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

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

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 &gt; 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

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

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