p-Chloro-diphenyl diselenide attenuates plasma lipid profile changes and hepatotoxicity induced by nonionic surfactant tyloxapol in rats.

Tyloxapol is a nonionic surfactant oligomer inductor of dyslipidemia, which in turn is a risk factor for liver damage. Selenium-based compounds have emerged as promising therapeutic candidates for treating different experimental disorders. This study investigated the effects of p-chloro-diphenyl diselenide (p-ClPhSe)2 on toxicity induced by Tyloxapol in rats. Plasma lipid profile, hepatic functionality and oxidative stress parameters were evaluated in adult male Wistar rats treated with (p-ClPhSe)2 (10 mg/kg; oral administration by gavage) for seven days and exposed to a single Tyloxapol injection (400 mg/kg; intraperitoneal route) 30 min after the last (p-ClPhSe)2 treatment. Tyloxapol exposure increased the plasma levels of total cholesterol, triacylglycerol, non-HDL-cholesterol and the calculated cardiac risk index (CRI). The plasma activities of alanine and aspartate aminotransferase (ALT and AST, liver function markers) were increased in rats exposed to Tyloxapol, which demonstrates a hepatic lipotoxicity. In the liver, reactive oxygen species (ROS) content was enhanced and the non-protein sulfhydryl (NPSH) levels were decreased by Tyloxapol. The data revealed that repeated treatment with (p-ClPhSe)2 reduced plasma lipid alterations and hepatotoxicity induced by Tyloxapol. Although (p-ClPhSe)2 did not reduce ROS levels increased by Tyloxapol, it increased NPSH content in the liver. Pearson's correlation coefficient revealed a positive relationship between the levels of hepatic NPSH and plasma HDL. HDL is known by eliciting antioxidant activity; therefore, the improvement in HDL function could be suggested as a therapeutic target. In conclusion, the results demonstrate the protective effects of (p-ClPhSe)2 on the hepatic lipotoxicity induced by Tyloxapol in rats.

Biochemical and histological evaluations of anti-inflammatory and antioxidant p-chloro-selenosteroid actions in acute murine models of inflammation.

This study investigated the potential p-chloro-selenosteroid (PCS) anti-inflammatory effect in different animal models of acute inflammation. In order to determine a time- and a dose-curve response of action, female adult Swiss mice (25-35g) were divided in different groups and pretreated by the intragastric route (i.g.) with PCS (5-10mg/kg) and after the specific times (5, 30 and 60min) the ear inflammation was induced with croton oil (2.5%, 20µl). The ear edema, myeloperoxidase (MPO) activity and histological analyses were performed. In a second experiment, the pleurisy model was used to determine the PCS protective effect (10mg/kg, i.g., 30min before induction) in the inflammatory and oxidative alterations induced by an intrapleural injection of a 1% carrageenan solution (0.1ml) in exudate and lung samples. Dexamethasone (1mg/kg, i.g.) was used as positive control for both models. Statistical analysis was performed through a One-Way ANOVA test followed by the Newman-Keuls' test. Pretreatment of 30min with PCS, only at a dose of 10mg/kg, decreased ear edema and the MPO activity as well as the histological alterations induced by croton oil. In the pleurisy model, PCS (10mg/kg, i.g.; 30min) reduced the leukocyte counts, histological alterations, MPO and adenosine deaminase activities, oxidative damage and the non-enzymatic antioxidant defense imbalance. PCS had a similar anti-inflammatory profile to dexamethasone; however, it showed a better antioxidant effect. PCS had anti-inflammatory and antioxidant actions in two well established inflammation models in mice.

Diphenyl ditelluride intoxication triggers histological changes in liver, kidney, and lung of mice.

Tellurium compounds may be cytotoxic to different cells types. Thus, this work evaluated the effect of diphenyl ditelluride ((PhTe)2), an organotellurium commonly used in organic synthesis, on the morphology of liver, kidney, and lung. Adult mice were acutely (a subcutaneous single dose: 250 µmol/kg) or subchronically (one daily subcutaneous dose: 10 or 50 µmol/kg for 7 and 14 days) exposed to (PhTe)2. Afterwards, the histological analyses of liver, kidney, and lungs were performed. Liver histology revealed that the hepatocytes of mice subchronically exposed to (PhTe)2 presented cytoplasmic vacuolization, hydropic degeneration, and hyperchromatic nuclei. Subchronic exposure to 50 µmol/kg (PhTe)2 also caused hepatic necrosis. Microvesicular and macrovesicular steatosis were identified in liver of mice acutely exposed to (PhTe)2. Acute and subchronic intoxication with (PhTe)2 induced changes on epithelial cells of renal tubules, namely, loss of brush border and cytoplasmatic vacuolization. Atrophy and hypertrophy, cast proteinaceous formation, and acute tubular necrosis were also identified in renal tissue. Mice subchronically exposed to 50 µmol/kg (PhTe)2 developed intra-alveolar edema and alveolar wall congestion in some areas of lungs. Acute exposure to (PhTe)2 did not cause histological changes in lungs. Our data show that (PhTe)2 may be considered a histotoxic agent for liver, kidney, and lung.

Evaluation of the pharmacological properties of salicylic acid-derivative organoselenium: 2-hydroxy-5-selenocyanatobenzoic acid as an anti-inflammatory and antinociceptive compound.

The present study evaluated the antinociceptive and anti-inflammatory effects of per oral (p.o.) administration of salicylic acid-derivative organoselenium compounds in chemical models of nociception in mice. The compounds (50 mg/kg; p.o.) were administered 30 and 60 min before the nociceptive behavior and compared to the positive-control, acetylsalicylic acid (ASA; 200 mg/kg; p.o.). In addition, a dose-response curve (25-100 mg/kg) for compounds was carried out in the formalin test. When assessed in the chemical models, acetic acid-induced writhing behavior, formalin and glutamate tests, the compounds showed the following antinociceptive profile 1B>2B>1A>2A, suggesting a chemical structure-dependent relationship. Then, the anti-inflammatory properties and toxicological potential of compound 1B were investigated. Compound 1B, similar to the positive-control, ASA, diminished the edema formation and decreased the myeloperoxidase activity induced by croton oil (2.5%) in the ear tissue. The results also indicate that a single oral administration of 1B caused neither signs of acute toxicity nor those of gastrointestinal injury. The administration of 1B did not alter the water and food intakes, plasma alanine and aspartate aminotransferase activities or urea levels and cerebral or hepatic δ-aminolevulinate dehydratase activity. Salicylic acid-derivative organoseleniums, mainly compound 1B, have been found to be novel compounds with antinociceptive/anti-inflammatory properties; nevertheless, more studies are required to examine their therapeutic potential for pain treatment.

Antioxidant effect of zinc chloride against ethanol-induced gastrointestinal lesions in rats.

The aim of the present study was to evaluate the possible effects of zinc chloride against the gastrointestinal lesions caused by oral administration of ethanol in rats. Rats were divided into five groups, namely, saline, ethanol, zn, zn+ethanol and ethanol+zn. Ethanol 70% (2 mL/kg) was administered by gavage in 36 h fasted rats. Zinc chloride (27 mg/kg, ~13 mg/kg of zinc) was given by gavage 1h before or 1h after the administration of ethanol. Oral administration of ethanol consistently induced damage in the rat glandular stomach and intestine. Zinc did not demonstrate effect per se and significantly reduced gastrointestinal lesions when administered either before or after lesion induction. Ethanol induced enhancement of thiobarbituric acid reactive substance and reactive species levels, diminished the ascorbic acid and total protein SH content as well as superoxide dismutase and catalase activity in stomach and intestine of rats. Zinc treatment prevented and reversed these alterations induced by ethanol. Stomach and intestine of rats treated with zinc presented higher zinc content than the tissues of rats treated only with ethanol. Non-protein SH content was not altered by any treatment. Results suggested that the gastrointestinal protective effect of zinc in this experimental model could be due to its antioxidant effect.

Protective action of ethanolic extract of Rosmarinus officinalis L. in gastric ulcer prevention induced by ethanol in rats.

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.

Antioxidant properties of Taraxacum officinale leaf extract are involved in the protective effect against hepatoxicity induced by acetaminophen in mice.

Acetaminophen (APAP) hepatotoxicity has been related to several cases of hepatitis, cirrhosis, and hepatic transplant. As APAP hepatotoxicity is related to reactive oxygen species (ROS) formation and excessive oxidative stress, natural antioxidant compounds have been tested as an alternative therapy to diminish the hepatic dysfunction induced by APAP. Taraxacum officinale Weber (Family Asteraceae), commonly known as dandelion, is used for medicinal purposes because of its choleretic, diuretic, antioxidant, anti-inflammatory, and hepatoprotective properties. This study evaluated the hepatoprotective activity of T. officinale leaf extract against APAP-induced hepatotoxicity. T. officinale was able to decrease thiobarbituric acid-reactive substance levels induced by 200 mg/kg APAP (p.o.), as well as prevent the decrease in sulfhydryl levels caused by APAP treatment. Furthermore, histopathological alterations, as well as the increased levels of serum aspartate and alanine aminotransferases caused by APAP, were prevented by T. officinale (0.1 and 0.5 mg/mL). In addition, T. officinale extract also demonstrated antioxidant activity in vitro, as well as scavenger activity against 2,2-diphenyl-1-picrylhydrazyl and nitric oxide radicals. Our results clearly demonstrate the hepatoprotective effect of T. officinale against the toxicity induced by APAP. The possible mechanisms involved include its scavenger activities against ROS and reactive nitrogen species, which are attributed to the content of phenolic compounds in the extract.

Vitamin E decreased the activity of acetylcholinesterase and level of lipid peroxidation in brain of rats exposed to aged and diluted sidestream smoke.

INTRODUCTION: The biological systems of both smoker and passive smoking suffer changes caused by toxic compounds from cigarette smoke such as inflammation, lipid peroxidation, and deficiency of vitamin E. The aim of the present study was to evaluate the effect of vitamin E on acetylcholinesterase (AChE) activity and the lipid peroxidation level in the brain of rats in the model of exposure to aged and diluted sidestream smoke (ADSS). METHODS: Adult male Wistar rats (200-300 g) were exposed to ADSS for 4 weeks and treated with vitamin E (50 mg/kg/day) loaded by gavage. In the first, second, third, and fourth weeks, animals were concomitantly exposed to the smoke of 1, 2, 3, and 4 cigarettes/day, respectively. The duration of each exposure was 15 min, daily. RESULTS: For rats exposed to ADSS, the AChE activity and lipid peroxidation level increased in the striatum, cerebral cortex, and cerebellum. In contrast, the activity of AChE and the level of lipid peroxidation decreased in the smoke group treated with vitamin E. CONCLUSIONS: The results suggest that the rats exposed to ADSS and treated with vitamin E significantly reduced the raised activity of AChE and level lipid peroxidation from the brain structures studied. The study, therefore, concludes that vitamin E could be considered as a therapeutic agent in this type of exposure.