acidity, acid concentration and ulcer index as compared to control rats. This is confirmed by histopathological studies. DHEA pre-treatment proir to indomethacin administration ameliorated all changes seen in the ulcered group. CONCLUSION: DHEA has a protective effect against indomethacin-induced gastric ulcers through decreasing acid secretion, prevention of lipid peroxidation and improving endogenous gastric antioxidant system.

Carbon dioxide sensitivity during hypoglycaemia-induced, elevated metabolism in the anaesthetized rat.

We have utilized an anaesthetized rat model of insulin-induced hypoglycaemia to test the hypothesis that peripheral chemoreceptor gain is augmented during hypermetabolism. Insulin infusion at 0.4 U kg (-1)min(-1) decreased blood glucose concentration significantly to 3.37 +/- 0.12 mmol l(-1). Whole-body metabolism and basal ventilation were elevated without increase in P(a,CO(2)) (altered non-significantly from the control level, to 37.3 +/- 2.6 mmHg). Chemoreceptor gain, measured either as spontaneous ventilatory airflow sensitivity to P(a,CO(2)) during rebreathing, or by phrenic minute activity responses to altered P(a,CO(2)) induced by varying the level of artificial ventilation, was doubled during the period of hypermetabolism. This stimulatory effect was primarily upon the mean inspiratory flow rate, or phrenic ramp component of breathing and was reduced by 75% following bilateral carotid sinus nerve section. In vitro recordings of single carotid body chemoafferents showed that reducing superfusate glucose concentration from 10 mM to 2 mM reduced CO(2) chemosensitivity significantly from 0.007 +/- 0.002 Hz mmHg(-1) to 0.001 +/- 0.002 Hz mmHg(-1). Taken together, these data suggest that the hyperpnoea observed during hypermetabolism might be mediated by an increase in the CO(2) sensitivity of the carotid body, and this effect is not due to the insulin-induced fall in blood glucose concentration.

Indirect sensing of insulin-induced hypoglycaemia by the carotid body in the rat.

The most physiologically important sensors for systemic glucoregulation are located in extra-cranial sites. Recent evidence suggests that the carotid body may be one such site. We assessed rat carotid body afferent neural output in response to lowered glucose, indirectly by measurement of ventilation, and directly by recording single or few-fibre chemoafferent discharge, in vitro. Insulin (0.4 Ukg(-1)min(-1))-induced hypoglycaemia (blood glucose reduced by ca 50% to 3.4 +/- 0.1 mmoll(-1)) significantly increased spontaneous ventilation in sham-operated animals but not in bilateral carotid sinus nerve sectioned (CSNX) animals. In both groups, metabolic rate (measured as ) was almost doubled during hypoglycaemia. The ventilatory equivalent was unchanged in the sham group leading to a maintained control level of P(a, CO(2)), but was significantly reduced in the CSNX group, giving rise to an elevation of 6.0 +/- 1.3 mmHg in P(a, CO(2)). When pulmonary ventilation in sham animals was controlled and maintained, phrenic neural activity increased during hypoglycaemia and was associated with a significant increase in P(a, CO(2)) of 5.1 +/- 0.5 mmHg. Baseline chemoreceptor discharge frequency, recorded in vitro, was not affected, and did not increase when the superfusate [glucose] was lowered from 10 mm to 2 mm by substitution with sucrose: 0.40 +/- 0.20 Hz to 0.27 +/- 0.15 Hz, respectively (P > 0.20). We suggest therefore that any potential role of the carotid bodies in glucose homeostasis in vivo is mediated through its transduction of some other metabolically derived blood-borne factor rather than glucose per se and that this may also provide the link between exercise, metabolic rate and ventilation.