Melatonin Administration Prevents Placental and Fetal Changes Induced by Gestational Diabetes.

Gestational diabetes mellitus (GDM) promotes changes in the placenta and fetuses, due to oxidative stress. Antioxidants can reduce oxidative stress in the placenta. We tested the hypothesis that melatonin (Mel) can prevent these effects in the placenta and fetuses, analyzing their histology, histochemistry, morphometry, and immunohistochemistry. Thirty albino rats were used, divided into groups: CG-pregnant non-diabetic rats; GD-pregnant diabetic rats; GD + Mel-pregnant diabetic rats treated with melatonin. Diabetes was induced by streptozotocin at a dosage of 50 mg/kg i.p. Melatonin was administered in daily injections of 0.8 mg/kg i.p. Melatonin prevented the placental weight and fetal weight and length from increasing, in addition to histomoformetric, histochemical, and immunohistochemical changes in the placentas, compared to the placentas of diabetic females (GD). Thus, we conclude that melatonin has a great potential to prevent placental changes due to GDM.

Renal and hepatic changes in the offspring of rats that received biological insecticides during pregnancy and lactation.

Bacillus thuringiensis insecticides have been considered safe, being an alternative to the use of synthetic insecticides. However, studies have shown the effects of Bt Cry toxins on various organs, compromising their functions. The objective of this work was to test whether the administration of biological insecticides based on B. thuringiensis in pregnant rats will cause histopathological changes in the liver and kidneys, as well as in the levels of toxicity biomarkers, of their puppies in adulthood. Twenty rats, 90 days old, were used, divided into four groups: GC - Pregnant rats, GX - Pregnant rats that received XenTari®, GDi - Pregnant rats that received Dipel® and GDe - Pregnant rats that received deltamethrin. Insecticides were administered by gavage at a dosage of 1 mg/100 g/day (GX and GDi), and 2 mg/Kg/day (GDe) during pregnancy and lactation. In the animals of the groups whose matrices received the insecticides, there was a reduction in the levels of the biomarkers of toxicity alanine aminotransferase (ALT), aspartate aminotransferase (AST), urea and creatinine, about the control group. The biological insecticides promoted histopathological changes in the liver, with the presence of portal vein, centrilobular and sinusoidal capillaries congestion, and in the kidney, presence of cortical congestion and reduction of the subcapsular space. Histochemical evaluation in the liver demonstrated a significant reduction in glycogen in the groups that received insecticides when compared to the control group, whereas for collagen fibers in both the liver and the kidneys, no differences were observed between the experimental groups. The morphometry of the liver revealed a significant reduction in the lobular parenchyma and an increase in the non-lobular parenchyma, and in the kidney, there was a reduction in the diameter and volume of the glomerulus and Bowman's capsule of the animals whose matrices received both biological and synthetic insecticides. Thus, it is concluded that the biological insecticides XenTari® and Dipel® in sublethal doses in pregnant rats promote changes in the liver and kidney of the offspring similar to the insecticide deltamethrin, which extend into adulthood.

Protective action of melatonin on diabetic rat testis at cellular, hormonal and immunohistochemical levels.

The aim of the present study was to analyze the effects of melatonin treatment on diabetic rat testes. Fifty albino rats were divided into the following groups: CG: control group; GD: placebo-induced and placebo-treated mice; GDI: insulin-induced and post-confirmation diabetes-induced rats; GDM: diabetes-induced and melatonin-treated post-confirmation mice and GDMS: diabetes-induced and melatonin-treated mice simultaneously. Melatonin was administered at a dose of 10 mg/kg in drinking water every day for 20 days at night. Diabetes was induced by streptozotocin (60 mg/kg) and confirmed after the fifth day of induction. Insulin was administered at 5 IU (international units)/day at different times of the day for 20 days. The testes were submitted to histopathological, morphometric, immunohistochemical and oxidative stress analysis. Melatonin moderately decreased glycemic levels, protected weight loss and morphometric changes in the testicles, increased antioxidant enzyme levels and stabilized plasma testosterone and androgen receptor levels and decreased inflammatory markers in the testicles. Showing its potential to mitigate diabetes effects.

Effect of melatonin on gonad and thyroid development of offspring of hypothyroid pregnant rats.

We investigated the effects of melatonin on rats with induced hypothyroidism during gestation as well as its effect on the development of the gonads of their offspring. Fifteen pregnant rats were divided into three groups: GC, rats without induced hypothyroidism; GH, rats with induced hypothyroidism; GHM, rats with induced hypothyroidism plus melatonin. Hypothyroidism was induced by oral administration of 6-propyl-2-thiouracil and melatonin was applied subcutaneously. Treatments were performed during gestation and lactation. For the matrices, we evaluated the number of pups, body weight gain, ovarian weight, thyroid weight, organosomatic index, thyroid stimulating hormone (TSH) dose and thyroid morphometry. For the pups, weight gain, TSH, weight, morphometry of the gonads and organosomatic index were analyzed, as well as the cell proliferation index. TSH was elevated only in the matrices of GH animals. Melatonin prevented reduction of ovarian and thyroid weight, number of pups, follicular diameter and thyroid epithelial proportion of the matrices with hypothyroidism. The offspring of rats of the GH group exhibited less body weight gain, gonad and thyroid weight, and gonad cell proliferation index compared to the offspring born of rats of the GC and GHM groups. Melatonin prevented the effects of maternal hypothyroidism on the offspring of rats.

Histopathology of organs from neonate offspring born to female rats exposed to sublethal doses of biological and synthetic insecticides / Histopatología de órganos de ratas recién nacidas sometidas a dosis subletales de insecticidas sintéticos y biológicos

The current annual consumption of insecticides in agriculture in Brazil is over three million tons. The exposure happens through food that is contaminated with toxic waste and respiratory and dermal absorption. Biological control with Bacillus thuringiensis Berliner (Bt) has assumed increasing importance replacing the use of conventional insecticides. However, the tests used to justify approval for use and market release of Bt products, and the protocols used to assess the development of toxicity, are extremely superficial. In addition, more studies comparing effects between males and females and during pregnancy and lactation have not been conducted. Thus, the hypothesis tested in this study was if the administration of the XenTari® WG (Bacillus thuringiensis subsp. Aizawai) biological insecticide and Decis® 25CE (Deltamethrin) synthetic insecticide, at concentrations that do not cause clinical signs of maternal toxicity, could interfere in the histophysiology of the organs of neonate rats. Thirty-five pregnant albino rats, Rattus norvegicus albinus, were randomly distributed in seven groups: Group I received placebo (water); Groups II, III, and IV received 1.0, 10.0, and 20.0 mg of XenTari®/kg respectively; and Groups V, VI, and VII received 1.0, 2.0, and 4.0 mg of Deltamethrin/kg, respectively. The results showed that the highest doses of insecticides reduced the number of neonates. No histopathological alterations were observed in the kidneys, however, lipidosis, diffuse mononuclear inflammatory cells, and sinusoids congestion were observed in the liver. Rats from groups IV and VII presented atresia in the ovaries. Neonates from Group IV showed congestion and hemosiderin deposition in the testicle's blood vessels, which is characteristic of a process of hemolysis. In conclusion, both insecticides presented similar effects on organs and number of neonates born to rats exposed to sub-lethal doses that did not cause clinical symptoms of maternal intoxication.

El consumo anual actual de insecticidas en la agricultura en Brasil es más de tres millones de toneladas. Aproximadamente el 60% de los trabajadores rurales expuestos a los insecticidas son mujeres. La exposición ocurre a través de alimentos contaminados con desechos tóxicos y la absorción respiratoria y dérmica. El control biológico con Bacillus thuringiensis Berliner (Bt) ha adquirido una importancia creciente en la sustitución del uso de insecticidas convencionales. Sin embargo, las pruebas utilizadas para justificar la aprobación para el uso y la liberación del mercado de los productos Bt, y los protocolos utilizados para evaluar el desarrollo de toxicidad, son muy superficiales. Además, no se han realizado estudios que que permitan comparar los efectos entre hombres y mujeres y durante el embarazo y la lactancia. Por lo tanto, la hipótesis planteada en este estudio fue si la administración del Grupo de Trabajo XenTari ® (B. thuringiensis subsp. Aizawai) insecticida biológico y Decis ® 25CE (deltametrina) insecticidas sintéticos, en concentraciones que no causan signos clínicos de toxicidad materna, podría interferir en la histofisiología de los órganos de las ratas recién nacidas. Treinta y cinco ratas albinas preñadas, Rattus norvegicus albino, fueron distribuidas aleatoriamente en siete grupos: Grupo I recibió un placebo (agua), los Grupos II, III y IV recibieron 1,0, 10,0 y 20,0 mg de XenTari ® / kg, respectivamente, y Grupos V, VI y VII recibieron 1,0, 2,0 y 4,0 mg de deltametrina / kg, respectivamente. Los resultados mostraron que las dosis más altas de insecticidas redujeron el número de neonatos. No se observaron alteraciones histopatológicas en los riñones, sin embargo, se observaron en el hígado, lipidosis, difusas células inflamatorias mononucleares, y la congestión de sinusoides. Las ratas de los grupos IV y VII presentaron atresia ovárica. Los recién nacidos de grupo IV mostraron congestión y depósito de hemosiderina en los vasos sanguíneos del testículo, lo cual es característico de un proceso de hemólisis. En conclusión, los insecticidas presentaron efectos similares en los órganos y en el número de recién nacidos de ratas expuestas a dosis sub-letales, que no causan síntomas clínicos de toxicidad materna.