Role of serotonin in cerebral oxidative stress in rats.

Serotonin or 5-hydroxytryptamine (5-HT) is a monoamine neurotransmitter synthesized by the aromatic amino acid decarboxylase using 5-hydroxytryptophan (5-HTP) as a substrate. It was recently shown that serotonin and its precursor have powerful antioxidant properties. The aim of this study was to evaluate the effect of reduction in 5-HT levels by parachlorophenylalanine (pCPA) and their restoration by 5-HTP administration on lipid peroxidation and antioxidant status in rat brain. Serotonin levels were decreased by p-chlorophenylalanine administration. The effect of p-chlorophenylalanine was counteracted by the intraperitoneal administration of 5-hydroxytryptophan. We evaluated the concentration of serotonin, malonyl dialdehyde and the status of antioxidants (GSH, catalase and superoxide dismutase) in brain. The results showed that p-chlorophenylalanine (300 mg/kg) induced a depletion of serotonin concentration and antioxidant status, as well as enhancing malonyl dialdehyde concentration in brain. The exogenous administration of 5-hydroxytryptophan prevented all effects induced by p-chlorophenylalanine in brain tissue. The recovery of the neurotransmitter concentration in brain was related to the reduction of lipid peroxide generation and improved antioxidant status. In conclusion, our study supports the view that the antioxidant properties of serotonin protect against basal oxidative stress in brain.

Ovariectomy exacerbates oxidative stress and cardiopathy induced by adriamycin.

Ovarian hormone depletion in ovariectomized experimental animals is a useful model with which to study the physiopathological consequences of menopause in women. It has been suggested that menopause is a risk factor for the induction of several cardiovascular disorders. In the present study we analyzed the effects of ovarian hormone depletion by ovariectomy (OVX) in a model of oxidative stress and cardiopathy induced by adriamycin (AD). To evaluate these effects, we measured parameters related to cardiac damage (creatinine kinase, lactate dehydrogenase, aspartate aminotransferase and alanine aminotransferase) and oxidative stress (malondialdehyde, catalase, superoxide dismutase, glutathione peroxidase, reduced glutathione, nitric oxide and carbonyl proteins) in cardiac tissue and erythrocytes. OVX was found to alter all markers of oxidative stress and cell damage in cardiac tissue. Similarly, the OVX-derived loss of ovarian hormones enhanced cardiac damage and oxidative stress induced by AD. Our results suggest that antioxidant status in cardiac tissue and erythrocytes is seriously compromised by OVX during the cardiomyopathy induced by AD in experimental animals. In conclusion, the absence of hormones caused by OVX or menopause may induce or accelerate pre-existing cardiovascular dysfunctions.

Estradiol and catecholestrogens protect against adriamycin-induced oxidative stress in erythrocytes of ovariectomized rats.

The beneficial effect of estrogens and catecholestrogens against oxidative stress associated tissue injury has been observed in different experimental model. The administration of adriamycin (AD) has been shown to enhance oxidative stress in different tissues. The lack of estrogens during ovariectomy (OVX) also induces oxidative damage in several tissues. However, the antioxidant properties of estrogens and catecholestrogens administration have not been evaluated in erythrocytes and plasma from ovariectomized animals in presence or not of AD toxicity. We have assessed the antioxidant capacity of 17beta-estradiol (17beta) and catecholestrogens against oxidative stress in erythrocytes and plasma induced by OVX in control animals or AD-treated animals. We analyzed the level of lipid peroxides, carbonyl proteins and reduced glutathione (GSH) as well as glutathione peroxidase (GPx) and superoxide dismutase (SOD) activities in plasma and erythrocytes. The results showed that AD, OVX and its combination increased lipid peroxides and carbonyl proteins, as well as reduced glutathione, superoxide dismutase and glutathione peroxidase activities in plasma and erythrocytes. The administration of 17beta and its metabolites (2- and 4-hydroxyestradiol) prevented all markers of oxidative stress induced by OVX in control and AD-treated animals. In conclusion, the administration of estrogens and cathecolestrogens counteract the oxidative stress in erythrocytes and plasma induced by OVX in presence or not toxic injury.

Protective effect of red wine on oxidative stress and antioxidant enzyme activities in the brain and kidney induced by feeding high cholesterol in rats.

The effect of red wine (400 ml/70 kg) on brain and kidney oxidative stress and antioxidative enzymes activities induced by cholesterol-enriched diet (supplemented with 1.65% of cholesterol (w/w) for 4 weeks) was studied in rats. When red wine (Montilla-Moriles, Cordoba, Spain) was simultaneously supplemented to high-cholesterol diet for 4 weeks, total cholesterol and lipid peroxidation products in the brain, kidney and erythrocytes significantly decreased compared with the high-cholesterol, while GSH content and antioxidative enzymes activities enhanced. On the other hand, the urinary excretion of urea, creatinine and albumin decreased significantly. These results suggest that red wine may have a neuro-nephroprotective effect against oxidative stress and hypercholesterolemia.

Effect of 17-beta-estradiol administration during adriamycin-induced cardiomyopathy in ovariectomized rat.

The incidence of cardiovascular diseases in humans differs in relation to the age of the patient. Although women suffer less than men from cardiovascular disorders during 15-55 years, after this period the incidence is equivalent in both sexes. This data suggests a cytoprotective effect of estrogens against cardiovascular disease. The estrogens, especially 17-beta-estradiol, are important antioxidant molecules with potential cytoprotective properties during oxidant/antioxidant disbalance induced by oxidative stress. Oxidative stress is often the underlying mechanism during vascular alterations and cardiac damage. The present study evaluated the role of ovariectomy and/or 17-beta-estradiol administration on antioxidant status and lipid peroxidation during cardiac injury induced by adriamycin. Different parameters were measured, including hemodynamic response (arterial pressure and cardiac frequency), lipid peroxidation products (malondialdehyde), protein carbonylation, antioxidant status (reduced glutathione, glutathione peroxidase, superoxide dismutase and catalase), and cardiac injury (creatinine kinase, lactate dehydrogenase, aspartate and alanine aminotransferase). Our study showed that 17-beta-estradiol reduced all of the parameters related to oxidative stress and cardiac injury in ovariectomized rats treated with adriamycin.

Red wine prevents brain oxidative stress and nephropathy in streptozotocin-induced diabetic rats.

We have studied the effects of red wine on brain oxidative stress and nephropathy in streptozotocin (STZ)-induced diabetic rats. Diabetes was induced in Wistar rats with a single intraperitonally injection of STZ (50 mg/kg). Two weeks before and four weeks after injection, red wine was given orally in both normal and diabetic rats. Blood samples were taken from the neck vascular trunk in order to determine the glucose, triglycerides, total cholesterol, HDL-cholesterol (HDL-c), atherogenic index (AI), total protein, blood urea nitrogen (BUN), creatinine, insulin, lipid peroxidation products, reduced glutathione (GSH) and superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) activities. As well, we estimated the lipid peroxidtion, GSH and SOD, GSH-Px and catalase activities in brain and renal homogenates, and the excretion of albumin, proteins and glucose in urine over 24 h period. The administration of STZ caused significant increases in levels of glycosuria, proteinuria, albuminuria, glycemia, total cholesterol and AI, as well as in lipid peroxidation products in the brain, plasma and kidney, whereas it decreased the GSH content and SOD, GSH-Px and catalase activities. Treatment with red wine significantly prevented the changes induced by STZ. These data suggested that red wine has a protective effect against brain oxidative stress, diabetic nephropathy and diabetes induced by STZ, as well as it protects against hypercholesterolemia and atherogenic risk.

Protective effect of Montilla-Moriles appellation red wine on oxidative stress induced by streptozotocin in the rat.

This study evaluated the protective effect of Montilla-Moriles appellation red wine (Cordoba, Spain) on oxidative stress, course and intensity of symptoms in experimental diabetes induced by the injection of streptozotocin in male Wistar rats. The rats were injected with a single dose of streptozotocin (60 mg/kg i.p.) and given water and red wine separately. After 4 weeks of treatment, blood samples were obtained to determine sugar and fructosamine concentrations in blood plasma, serum insulin concentration, and percentage of glycosylated hemoglobin in blood. The kidney, liver, and pancreas were removed to determine lipid peroxidation levels, reduced glutathione content, and antioxidative enzyme activity. A significant increase of glucose concentration in urine was found in the rats after injecting the streptozotocin. The administration of red wine before streptozotocin elevated reduced glutathione content and antioxidative enzyme activity, while lowering the lipid peroxidation level. Moreover, the red wine induced decreased levels of glycemia, plasma fructosamine and percentage of glycosylated hemoglobin, while increasing levels of insulin. These data suggest that red wine has a protective effect against oxidative stress and diabetes induced by streptozotocin.

Melatonin prevents oxidative stress and hepatocyte cell death induced by experimental cholestasis.

The induction of oxidative stress precedes liver injury during experimental obstructive jaundice (OJ). In this sense, different evidences suggest that melatonin (MEL), as antioxidant, may be useful in the protection against apoptosis and necrosis during experimental cholestasis. In addition, we will also assess if MEL-dependent protection is related to a recovery of antioxidant status disturbances induced by OJ. Cholestasis was achieved by double ligature and sectioning of the principal bile duct. MEL was injected intraperitoneally (500 microg/kg/day). Lipid peroxidation was evaluated by the measurement of malondialdehyde (MDA) content in liver. Different parameters related to antioxidant status, such as reduced glutathione (GSH), glutathione peroxidase (GPx), catalase and superoxide dismutase (SOD) were determined in liver. Liver injury was assessed by alanine amino-transferase (ALT) in serum, histological examination, DNA fragmentation and TUNEL assay. The activation of perisinusoidal stellate cells was evaluated by immunohistochemical measurement of alpha-smooth muscle actin in liver sections. The induction of OJ increased all the parameters related to apoptosis and necrosis in liver. The induction of liver injury was associated with stellate cell activation, as well as an increase in MDA (p < 0.0001) and a reduction in GSH, GPx, catalase and SOD content (p < 0.0001) in liver. MEL reduced hepatic apoptosis and necrosis (p < 0.004) with a significant improvement in all oxidative stress markers. In conclusion, our results showed that MEL recovered the antioxidant status and reduced apoptosis and necrosis induced by experimental cholestasis.

Effect of glucocorticoids on 3-nitropropionic acid-induced oxidative stress in synaptosomes.

The present study with rat striatal and cortical synaptosomes evaluated the effect of dexamethasone (300 microg/kg i.p./day) with and without simultaneous adrenalectomy on the oxidative stress induced by 3-nitropropionic acid (20 mg/kg/day for 4 days). Adrenalectomy enhanced the oxidative stress induced by 3-nitropropionic acid. These changes were prevented by previous and simultaneous administration of dexamethasone. Adrenalectomy alone induced oxidative stress with decreases in succinate dehydrogenase activity. Our results revealed that adrenal glucocorticoids, and especially dexamethasone (synthetic glucocorticoid), have a protective effect against oxidative stress induced by 3-nitropropionic acid in some brain regions of the Wistar rat.

Protective melatonin effect on oxidative stress induced by okadaic acid into rat brain.

We studied the effect of melatonin on the oxidative changes produced by the intracerebroventricular (i.c.v.) injection of okadaic acid (200 ng/kg BW) in the Wistar rat. The effects of okadaic acid were evaluated as changes in the quantity of lipid peroxides, reduced glutathione content (GSH) and activity of antioxidative enzymes. Okadaic acid caused lipid peroxidation (5.35 +/- 0.47 micro mol/g tissue in the i.c.v. vehicle group versus 10.14 +/- 0.88 micro mol/g tissue in the okadaic acid group, P < 0.001), GSH consumption (0.115 +/- 0.0065 micro mol/g tissue in the i.c.v. vehicle group versus 0.024 +/- 0.0021 micro mol/g tissue, P < 0.001), and a reduction in the activity of GSH-peroxidase, GSH-reductase and GSH-transferase between 60-80%. All these changes were prevented by pre-injection of 4.5 mg melatonin per kg BW 2 hr before okadaic acid. These findings indicate: (i) okadaic acid induces a status of oxidative stress in the brain, characterized by a high level of lipid peroxidation, decreases in GSH content and diminished activities of antioxidative enzymes, and (ii) melatonin prevents the deleterious effects induced by okadaic acid. In conclusion, the results show the ability of melatonin to modify the neural response to okadaic acid with the protective mechanism likely involving the antioxidative processes of melatonin.