[show abstract][hide abstract] ABSTRACT: The pathology of a gastric ulcer is complex and multifactorial. Gastric ulcers affect many people around the world and its development is a result of the imbalance between aggressive and protective factors in the gastric mucosa. In this study, we evaluated the ethanolic extract of Rosmarinus officinalis L. (eeRo); this plant, more commonly known as rosemary, has attracted the interest of the scientific community due to its numerous pharmacological properties and their potential therapeutic applications. Here, we tested the preventive effects of eeRo against gastric ulcer induced by 70% ethanol in male Wistar rats. In addition, we aimed to clarify the mechanism involved in the preventive action of the eeRo in gastric ulcers. Based on the analysis of markers of oxidative damage and enzymatic antioxidant defense systems, the measurement of nitrite and nitrate levels and the assessment of the inflammatory response, the eeRo exhibited significant antioxidant, vasodilator and antiinflammatory properties.
Food and chemical toxicology: an international journal published for the British Industrial Biological Research Association 12/2012; · 2.99 Impact Factor
[show abstract][hide abstract] ABSTRACT: In this study, the authors evaluated the ability of diphenyl diselenide (PhSe)(2) to reverse acute hepatic failure induced by acetaminophen (APAP) in mice. The animals received an APAP dose of 600 mg/kg intraperitoneally (i.p.), and then 1 hour later, they received 15.6 mg/kg i.p. of (PhSe)(2). Three hours after (PhSe)(2) administration, the animals were sacrificed and blood and liver samples were collected for analysis. The serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels were measured. The levels of reduced glutathione (GSH) and oxidized glutathione (GSSG), thiobarbituric acid-reactive substances (TBARS), 2',7'-dichlorofluorescein (DFC), catalase activity (CAT), and myeloperoxidase (MPO) activity were determined in the liver. A methyl-tetrazolium reduction (MTT) assay was also performed on the liver. Histopathological studies were conducted in all groups. Exposure of animals to APAP induced oxidative stress, increased lipid peroxidation (LPO), and the generation of reactive species, reduced the levels of GSH, and caused an increase in the MPO activity. Treatment with (PhSe)(2) reduced LPO and the formation of reactive species and inhibited the processes of inflammation, reducing the hepatic damage induced by APAP. The results of this study show that (PhSe)(2) is a promising therapeutic option for the treatment of acute hepatic failure.
[show abstract][hide abstract] ABSTRACT: Organoselenium compounds exhibit antioxidant activity, as well as a variety of biological activities, with potential pharmacological and therapeutic applications. The aim of this study was to investigate the effect of diphenyl diselenide (PhSe)(2) in reversing oxidative brain damage and mitochondrial dysfunction caused by administration of acetaminophen (APAP) in mice. Mice received a toxic dose of APAP, followed by a dose of (PhSe)(2) 1 h later. Four hours after the administration of APAP, plasma was withdrawn from the mice and used for biochemical assays of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) as markers of hepatotoxicity. Brain homogenate was examined to determine oxidative stress. Isolated brain mitochondria were examined to quantify mitochondrial transmembrane's electrical potential and mitochondrial swelling and to estimate reactive oxygen species (ROS) production. APAP administration caused an increase in plasma ALT and AST activities. APAP administration also caused a significant increase in the levels of thiobarbituric acid reactive substances (TBARS) and dichlorofluorescein oxidation in brain homogenate. Similarly, mitochondrial swelling and ROS production increased after APAP administration. APAP treatment also caused a decrease in Na(+), K(+)- ATPase activity and in mitochondrial membrane potential. These alterations observed in the brain of APAP-treated mice were restored by (PhSe)(2). Glutathione levels were decreased by APAP, but (PhSe)(2) did not reverse this change. Treatment with (PhSe)(2) after APAP administration can reverse the neurotoxicity caused by a single toxic dose of APAP. The neuroprotective effect of (PhSe)(2) is likely associated with its antioxidant properties.
Neurotoxicity Research 11/2011; 21(3):334-44. · 2.87 Impact Factor
[show abstract][hide abstract] ABSTRACT: Activation of the limbic-hypothalamic-pituitary-adrenal axis (LHPA) and the release of glucocorticoids are fundamental for the adaptive response and immediate survival of an organism in reaction to acute stimuli. However, high levels of glucocorticoids in the brain may produce neuronal injury and a decrease of Na(+)/K(+)-ATPase activity, with effects on neurotransmitter signaling, neural activity, as well as the whole animal behavior. Clomipramine is a tricyclic antidepressant that inhibits the reuptake of serotonin and norepinephrine by indirect actions on the dopaminergic system and LHPA axis. Its chronic use increases the body's ability to cope with stress; however, high doses can potentiate its side effects on memory, learning, and sensory motor function. The purpose of the present study was to compare the effect of repeated restraint stress and clomipramine treatment on Na(+)/K(+)-ATPase activity and on the behavior of male rats. Changes in the behavioral response were evaluated by measuring the memory, learning, anxiety, and exploratory responses. Our results showed that exposure to repeated restraint stress reduced levels of Na(+)/K(+)-ATPase in brain structures and changed short and long-term memory, learning, and exploratory response when compared to the control group. Exposure to clomipramine treatment increased anxiety levels and reduced Na(+)/K(+)-ATPase activity in the cerebral cortex as well as short term memory, learning, and exploratory response. In conclusion, the present results provide additional evidence concerning how repeated restraint stress and clomipramine chronically administered at higher dose levels affect the neural activity and behavior of male rats.
International journal of developmental neuroscience: the official journal of the International Society for Developmental Neuroscience 07/2011; 29(8):909-16. · 2.03 Impact Factor
[show abstract][hide abstract] ABSTRACT: This study aimed to compare the effects of repeated restraint stress alone and the combination with clomipramine treatment on parameters of oxidative stress in cerebral cortex, striatum and hippocampus of male rats. Animals were divided into control and repeated restraint stress, and subdivided into treated or not with clomipramine. After 40 days of stress and 27 days of clomipramine treatment with 30 mg/kg, the repeated restraint stress alone reduced levels of Na(+), K(+)-ATPase in all tissues studied. The combination of repeated restraint stress and clomipramine increased the lipid peroxidation, free radicals and CAT activity as well as decreased levels of NP-SH in the tissues studied. However, Na(+), K(+)-ATPase level decreased in striatum and cerebral cortex and the SOD activity increased in hippocampus and striatum. Results indicated that clomipramine may have deleterious effects on the central nervous system especially when associated with repeated restraint stress and chronically administered in non therapeutic levels.
Neurochemical Research 11/2010; 35(11):1761-70. · 2.13 Impact Factor