Prednisone and prednisolone effects on development, blood, biochemical and histopathological markers of Aquarana catesbeianus tadpoles.

Synthetic glucocorticoids are often found in surface waters and can cause harmful effects to aquatic organisms such as amphibians. In this work we evaluated the effects of the drugs prednisone (PD) and prednisolone (PL) on developmental, molecular, blood, biochemical and histological markers. Aquarana catesbeianus tadpoles were exposed for 16 days to environmentally relevant concentrations of 0, 0.1, 1 and 10 µg/L of both drugs. PD increased the transcript levels of the enzyme deiodinase III (Dio3), the hormones cortisol and T4 and delayed development. Changes in the thyroid gland occurred after tadpoles were exposed to both drugs, with a reduction in the diameter and number of follicles and an increase/or decrease in area. Also, both drugs caused a decrease in lymphocytes (L) and an increase in neutrophils (N), thrombocytes, the N:L ratio and lobed and notched erythrocytes. Increased activity of the enzymes superoxide dismutase, glutathione S-transferase and glucose 6-phosphate dehydrogenase was observed after exposure to PD. Furthermore, both drugs caused an increase in the activity of the enzymes catalase and glutathione peroxidase. However, only PD caused oxidative stress in exposed tadpoles, evidenced by increased levels of malondialdehyde and carbonyl proteins. Both drugs caused an increase in inflammatory infiltrates, blood cells and melanomacrophages in the liver. Our results indicate that PD was more toxic than PL, affecting development and causing oxidative stress.

Influence of temperature on the biomarker responses of bullfrog tadpoles (Lithobates catesbeianus) to 2-hydroxyatrazine exposure.

The influence of temperature (25 and 32 °C) on the biomarker responses of bullfrog tadpoles (Lithobates catesbeianus) to different concentrations of the atrazine metabolite 2-hydroxyatrazine (2-HA, 0, 10, 50 and 200 ng.L-1, 16 days), was evaluated. Temperature affected the activities of superoxide dismutase, glutathione S-transferase and acetylcholinesterase. The activities of catalase, glutathione peroxidase, glucose-6-phosphate dehydrogenase and carboxylesterase presented no alterations. Frequencies of micronuclei and nuclear abnormalities were also not altered. 2-HA decreased SOD activity at 25 °C and caused histopathological changes in the liver and the kidney at both temperatures, with the kidney being more affected by the combination of higher temperature and 2-HA exposure, presenting glomerular shrinkage and an increase in Bowman's space. Our results indicate that at environmentally relevant concentrations, 2-HA can cause changes in biomarker responses as well as in the morphology of liver and kidney in L. catesbeianus tadpoles. Temperature has an important influence on biomarker response and histopathological alterations.

Influence of temperature on biomarker responses and histology of the liver of American bullfrog tadpoles (Lithobates catesbeianus, Shaw, 1802) exposed to the herbicide Tebuthiuron.

Tebuthiuron (TBU) is a phenylurea herbicide that is extensively used in sugarcane fields. Owing to the low degradation rate, high water solubility, and leaching potential, TBU is believed to have harmful effects on aquatic organisms, such as anuran tadpoles. Contaminant effects can be influenced by temperature since increases in temperature are often associated with increased metabolic reactions. In this study, we evaluated the influence of temperature on the negative effects of TBU in bullfrog tadpoles (Lithobates catesbeianus) through a multi-biomarker approach. Tadpoles were exposed to 0 (control) 10, 50, and 200 ng L-1 of TBU for 16 days at 25 and 32 °C. TBU increased the transcript levels of genes involved in biotransformation (glutathione S-transferase, GST, and sulfotransferase, SULT) and antioxidant (superoxide dismutase, SOD, and catalase, CAT) enzymes. TBU exposure also increased CAT and glutathione peroxidase (GPx) activities, whereas SOD and carboxylesterase activities were decreased. The highest temperature caused a decrease in the activities of ethoxyresorufin-O-deethylase and SOD but increased the activities of GST, GPx, glucose 6-phosphate dehydrogenase, and acetylcholinesterase. No effects of temperature or TBU exposure were observed in genotoxic markers (frequencies of micronucleous and nuclear abnormalities) or in lipid peroxidation levels. Tadpoles exposed to TBU at all tested concentrations presented a higher index of biomarker responses than that of the control groups. Higher values of severity scores from histological analyses were found in the liver of tadpoles exposed to 50 and 200 ng L-1 of TBU at 32 °C compared with those of the control group at the same temperature. These results indicate that TBU and temperature increases are able to disturb the metabolic homeostasis of L. catesbeianus tadpoles after 16 days of exposure, causing substantial alterations in biomarker responses and liver morphology.

Antioxidant and antidepressant-like effects of Eugenia catharinensis D. Legrand in an animal model of depression induced by corticosterone.

This work investigated the antioxidant and antidepressant-like effects of ethyl acetate extract from Eugenia catharinensis in mice treated with corticosterone (20 mg/Kg). The animals received saline or corticosterone (21 days) and, in the last 7 days, they were treated with the extract (50, 125, 200 or 250 mg/Kg) or vehicle. After 24 h, the mice were submitted to the open field and forced swimming tests, after which the hippocampus and cerebral cortex were removed. Our results showed that the extract decreased the immobility time of mice in the forced swimming test and that the extract was able to reverse the effect caused by corticosterone. Corticosterone pre-treatment generated oxidative stress, altering antioxidant enzymes in the nervous tissue. The extract increased the catalase and superoxide dismutase activities and reversed the effects of corticosterone. In the hippocampus, the extract increased superoxide dismutase activity and reversed the increase in catalase activity elicited by corticosterone. We propose that the effects elicited by the Eugenia catharinensis are dependent on the presence of phenolic compounds (gallic acid, protocatechuic acid, syringic acid, 4-hydroxy methylbenzoic acid, chlorogenic acid, salicylic acid, caffeic acid, vanillic acid, p-coumaric acid, isoquercetin, rutin, ferulic acid, aromadendrin, galangin and apigenin) in this extract, as demonstrated by HPLC-ESI-MS/MS.

Characterisation of phenolic compounds of the ethyl acetate fraction from Tabernaemontana catharinensis and its potential antidepressant-like effect.

This study evaluates the antidepressant-like effect and analysed the qualitative and quantitative 74 phenolic standards of ethyl acetate fraction from Tabernaemontana catharinensis leaves. Acute administration of fraction in mice reduced the immobility time in forced swimming and tail suspension tests confirming its antidepressant-like activity. The anti-immobility effect elicited by this fraction was prevented by the pretreatment of mice with PCPA (100 mg kg-1), ketanserin (5 mg kg-1), SCH 23,390 (0.05 mg kg-1) or yohimbine (1 mg kg-1). A sub effective dose of the fraction produced a synergistic effect with fluoxetine (5 mg kg-1). Chromatographic analysis identified 4-hydroxybenzoic and p-coumaric acids in the ethyl acetate fraction from T. catharinensis. Capillary electrophoresis presented 7.34 ± 0.02 mg g-1 of p-coumaric acid concentration in the fraction. Therefore, it is possible that antidepressant-like effect elicited by ethyl acetate fraction from T. catharinensis be dependent on the p-coumaric acid.

Safety assessment of yerba mate (Ilex paraguariensis) dried extract: results of acute and 90 days subchronic toxicity studies in rats and rabbits.

Acute toxicity of yerba mate dried extract (YMDE) was investigated in Wistar rats (6/sex/group) from single dose of 2g/kg body weight by intragastric administration and 14days monitoring. Subchronic toxicity was investigated in Wistar rats, by intragastric administration (10/sex/group), and in New Zealand rabbits by oral administration (3/sex/group) of 2g/kg body weight for 12weeks. Toxicological parameters included clinical signs, body weight, water, and food consumption, hematological and serum parameters, and histopathological assessment. Acute YMDE administration showed no effects on survival, clinical observations, macroscopic examination of organs, body weight or food, and water consumption. Sub-chronic administration of YMDE did not change behavior, body weight, and histopatological assessment of stomach, kidney, liver, and small gut. Moreover, most of biochemical and hematological parameters remained unchanged. In summary, the results of our preclinical toxicological investigation are indicative that the YMDE is well tolerated for both single and chronic administration.