Chondroprotective effect of melatonin and strontium ranelate in animal model of osteoarthritis.

PURPOSE: To analyze the action of strontium ranelate (SR) and melatonin in isolation or in association in knees, liver and kidneys of rats Wistar with induced osteoarthritis (OA). METHODS: Thirty male rats were induced to OA through an anterior cruciate ligament transection (ACLT), and treated with melatonin and SR in isolation or in association. Morphological, histopathological, histochemical and morphometric analysis were realized of the structure of the articular capsule, as well as histopathological analysis of liver and kidneys from the animals. RESULTS: The experimental model was successful. The association of the drugs presented chondroprotective pharmacodynamics. However, more successful results were identified from analysis of animals in which received melatonin in isolation, regarding biochemical parameters of glutamic oxalacetic transaminase. The prepared slide samples of liver and kidneys from groups submitted to the isolated use of SR and melatonin or the association of these drugs presented no differences, when compared to the control group. DISCUSSION: The administration of the drugs presented chondroprotective effect and prevented from the aggravation of articulate damages, and was not capable of modifying the histology of liver or kidneys. This finding suggests a safe association for the treatment of OA, however it requires further investigation in order to expand therapeutic perspectives regarding improvements of the quality of life of individuals in our society.

Essential oil toxicity on biological and reproductive parameters of Alabama argillacea (Hübner) (Lepidoptera: Erebidae).

Several studies have demonstrated the effects of essential oils on insect pests. These effects vary and affect fundamental parameters for the survival of these organisms. However, there is a scarcity of research on the effect of these substances on Alabama argillacea (Hübner) (Lepidoptera: Erebidae), the main defoliating pest of cotton (Gossypium hirsutum L.). Thus, the present study aimed to evaluate the activity of essential oils from Litsea cubeba (Lour.) Pers., Melaleuca alternifolia Cheel, Juniperus virginiana L., and Mentha spicata L., on the biological and reproductive parameters of A. argillacea and the consequent effects on the gonads of both males and females of this pest. All essential oils presented toxicity by contact in third instar larvae of A. argillacea, causing a reduction in the weight of larvae and pupae, as well as affecting the number and viability of eggs. These essential oils changed the histochemistry of the testicles, and M. alternifolia, J. virginiana, and M. spicata also affected their morphology. The histochemistry of the ovarioles was altered by the essential oils from M. alternifolia, J. virginiana, and L. cubeba. Thus, the essential oils tested in the present work are promising for the control of A. argillacea, as they are toxic and affect the development and reproduction of this key pest of cotton.

Immunohistochemical and histophysiological study of prolonged use of nandrolone on reproductive organs and fertility.

We investigated possible changes in morphology and immunohistochemistry of the uterus and ovaries of rats caused by nandrolone (ND); we also investigated effects on fertility. We used 30 rats divided into three experimental groups: control (C), control vehicle (CV) and 5 mg/kg ND. Rats treated with ND exhibited loss of estrous cyclicity with predominance of the estrus phase, increased body weight and an organosomatic index that was decreased for the ovaries, but increased for the uterus. In the ovary, we observed a reduction in primary and secondary follicles and an increase in tertiary follicles; no corpora lutea were observed. Estrogen and progesterone levels were reduced. In the uterus, the endometrium was edematous with hyperplasic glands. The cytokines, TNFα and IL6, and the apoptotic index were increased in rats treated with ND. VEGF-A was increased in the ovaries and decreased in the uterus. We conclude that ND disrupts ovarian and uterine histophysiology by establishing an anovulatory and inflammatory condition, which directly affects reproduction.

Genotoxic and mutagenic evaluation of the protective effect of exogenous melatonin in adult rats and their offspring exposed to the insecticides methomyl and cypermethrin during pregnancy.

Exposure of pregnant women to pesticides in an occupational or incidental manner has been pointed out as a possible cause of health problems in newborns. Cypermethrin and methomyl are insecticides whose active compounds and metabolites can cause harm to the health of pregnant women and their offspring. Both contribute to increases in the concentrations of oxidizing agents that damage DNA, causing mutations. Thus, the use of antioxidant substances, such as melatonin, could serve as protection against genetic damage, reducing the problems caused by insecticides. Here, we evaluated the protective effect of exogenous melatonin in adult rats and their offspring exposed to methomyl and cypermethrin during the gestational period. Thirty adult rats were divided into five groups from the first day of pregnancy: NC - negative control, Mth received 0.02 mg/kg/day of methomyl, Cyp received 0.05 mg/kg/day cypermethrin, MthMl received 0.02 mg/kg/day methomyl combined with 10 mg/kg/day melatonin, and CypMl received 0.05 mg/kg/day cypermethrin combined with 10 mg/kg/day melatonin. Blood and liver samples were collected from the dams; blood, liver, and brain samples were collected from the offspring. All tissues were used for comet assay; blood was used for micronucleus test. Our results demonstrate that cypermethrin and methomyl induce significant genetic damage in the tissues of dams and offspring. Treatment with melatonin significantly reduced cypermethrin-induced genetic damage in dams and pups; however, melatonin was not effective against the genetic damage caused by methomyl. Thus, melatonin may be considered a promising agent for the reduction of genotoxic effects induced by cypermethrin but appears to be inefficient against the genotoxic effects caused by methomyl, probably due to differences in the metabolism of each pesticide.

Análise histológica do estômago da prole de ratas Wistar submetidas ao consumo crônico de álcool durante a prenhez / Histological analysis of stomach of offspring of Wistar rats submitted to chronic alcohol consumption during pregnancy

O consumo de bebidas alcoólicas na gravidez consiste em um importante problema de saúde pública, visto que, pode causar prejuízos na organogênese de diversos órgãos, incluindo o estômago, entretanto, poucos estudos avaliam o efeito da exposição pré-natal ao álcool nesse órgão. O objetivo deste estudo foi analisar histologicamente o estômago da prole de ratas submetidas ao consumo crônico de álcool durante a prenhez. Utilizou-se 10 ratas prenhes divididas nos grupos: Controle - ratas que receberam água destilada durante todo período gestacional e Álcool ­ ratas que receberam álcool etílico absoluto (3g/kg/dia) durante todo período gestacional. Logo após o nascimento, 12 neonatos (6 machos e 6 fêmeas) de cada grupo foram anestesiados e os estômagos coletados. Posteriormente, os órgãos foram fixados e processados seguindo a técnica histológica de rotina. Foram feitas análises histomorfométricas das camadas mucosa, muscular e da parede total do estômago. Observou-se que as proles macho e fêmea expostas ao etanol apresentaram diminuição da área de epitélio, contudo, os machos também mostraram redução significativa do número de células epiteliais. Demonstrou-se ainda redução na espessura das camadas mucosa, muscular e da parede total do estômago da prole fêmea do grupo Álcool. No entanto, a camada muscular apresentou aumento significativo em sua espessura no grupo de neonatos machos expostos ao etanol. Assim, concluímos que a exposição pré-natal ao álcool provoca efeitos nocivos sobre o estômago dos neonatos, contudo, estudos futuros são necessários para melhor elucidar os mecanismos envolvidos na patogênese e possíveis consequências para os animais na fase adulta.

Consumption of alcoholic beverages during pregnancy is a significant public health issue since it can damage the organogenesis of several organs, including the stomach; however, few studies evaluate the effect of prenatal exposure to alcohol in this organ. The objective of this study was to analyze the histology of the stomach of offspring of rats submitted to chronic alcohol consumption during pregnancy. Ten pregnant rats were divided into two groups: Control - rats receiving distilled water throughout the gestation period, and Alcohol - rats receiving absolute ethyl alcohol (3g/kg/day) throughout the gestation period. After birth, 12 newborn rats (6 males and 6 females) from each group were anesthetized and their stomachs were collected. Subsequently, the organs were fixed and processed following the routine histological technique. The mucosa, muscle and total stomach were submitted to histomorphometric analyses. It was observed that the male and female offspring exposed to ethanol had a decrease in the epithelium area. However, males also showed a significant reduction in the number of epithelial cells. There was also a reduction in the layer's thickness mucosa, muscle and total stomach wall of the female offspring from the alcohol group. Additionally, the muscular layer presented a significant increase in its thickness in the group of male neonates exposed to ethanol. It can be concluded that prenatal exposure to alcohol causes harmful effects on neonates' stomachs; however, future studies are necessary to better elucidate the mechanisms involved in the pathogenesis and possible consequences for the animals in adulthood.

Protective effect of exogenous melatonin in rats and their offspring on the genotoxic response induced by the chronic consumption of alcohol during pregnancy.

Maternal alcoholism can induce serious injuries in embryonic and fetal development. The metabolism of alcohol increases the production of free radicals and acetaldehyde, molecules capable of reacting with DNA, impairing organogenesis. Melatonin is a powerful antioxidant that can act as a protective agent against DNA damage caused by genotoxic agents, such as ethanol. This study evaluated the protective effect of exogenous melatonin in rats and their offspring on the genotoxic response induced by chronic alcohol consumption during pregnancy. Twenty-five pregnant rats were divided into the following groups: NC - Negative control; ET - Rats receiving ethanol (3 g/kg/day); ET+10 M - Rats receiving ethanol (3 g/kg/day) and melatonin (10 mg/kg/day); ET+15 M - Rats receiving ethanol (3 g/kg/day) and melatonin (15 mg/kg/day); PC - Positive control (40 mg/kg cyclophosphamide). The dams and 10 pups (five males and five females) from each group were anesthetized to collect blood and liver from the dams and blood, liver and brain of neonates to evaluate the frequency of DNA damage by the comet assay. Blood was also used for the micronucleus test. The results demonstrated a significant increase in DNA damage in the blood and liver cells of dams receiving ethanol and their offspring as well as in the brain of these neonates. Treatments with melatonin (10 and 15 mg/kg/day) significantly reduced the genotoxicity caused by ethanol in the blood of dams and neonates (males and females), liver of dams and male offsprings, and in the brain of female offsprings. It was shown that only the female offspring exposed to maternal alcohol consumption showed a higher frequency of micronuclei in polychromatic erythrocytes. Consequently, exogenous melatonin may be a promising therapeutic agent against genotoxic damage induced by alcohol; however, further studies are needed to confirm these benefits.