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The current resistance status of mosquitos to common insecticides raises the concern for innovative formulations with novel active ingredients, especially for those who can transmit pathogens. In addition to being effective, these are not allowed to harm the environment and non-target organisms. In this context, some imidazolium salts are promising candidates due to their excellent larvicidal action against Aedes aegypti, however, the understanding of their impact on environment and non-target organisms is limited. Herein, the toxicity of two imidazolium salts (1-methyl-3-octadecylimidazolium chloride (C18MImCl) and 1-hexadecyl-3-methylimidazolium methanesulfonate (C16MImMeS)) were tested in Culex quinquefasciatus larvae and their (cyto)toxic potential in Lactuca sativa seeds, mouse lung fibroblasts, human keratinocytes and Wistar rats.C16MImMeS showed excellent larvicidal activity (LC50: 24 h: 5.751 µg/mL; 48 h: 4.613 µg/mL), but negatively influenced the Lactuca sativa germination rate and size of radicles and hypocotyls, together with other phytotoxic characteristics. C18MImCl also showed being a potent larvicidal (LC50: 24 h: 3.848 µg/mL; 48 h: 3.175 µg/mL), without presenting phytotoxicity against Lactuca sativa.C16MImMeS was more cytotoxic to mouse lung fibroblast and human keratinocyte cells than C18MImCl. Besides, the lethal median toxicity of 309 mg/kg of C18MImCl for oral application in Wistar rats suggests its safe application in related non-target organisms. Altogether, this is the first work showing the larvicidal potential of these IS against Culex quinquefasciatus, including phytotoxicity and (cyto)toxicity data that are important for their release in mosquito controlling formulations. [ABSTRACT FROM AUTHOR]

Schizophrenia is a psychiatric disorder that affects 1% of the world population and is treated with antipsychotics, which may induce important biochemical and hematological alterations. Since it is necessary to verify the safety of new molecules with antipsychotic potential, the present study aimed to evaluate the oral toxicity of PT-31, a putative α2-adrenoreceptor agonist, after acute (2000 mg/kg) and repeated doses (28 days) gavage treatment, in three different doses: minimum effective dose in animal models (10 mg/kg), twice the dose (20 mg/kg), and four times the dose (40 mg/kg), as recommended by the OECD guidelines. Balb/C female adult mice were used, and biochemical, hematological, and histopathological analyses were performed. PT-31 10 and 20 mg/kg did not cause biochemical alterations related to hepatic and renal toxicity, and neither altered glycemic and lipid profiles. The preclinical dose of PT-31 also did not promote mice histopathological changes in the liver, kidney, and brain. In the hematimetric parameters, PT-31 only increased HGB at 20 mg/kg, and MCH and MCHC at 40 mg/kg. However, all the tested doses of PT-31 showed platelet increase, which must be better investigated. Therefore, further studies are needed to investigate the safety of PT-31 as a potential antipsychotic drug. [ABSTRACT FROM AUTHOR]

Meloxicam is the non-steroidal anti-inflammatory drug most used in small animals; however, studies on genotoxicity, oxidative stress, and histopathologic alterations in cardiac tissue are limited, especially at therapeutical doses used in these animals. This study evaluated the toxic effects caused by the treatment involving repeated low at higher doses of meloxicam in mice, by genotoxicity, oxidative stress, and histopathological parameters. Mice (CF1, male) received, by gavage, meloxicam at the therapeutic dose indicated for small animals (0.1 mg/kg) and at higher doses (0.5 and 1 mg/kg) for 28 days. Later, they were euthanized for blood and organ analysis. Oxidative stress was analyzed by the plasma ferric reduction capacity (FRAP) and catalase, and genotoxicity, by the comet assay and the micronucleus test. Heart, liver, lung, and kidney tissues were analyzed by the histology, and stomach and duodenum were analyzed with a magnifying glass. The relative weight of organs did not present significant alterations. However, congestion of duodenum vessels was observed at the three tested doses and caused hyperemia of stomach mucosa at 1 mg/kg. In the heart histology there was a reduction in the number of cardiomyocytes, accompanied by an increase in cell diameter (possible cell hypertrophy) dose-dependent. The highest tested dose of meloxicam also increased the DNA damage index, without alterations in the micronucleus test. Meloxicam did not affect the catalase activity but increased the FRAP (1 mg/kg). Meloxicam at the dose prescribed for small animals could potentially cause cardiac histopathologic alterations and genotoxic effects. [ABSTRACT FROM AUTHOR]

The use of orange essential oils (EOs) as a complementary treatment is very common in Brazilian popular culture. The levels of melatonin (MEL) and corticosterone (CORT) hormones were investigated simultaneously, by the Luminex™ immunoassay system in mice plasma, after Citrus aurantium and Citrus sinensis EOs inhalation for 30 min. The plasma was analyzed by headspace through gas chromatography coupled to mass spectrometry for investigation of the EO components. Mice were submitted to behavioral testing to research anxiolytic-like, sedative, and antidepressant-like effects. The inhalation of atmosphere obtained from vaporization of 10% solution of this Citrus EO separately did not affect MEL or CORT plasma levels; that is, the MEL and CORT levels did not present variation in function of the EO in the schedule used. On the other hand, the imipramine positive control used altered the level of MEL as expected. The EO constituents were detected in plasma at different ratios that is present in inhaled EO. Behavioral tests showed that the inhalation of 10% C. sinensis EO presents an anxiolytic-like and sedative effect. Thus, C. sinensis EO can be a valuable tool for treatment of the anxiety disturbs, apparently without interference with MEL and CORT physiological levels. [ABSTRACT FROM AUTHOR]

Objective: Circadian disturbances common to modern lifestyles have been associated with mood disorders. Animal models that mimic such rhythm disturbances are useful in translational research to explore factors contributing to depressive disorders. This study aimed to verify the susceptibility of BALB/c, C57BL/6N, and CF1 mice to photoperiod changes. Methods: Thermochron iButtons implanted in the mouse abdomen were used to characterize temperature rhythms. Mice were maintained under a 12:12 h light-dark (LD) cycle for 15 days, followed by a 10:10 h LD cycle for 10 days. Cosinor analysis, Rayleigh z test, periodograms, and Fourier analysis were used to analyze rhythm parameters. Paired Student's t test was used to compare temperature amplitude, period, and power of the first harmonic between normal and shortened cycles. Results: The shortened LD cycle significantly changed temperature acrophases and rhythm amplitude in all mouse strains, but only BALB/c showed altered period. Conclusion: These findings suggest that BALB/c, the preferred strain for stress-induced models of depression, should also be favored for exploring the relationship between circadian rhythms and mood. Temperature rhythm proved to be a useful parameter for characterizing rhythm disruption in mice. Although disruption of temperature rhythm has been successfully documented in untethered mice, an evaluation of desynchronization of other rhythms is warranted. [ABSTRACT FROM AUTHOR]

Abstract: Ethnopharmacological relevance: Passiflora alata is a Southern American species that constitutes many traditional remedies as well as phytomedicines used for sedative and anxiolytic purposes in Brazil. However studies on repeated treatment effects are scarce. Aim of the study: To evaluate behavioral, physiological and biochemical effects of the repeated treatment with an aqueous spray-dried extract of Passiflora alata leaves containing 2.5% (w/v) of flavonoids (PA) in mice. Material and methods: Male adult CF1 mice were treated (p.o.) for 14 days with PA (2.5; 25 or 250mg/kg). The feeding behavior was evaluated at the beginning (1h after the first administration) and at the end of the treatment (15th day). The body weight gain and food consumption were monitored along the days. On day 15 mice were evaluated on plus maze, spontaneous locomotor activity, catalepsy and barbiturate sleeping time tests. Serum glucose, lipids, ALT and AST enzymes were determined. Liver, kidney, perirenal fat, epididymal and peritoneal fat were analyzed. Results: The repeated treatment with the highest dose tested (250mg/kg) did not alter the mice behavior on open field, elevated plus maze, catalepsy and barbiturate sleeping time tests. Repeated administration of PA 250 decreased mice feeding behavior and weight gain. PA 25 and PA 250 reduced mice relative liver weight and caused mild hepatic hydropic degeneration as well as a decrease in alanine aminotransferase (ALT) serum level. Conclusions: These results indicate that Passiflora alata does not present central cumulative effects and point to the needs of further studies searching for its hepatotoxicity as well as potential anorexigenic. [Copyright &y& Elsevier]

Abstract: Extracts of Citrus aurantium L. (Rutaceae) unripe fruits have gained popularity for the treatment of obesity. Due to the wide use of C. aurantium/p-synephrine-containing products, this research was undertaken to evaluate its subchronic toxicity in mice and their actions in oxidative stress biomarkers. Groups of 9–10 mice received for 28 consecutive days a commercial C. aurantium dried extract (containing 7.5% p-synephrine) 400, 2000 or 4000mg/kg and p-synephrine 30 or 300mg/kg by oral gavage. There was a reduction in body weight gain of animals treated with both doses of p-synephrine. Organs relative weight, biochemical and hematological parameters were not altered in all treated mice. There was an increase in reduced glutathione (GSH) concentration in groups treated with C. aurantium 4000mg/kg and p-synephrine 30 and 300mg/kg. In glutathione peroxidase (GPx), there were an inhibition of the activity in C. aurantium 400 and 2000mg/kg and p-synephrine 30 and 300mg/kg treated animals, respectively, and was no alteration in malondialdehyde (MDA) levels. Thus, the results indicate a low subchronic toxicity of the tested materials in mice and a possible alteration in the oxidative metabolism. However, further tests are required to better elucidate the effects of these compounds in the antioxidant system. [Copyright &y& Elsevier]