Evaluation of Prolonged Exposure to Varenicline in Adult Rats: Haematological, Biochemical and Anatomopathological Studies.

Varenicline is a synthetic chemical substance produced from the alkaloid cytisine, used for smoking treatment, which acts as a partial agonist for α4ß2 and α3ß4 nicotinic cholinergic receptors and as a total agonist for α7 receptor. While there are studies regarding varenicline's non-smoking-related effects, as in treatment for drug dependence, there are no studies in the literature evaluating the long-term toxicity of varenicline through a physiological approach. Thus, the aim of this study was to evaluate possible toxicity through haematological, biochemical and anatomopathological parameters of prolonged exposure (30 days) to varenicline in rats. Three doses of varenicline were used: 0.03 (therapeutic dose for human beings), 0.1 and 0.3 mg/kg orally (gavage). Body-weight, water and food intake were measured weekly during treatment. On the 30th treatment day, blood and various organs were collected for haematological, biochemical and anatomopathological evaluations. The results show a decrease in some biochemical parameters in animals from the 0.1 and 0.3 mg/kg group, although the values are within the normal range of the species. There were no changes in the other evaluations performed. Together, these data indicate that prolonged exposure of rats to different doses of varenicline was not able to alter haematological, biochemical and anatomopathological parameters.

Ivermectin acute administration impaired the spermatogenesis and spermiogenesis of adult rats.

Ivermectin (IVM) is an antiparasitic agent widely used in agricultural, domestic animals and in human clinical practice. In the present study, the temporal effects of therapeutic doses of IVM in the morphometric and histological assessment of testis were studied to verify if IVM acute administration impaired the spermatogenesis and spermiogenesis of adult rats, if these effects are reversible. The testosterone levels and the plasmatic IVM levels were assessed. The results show: 1) IVM acute exposure, mainly in the higher dose, reduced the testicular volume, the tubular diameter and the germinal epithelium height; 2) no interferences on Leydig cells frequency; 3) histological studies show that tubular sections containing several histological changes indicative of spermatogenesis interruption, such as disorganization of germinal epithelium, vacuolar degeneration of the germ cells and sloughing of cells into the tubular lumen; 4) no differences in testosterone levels; 5) The IVM plasmatic levels were significantly reduced at 72h after the 0.2mg/kg. It was concluded that acute IVM impaired the spermatogenesis and spermiogenesis of rats. Probably these effects were not consequence of IVM at the Leydig cells because no effects were observed at this level. Finally, our results suggest that some testicular effects are reversible and correlated with the plasmatic levels of IVM.

Phytochemical study of Solanum lycocarpum (St. Hil) unripe fruit and its effects on rat gestation.

Solanum lycocarpum, St. Hil (Solanaceae) is a common native shrub in the Brazilian cerrado. The fruits are used in folk medicine as a hypoglycaemic agent in the management of diabetes, obesity and to decrease cholesterol levels. In this study the glycoalkaloids, solamargine and solasonine, were isolated from unripe fruits of S. lycocarpum. To evaluate the effects of the fruits on gestation, pregnant rats (n=25) were fed from day 6 to 22 with chow containing 10% of dried and ground unripe fruits. The control group (n=21) received regular chow. During and after the treatment period the dams showed reduced body weight and slower body weight gain, even with no change in food and water intake, evidencing mild maternal toxicity. Gestation was not significantly impaired, although experimental fetuses presented reduced body length at birth. Also, 20% of the treated dams showed one or two dead pups at birth. On day 22 of gestation and on post-natal day 1, the levels of metabolites of the sex hormones oestradiol, progesterone and testosterone were measured in faeces by radioimmunoassay. On post-natal day 1, tissue portions from the dams were collected for histopathological evaluation. No alterations were detected in either study. The results suggest that S. lycocarpum fruit did not impair gestation, however, it did promote mild maternal toxicity and mild fetotoxic effects if ingested as a food source during the gestation period. This study has implications for pregnant women, who employ phytotherapeutic formulations under the impression that they are harmless.

Toxicologia do praguicida aldicarb ("chumbinho"): aspectos gerais, clínicos e terapêuticos em cães e gatos

Aldicarb (Temik®), an anticholinesterase inhibitor of the carbamate group known as ‘chumbinho, is one of the most toxic of registered pesticides, and has its use restricted to agriculture in Brazil. In spite of it, aldicarb is being very often involved in severe intoxication in humans and animals. It is largely and illegally sold as rodenticide and often used in baits for intentional poisoning of companion animals. Because of this the aldicarb toxicology was reviewed empathizing its chemical properties, toxicokinetic, toxicodynamic, diagnostic and the clinical and therapeutics aspects in dogs and cats.

O aldicarb (Temik®), um agente anticolinesterásico carbamato vulgarmente conhecido como "chumbinho", é considerado um dos praguicidas mais tóxicos disponíveis comercialmente. No Brasil, embora seja registrado para uso agrícola exclusivo, tem sido freqüentemente apontado como o responsável por diversos casos de intoxicação em seres humanos e em animais. Desta forma, o presente estudo faz uma abordagem da toxicologia deste agente, enfocando as propriedades químicas, a toxicocinética, a toxicodinâmica, o diagnóstico e os aspectos clínicos e terapêuticos da intoxicação em cães e gatos.

Toxicologia do praguicida aldicarb ("chumbinho"): aspectos gerais, clínicos e terapêuticos em cães e gatos

Aldicarb (Temik®), an anticholinesterase inhibitor of the carbamate group known as ‘chumbinho’, is one of the most toxic of registered pesticides, and has its use restricted to agriculture in Brazil. In spite of it, aldicarb is being very often involved in severe intoxication in humans and animals. It is largely and illegally sold as rodenticide and often used in baits for intentional poisoning of companion animals. Because of this the aldicarb toxicology was reviewed empathizing its chemical properties, toxicokinetic, toxicodynamic, diagnostic and the clinical and therapeutics aspects in dogs and cats.

O aldicarb (Temik®), um agente anticolinesterásico carbamato vulgarmente conhecido como "chumbinho", é considerado um dos praguicidas mais tóxicos disponíveis comercialmente. No Brasil, embora seja registrado para uso agrícola exclusivo, tem sido freqüentemente apontado como o responsável por diversos casos de intoxicação em seres humanos e em animais. Desta forma, o presente estudo faz uma abordagem da toxicologia deste agente, enfocando as propriedades químicas, a toxicocinética, a toxicodinâmica, o diagnóstico e os aspectos clínicos e terapêuticos da intoxicação em cães e gatos.

Chemopreventive effects of Paullinia cupana Mart var. sorbilis, the guaraná, on mouse hepatocarcinogenesis.

Guaraná (Paullinia cupana) is originally from Amazon, Brazil. Its effects on mouse hepatocarcinogenesis have been investigated in this study. Mice were treated with N-nitrosodiethylamine (DEN), received three different doses of P. cupana added to commercial food, and euthanized after 25 weeks. Gross lesions were quantified, and preneoplastic lesions (PNL) were histologically measured. Cellular proliferation was evaluated by immunobloting for the proliferating cell nuclear antigen (PCNA). The incidence and multiplicity of macroscopic lesions were reduced. The PNL number and PCNA expression were reduced in the highest P. cupana dose. According to these results, guaraná presented inhibitory effects on DEN hepatocarcinogenesis in mice.

Evaluation of Tiletamine-Zolazepam as an Anesthetic in Quail (Coturnix coturnix japonica).

The objective of the present study was to evaluate the effects of tiletamine-zolazepam (TZ) administered alone or in combination with atropine, xylazine, and levomepromazine to quail (Coturnix coturnix japonica). The induction time, duration of hypnosis and anesthesia, and time to recovery were determined. The presence or absence of tremor, upper respiratory tract secretions, and excitability and the degree of muscular tone were also observed. The results showed that doses from 10 to 100 mg/kg TZ administered alone or in combination with xylazine or levomepromazine failed to produce anesthesia; only hypnosis was obtained in a dose-dependent manner. Immediately after injection of the drug, histopathologic examination of the site of drug injection indicated the presence of discrete acute focal myositis. After 21 days, a discrete fibrosis between muscle fibers was detected in the pectoral muscle as a sign of scarring. We conclude that the administration of TZ to a dose of 100 mg/kg does not produce anesthesia in quail. For noninvasive and minimally painful procedures requiring chemical restraint and recumbency, the recommended dose is 30 mg/kg.

Developmental expression of sexual differences in open-field behaviour and plasma cholinesterase activity in male, female and masculinized female rats / Expressão comportamental das diferenças sexuais no campo aberto e na atividade da colinesterase plasmática de ratos machos, fêmeas e fêmeas masculinizadas

Sexual differences in behaviour and metabolism are well recognized. While some of these differences are related to testosterone exposure during neonatal life, others do not depend on the organizational action of androgens during early development. The objective of the following experiments was to study the development of sexual differences in plasma cholinesterase activity and to determine if these differences were related to testosterone exposure postnatally. Open-field activity was also recorded as a behavioral indicator of the actions of testosterone on sexual differentiation of the central nervous system. Three treatment groups of animals were used: normal male, normal female, and masculinized female rats (1 mg testosterone, SC, on day 2 of postnatal life). Open-field behaviour was measured on three consecutive days just after weaning (21 -23 days of age), in association with the onset of puberty (30 - 36 days of age), or as adults (90 - 110 days of age); plasma cholinesterase activity was measured at 22, 30 - 36, and 90 - 110 days of age. As expected a sex difference in open-field activity was found between normal males and females. Postnatal androgen treatment in females decreased open-field activity in adulthood to levels similar to those found in normal males. Similar differences were observed just after weaning, but not at 30-36 days of age. In contrast, significant di

Sabe-se que algumas diferenças sexuais no metabolismo e no comportamento estão relacionadas com o efeito neonatal da testosterona e outras não sofrem esse tipo de influência. O objetivo desses experimentos foi estudar o desenvolvimento das diferenças sexuais na atividade da colinesterase plasmática e de determinar se essas diferenças seriam relacionadas com a exposição pós-natal à testosterona em ratos. A atividade geral no campo aberto foi também verificada como um indicador comportamental das ações da testosterona na diferenciação sexual do sistema nervoso central. Foram usados três grupos de animais: machos normais, fêmeas normais e fêmeas masculinizadas (1 mg testosterona. SC, no 2º. dia de vida pós-natal). A atividade geral no campo aberto foi medida durante três dias consecutivos logo após o desmame (21 - 23 dias de idade), durante o início da puberdade (30 - 36 dias de idade) e nos adultos (90 - 110 dias de idade); a atividade da colinesterase plasmática foi medida aos 22, 30 - 36 e 90 - 110 dias de idade. Como esperado, foi encontrada uma diferença sexual no campo aberto entre machos e fêmeas normais. O tratamento pós-natal com andrógeno nas fêmeas diminuiu a atividade no campo aberto na idade adulta a padrões similares àqueles observados para machos normais. Foram observadas diferenças similares logo após o desmame, mas não aos 22 e aos 30 - 36 dias de idade. Em contra

Behavioral and biochemical effects of xylazine: possible interactions between central noradrenergic-dopaminergic systems / Efeitos comportamentais e bioquímicos da xilazina: possíveis interações entre os sistemas noradrenérgico e dopaminérgico centrais

Behavioral and biochemical effects of xylazine were studied both in rats and mice. The results showed that xylazine: a) decreased the general activity of rats and mice observed in an open field; b) was unable to produce catatonia and suppressed haloperidol-induced catatonia in mice; c) increased apomorphine-induced stereotyped behavior in rats; and d) increased brain noradrenaline without effect on brain dopamine levels. These results were discussed in the light of a possible interference of xylazine with brain noradrenergic system and, thus, with the dynamic interaction between noradrenergic-dopaminergic neurons within the Central Nervous System.

Alguns efeitos comportamentais e bioquímicos da xilazina foram estudados em ratos e camundongos. Os resultados mostraram que a xilazina: a) diminuiu a atividade geral de ratos e camundongos observados em campo-aberto; b) foi incapaz de produzir catatonia e suprimiu este comportamento induzido pelo haloperidol em camundongos; c) potencializou o comportamento estereotipado induzido pela apomorfina em ratos; d) aumentou os níveis cerebrais de noradrenalina, porem não alterou aqueles de dopamina. Estes resultados foram discutidos considerando-se ação da xilazina em sislemas noradrenérgicos centrais e da interação entre sistemas noradrenérgicos e dopaminérgicos centrais.