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Toxicological studies on medicinal plants are essential to ensure their safety and effectiveness in treating various diseases. Despite the species Chrysobalanus icaco L. being popularly used in the treatment of several diseases due to the pharmacological properties of its bioactive compounds, there are few studies in the literature regarding its toxicity regarding reproduction. Therefore, the purpose of this study was to assess the potential embryotoxic and teratogenic effects of the aqueous extract of C. icaco leaves (AECi) on Wistar rats. Animals were given AECi at doses of 100, 200, and 400 mg/kg during the pre-implantation and organogenesis periods. Data were analyzed using ANOVA followed by Tukey's test and Kruskal-Wallis. Pregnant rats treated during the pre-implantation period showed no signs of reproductive toxicity. Rats that received AECi at 100, 200, and 400 mg/kg during organogenesis did not exhibit any signs of maternal systemic toxicity or significant differences in gestational and embryotoxic parameters. Some skeletal changes were observed in the treated groups. Therefore, it can be suggested that AECi at doses of 100, 200, and 400 mg/kg is safe for treated animals and does not induce reproductive toxicity under the experimental conditions applied, but it also caused low systemic toxicity.
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Physical exercise is an important therapeutic agent for women with diabetes during gestation. However, its histophysiological consequences for the placenta remain unclear. In this study, we evaluated the expression of VEGF-A, IL1ß, TNFα, and type I collagen in the placentas of diabetic rats subjected to a swimming program. Thirty rats were divided into the following groups: CG, pregnant nondiabetic rats; CEG, nondiabetic pregnant rats subjected to swimming; DG, pregnant diabetic rats; DEG, pregnant diabetic rats subjected to swimming; DIG, pregnant diabetic rats treated with insulin; DIEG, pregnant diabetic rats treated with insulin and subjected to swimming. Diabetes was induced using streptozotocin [50 mg/kg intraperitoneally (i.p.)], and insulin was administered at a dose of 5 U/day i.p. (2 U at 10 am and 3 U at 7 pm) in the DIG group; in the DIEG group, insulin was administered at a dose of only 2 U/day at 7 pm. The rats were sacrificed on the 20th day of gestation. There was an increase in the expression of IL-1ß, TNF-α, VEGF-A, and type I collagen and a higher apoptotic index in the placentas of the DG and DEG groups, but there was a reduction in glycemia in the latter group. In the DIG and DIEG groups, the levels remained similar to those of the control; however, in these groups the reduction was more significant for all analyzed parameters. Therefore, in rats induced to diabetes during pregnancy, swimming, although reducing glycemic levels, did not prevent immunohistochemical changes in the placenta, suggesting the need for a multidisciplinary protocol associated with traditional pharmacological treatment.
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Diabetes Mellitus Experimental , Insulina , Animales , Apoptosis , Colágeno , Colágeno Tipo I , Citocinas , Diabetes Mellitus Experimental/tratamiento farmacológico , Diabetes Mellitus Experimental/metabolismo , Femenino , Humanos , Insulina/metabolismo , Placenta/metabolismo , Embarazo , Ratas , Ratas Wistar , Natación/fisiología , Factor de Necrosis Tumoral alfa , Factor A de Crecimiento Endotelial Vascular/uso terapéuticoRESUMEN
Chrysobalanus icaco L. is a native plant of Brazil used as a food source and traditionally for the treatment of various diseases. The aim of study was performed the phytochemical analysis by UPLC-DAD-ESI-QTOF-MS/MS, and evaluated acute and repeated dose oral toxicities of the C. icaco L. leaf aqueous extract (AECi). The acute toxicity study was performed using a dose of AECi 2000 mg/kg, while the repeated dose toxicity study, the AECi was administered daily at doses of 100, 200 and 400 mg/kg, for 28 days. Behavior and mortality of animals were observed during the test period and body weight, as well water and eating consumption. Hematological, biochemical parameters and histopathological examinations were carried out. Phytochemical analysis of the AECi revealed the presence of flavonoids and tannins. Oral single dose of 2000 mg/kg of AECi resulted in no mortalities or abnormal clinical signs. Studies of repeated dose toxicity promoted a reduction in the body weight of treated animals and an increase of hepatic enzymes alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in both, males and females. Histopathological analyzes showed alterations in the livers of animals treated with AECi. Thus, this study recommends the population take care when using this species, especially during prolonged periods.
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Peso Corporal/efectos de los fármacos , Chrysobalanaceae/química , Hígado/efectos de los fármacos , Fitoquímicos/toxicidad , Extractos Vegetales/toxicidad , Hojas de la Planta/química , Administración Oral , Animales , Femenino , Hígado/patología , Masculino , Medicina Tradicional , Ratones , Fitoquímicos/administración & dosificación , Extractos Vegetales/administración & dosificación , Pruebas de Toxicidad Aguda , Pruebas de Toxicidad Subaguda , Agua/químicaRESUMEN
The insecticide Match® (lufenuron), one of the main insect growth regulators used in pest control, has been presented as a viable alternative against the boll weevil, Anthonomus grandis (Coleoptera: Curculionidae), by inhibiting chitin synthesis. Thus, this study aimed to examine whether Match® interferes in the synthesis of the peritrophic matrix, leading to changes in the midgut epithelium, resulting in nutritional deficiency and reflecting, thereby, in the gametogenesis process of A. grandis. Floral cotton buds were immersed in the insecticide solution (800µL of Match®+200mL of distilled water) and offered to the adult insects. The midguts of the insects were evaluated after 24 and 120h after feeding. The gonads were evaluated after 120h. The results showed that Match®, in both evaluation periods, induced histopathological alterations such as disorganization, vacuolization and desquamation of the midgut epithelium; histochemical modifications in the distribution patterns of carbohydrates, although without quantitative changes; and a strong decrease in protein levels. No apoptosis were observed, however, there was an increase in the number of regenerative cell nests. In the testicles, a reduction in the amount of spermatozoids and reduced carbohydrate levels were observed, but no difference in protein levels. The ovarioles presented structural disorganization of follicular cells, yolk reduction and decrease in protein levels, however, no change in carbohydrates levels was noted. Therefore, it is concluded that Match® performs histopathologic and histochemical alterations in the midgut epithelium and the gonads of A. grandis adults, reflecting in the gametogenesis process, presenting itself as a promising tool in the management of this pest on cotton crops.
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Benzamidas , Sistema Digestivo/efectos de los fármacos , Gametogénesis/efectos de los fármacos , Insecticidas , Gorgojos/fisiología , Animales , Apoptosis/efectos de los fármacos , Sistema Digestivo/patología , Femenino , Inmunohistoquímica , Masculino , Ovario/efectos de los fármacos , Ovario/crecimiento & desarrollo , Ovario/patología , Testículo/efectos de los fármacos , Testículo/crecimiento & desarrollo , Testículo/patología , Gorgojos/crecimiento & desarrolloRESUMEN
PURPOSE: To describe the effects of melatonin associated with bacterial cellulose-based hydrogel on healing of skin wounds in diabetic rats. METHODS: Streptozotocin was used to induce diabetes in Wistar rats. After wound induction, animals were randomly divided into groups GC, GDCC, GDCB, and GDMCB. Animals were evaluated in days 3, 7, and 14 for the following variables: glycemic levels, histopathological and histochemical analyses, healing rate, morphometry and C-reactive protein. RESULTS: There was no change in glycemic levels in the diabetic animals as a result of the treatments; histopathological analyses showed better healing in GDCB and GDMCB groups, as well as histochemistry; at day 14, the highest healing rate was observed in animals from the GDMCB group, reaching almost 100%; morphometry revealed a significant increase of fibroblasts and reduction of macrophages and blood vessels in lesions treated with bacterial cellulose associated or not with melatonin when compared to the other experimental groups. There was also an increase in C-reactive protein in GDCC group at day 14. CONCLUSION: Bacterial cellulose-based dressings associated with systemic melatonin showed beneficial results in experimentally induced wounds in diabetic rats, favoring the healing process.
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Celulosa , Diabetes Mellitus Experimental , Melatonina , Ratas Wistar , Piel , Cicatrización de Heridas , Animales , Melatonina/uso terapéutico , Melatonina/farmacología , Cicatrización de Heridas/efectos de los fármacos , Diabetes Mellitus Experimental/complicaciones , Celulosa/uso terapéutico , Celulosa/farmacología , Masculino , Piel/efectos de los fármacos , Piel/lesiones , Piel/patología , Hidrogeles/uso terapéutico , Distribución Aleatoria , Ratas , Proteína C-Reactiva/análisis , Factores de Tiempo , Reproducibilidad de los Resultados , Glucemia/análisis , Glucemia/efectos de los fármacos , Antioxidantes/uso terapéutico , Antioxidantes/farmacologíaRESUMEN
We investigated the effects of B. thuringiensis-based biological insecticides, XenTari and Dipel, and deltamethrin on the reproductive development of pups of pregnant rats. Twenty 90-day-old pregnant rats were divided randomly onto four equal groups: control group (GC) administered only water; XenTari group (GX) administered 1 mg XenTari (containing Cry1Ac toxin of B. thuringiensis)/100 g body weight; Dipel group (GDi) administered 1 mg Dipel (containing Cry1Aa, Cry1Ab and Cry1Ac toxins of B. thuringiensis)/100 g body weight; and a deltamethrin group (GDe) administered 2 mg deltamethrin (0.08 ml Keshet 25EC)/kg body weight as a positive control. Insecticides were administered by gavage at doses of 1 mg/100 g/day (GX and GDi), and 2 mg/kg/day (GDe) during pregnancy and lactation. Treatment with both biologic and synthetic insecticides reduced the weight gain of the mothers. The biological insecticides reduced the number, weight and length, and increased malformation and mortality of the offspring. In female offspring for all three groups administered insecticides, opening of the vagina was delayed, metestrus was increased and estrogen and progesterone levels were reduced compared to proestrus, estrus and metestrus of the cycle. The ovaries of female offspring of all three groups administered insecticides contained numerous tertiary and atretic follicles, few corpora lutea, primary and secondary follicles, and reduced estrogen receptors compared to controls. In male offspring, all three groups exposed to insecticides exhibited reduced testosterone levels. Histopathological changes in the testes including vacuolation and desquamation of the seminiferous epithelium were observed only in the GX and GDi groups. The number of androgen receptors was reduced significantly in the testes and testicular morphometry revealed reduced tubule diameter, height of the seminiferous epithelium and total tubule length compared to the control. The biological insecticides, XenTari and Dipel, administered in sublethal doses to pregnant rats, caused reproductive changes in the offspring similar to those of the insecticide, deltamethrin.
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Bacillus thuringiensis , Insecticidas , Piretrinas , Embarazo , Ratas , Masculino , Femenino , Animales , Insecticidas/toxicidad , Piretrinas/toxicidad , Peso CorporalRESUMEN
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.
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Diabetes Mellitus Experimental , Diabetes Gestacional , Melatonina , Animales , Diabetes Mellitus Experimental/tratamiento farmacológico , Diabetes Gestacional/prevención & control , Femenino , Feto , Humanos , Melatonina/farmacología , Melatonina/uso terapéutico , Placenta , Embarazo , RatasRESUMEN
Exposure to the herbicides Paraquat and Roundup® may cause cell lesions due to an increase in oxidative stress levels in different biological systems, even in the liver. The aim of this study was to analyze the effect of melatonin on liver of rats exposed to herbicides. A total of 35 rats were randomly divided into seven equal-sized groups: control, Paraquat, Roundup®, Paraquat + Roundup®, Paraquat + melatonin, Roundup® + melatonin, and Paraquat + Roundup® + melatonin. Samples of blood and hepatic tissue were collected at the end of the seventh day of exposure and treatment with melatonin. Body weight, hematological parameters, and histopathological, biochemical analyses and determination of oxidative stress levels in liver were evaluated. Body weight was compromised (P < 0.01). Alterations of hematologic parameters were significant when compared to control (P < 0.001). Biochemically, serum levels of albumin decreased (P < 0.001), but serum levels of alanine aminotransferase, aspartate aminotransferase, and alkaline phosphatase increased (P < 0.001). Histopathology revealed necrotic hepatocytes, portal and central-lobular inflammatory infiltrate, congestion of capillaries. Serum levels of thiobarbituric acid reactive substances were found to be significantly elevated (P < 0.05; P < 0.001), and serum level of reduced glutathione was significantly lower (P < 0.05; P < 0.001). The groups treated concomitantly with melatonin revealed results similar to those of the control. However, melatonin acted as a protective agent for the liver against experimentally induced hepatic toxicity, promoting prevention of body weight, oxidative stress, and normalization of hematological and biochemical parameters.
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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.
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Fibra de Algodón/parasitología , Insecticidas/farmacología , Mariposas Nocturnas/fisiología , Aceites Volátiles/farmacología , Control de Plagas , Animales , Femenino , Insecticidas/química , Aceites Volátiles/química , Reproducción/efectos de los fármacosRESUMEN
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.
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Toxinas de Bacillus thuringiensis/toxicidad , Endotoxinas/toxicidad , Proteínas Hemolisinas/toxicidad , Insecticidas/toxicidad , Riñón , Lactancia/metabolismo , Hígado , Exposición Materna/efectos adversos , Efectos Tardíos de la Exposición Prenatal , Animales , Femenino , Riñón/crecimiento & desarrollo , Riñón/patología , Hígado/crecimiento & desarrollo , Hígado/patología , Embarazo , Efectos Tardíos de la Exposición Prenatal/inducido químicamente , Efectos Tardíos de la Exposición Prenatal/metabolismo , Efectos Tardíos de la Exposición Prenatal/patología , Ratas , Ratas WistarRESUMEN
We evaluated the evidence in research on the effects of melatonin on hypothyroidism and gonadal development. According to the World Health Organization, thyroid disorders due to iodine deficiency affect about 740 million people worldwide. Hypothyroidism is a thyroid dysfunction characterized by hypometabolism of the gland, with reduced or physiologically normal T3 and T4 serum levels, and high TSH level. This disorder occurs mainly in adult women in the reproductive phase, with a prevalence of 2% among the world's female population, with profound repercussions on gestation and fetal formation. During the gestational period, the thyroid is initially stimulated by high concentrations of human chorionic gonadotrophin; thus, maintaining maternal euthyroidism during pregnancy and lactation is fundamental for fetal growth and development. Besides, the hormones produced by this gland are involved in the formation of various organs, such as the skin, brain and gonads. Hypothyroidism is associated with several menstrual abnormalities, anovulation and hyperprolactinemia, resulting in a high rate of abortions, premature births, placental rupture, and weight-related neonatal deficits. In addition, there are studies showing that hypothyroidism can affect ovarian morphology (number of ovarian follicles) and testicular morphology (changes in the testicular-lumen epithelium). Melatonin is a hormone known to modulate the estrous cycle and pregnancy, and studies show that the exogenous application of melatonin increased T4 levels in female rats and controlled the decrease in T3 serum levels, reverting the sigs of hypothyroidism.
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Hipotiroidismo/tratamiento farmacológico , Melatonina/uso terapéutico , Ovario/efectos de los fármacos , Testículo/efectos de los fármacos , Animales , Femenino , Masculino , Melatonina/farmacología , Ovario/crecimiento & desarrollo , Ratas , Testículo/crecimiento & desarrolloRESUMEN
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.
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Gónadas/efectos de los fármacos , Hipotiroidismo/inducido químicamente , Melatonina/farmacología , Complicaciones del Embarazo/inducido químicamente , Glándula Tiroides/efectos de los fármacos , Animales , Antioxidantes/farmacología , Antitiroideos/toxicidad , Femenino , Gónadas/crecimiento & desarrollo , Embarazo , Efectos Tardíos de la Exposición Prenatal , Propiltiouracilo/toxicidad , Ratas , Glándula Tiroides/crecimiento & desarrolloRESUMEN
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 10â¯mg/kg in drinking water every day for 20 days at night. Diabetes was induced by streptozotocin (60â¯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.
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Antioxidantes/farmacología , Diabetes Mellitus Experimental/tratamiento farmacológico , Melatonina/farmacología , Testículo/efectos de los fármacos , Animales , Peso Corporal/efectos de los fármacos , Diabetes Mellitus Experimental/sangre , Peroxidación de Lípido/efectos de los fármacos , Masculino , Estrés Oxidativo/efectos de los fármacos , Ratas Wistar , Estreptozocina/farmacologíaRESUMEN
Metronidazole is an antiprotozoal and antibacterial used in gynecology and obstetrics for the treatment of parasitic infections. However, despite having clinical use for more than three decades, questions about the safety of its use during pregnancy is not well understood. Thus, the present study evaluated the effect of metronidazole on placental and fetal development in pregnant rats. Metronidazole was orally administered by gavage at a dosage of 130 mg/kg for 7 and 14 days. Morphological analysis, morphometry and immunohistochemistry were performed at the implantation sites and placentas with 14 days of development. The results showed that in the treated group there was a significant reduction in the number of implantation sites, total placental disc area and constituent elements of the labyrinth and spongiotrophoblast layers. Histochemical analysis revealed no significant changes in the content of collagen, elastic and reticular fibers. The TUNEL test showed apoptotic activity in the implantation sites and placentas with 14 days of development independent of the treatment. There was no evidence of malformation in the neonates. However, there was a significant reduction in the number and weight of neonates in the group treated with metronidazole when compared to the control group. Thus, it is concluded that the administration of 130 mg/kg of metronidazole during pregnancy in rats, in addition to interfering with the number of implanted embryos, promotes changes in placental structure and interferes with fetal development. This suggests that this drug should be used with caution during pregnancy.
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INTRODUCTION: Pomacea lineata acts as the natural biological controller of Biomphalaria glabrata, the intermediate host of Schistosoma mansoni, as they are found in the same environment. However, there are no studies reporting an infection in P. lineata due to S. mansoni. Thus, this work investigated parameters related to the immunity of P. lineata after exposure for 24 and 48 h to S. mansoni under experimental conditions. METHODS: The F1 generation of these snails was used in this study. The total and differential counts of hemocytes, phenoloxidase, nitric oxide, total proteins, expression of TNF-α in hemocytes and histopathology of the head-foot organ were analyzed. RESULTS: Exposure to S. mansoni promoted an increase in the total number of hemocytes, an increase of granulocytes, a reduction of agranulocytes and hyalinocytes, an increase in phenoloxidase levels, total proteins and nitric oxide. There was TNF-α expression in the agranulocytes and granulocytes, increasing in intensity after exposure to the trematode. Head-foot histopathology revealed the presence of sporocytes in the fibromuscular layer surrounded by granulation tissue only within 24 h. At 48 h, there was marked fibrosis in this layer and little granulation tissue. CONCLUSION: Thus, we can conclude that P. lineata seems to trigger a series of immunological strategies in a very effective way that confers some resistance to S. mansoni.
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Resistencia a la Enfermedad , Gastrópodos/inmunología , Schistosoma mansoni/inmunología , Esquistosomiasis mansoni/veterinaria , Animales , Hemocitos/inmunología , Inmunohistoquímica , Modelos Animales , Monofenol Monooxigenasa/análisis , Óxido Nítrico/análisis , Esquistosomiasis mansoni/patología , Factor de Necrosis Tumoral alfa/análisisRESUMEN
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 (3â¯g/kg/day); ET+10â¯M - Rats receiving ethanol (3â¯g/kg/day) and melatonin (10â¯mg/kg/day); ET+15â¯M - Rats receiving ethanol (3â¯g/kg/day) and melatonin (15â¯mg/kg/day); PC - Positive control (40â¯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 15â¯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.
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Depresores del Sistema Nervioso Central/toxicidad , Daño del ADN , Etanol/toxicidad , Trastornos del Espectro Alcohólico Fetal/prevención & control , Melatonina/farmacología , Fármacos Neuroprotectores/farmacología , Efectos Tardíos de la Exposición Prenatal/prevención & control , Animales , Animales Recién Nacidos , Encéfalo/efectos de los fármacos , Ensayo Cometa , Femenino , Trastornos del Espectro Alcohólico Fetal/etiología , Hígado/efectos de los fármacos , Masculino , Pruebas de Micronúcleos , Embarazo , Efectos Tardíos de la Exposición Prenatal/inducido químicamente , Ratas , Ratas WistarRESUMEN
Exposure to the herbicides Paraquat (PQ) and Roundup® may cause cell lesions due to an increase in oxidative stress levels in different biological systems, even in the reproductive system. OBJECTIVE: Evaluate the possible changes in reproductive parameters and hepatic, as well as its prevention by simultaneous application of melatonin. METHODS: Thirty-five female rats at the age of 3 months were divided into seven groups: three groups exposed to sub-lethal doses of the herbicides PQ (50mg/kg) and Roundup® (500mg/kg) (n=5, G2, G3 and G4); three groups exposed to herbicides and simultaneous treatment with 10mg/kg of Melatonin (n=5, G5, G6 and G7) and control group (n=5, G1) from the first to the seventh day of pregnancy. On the seventh day of pregnancy, the rats were anesthetized and euthanized, followed by laparotomy to remove their reproductive tissues and liver. Body and ovary weights were taken and the number of implantation sites, corpora lutea, preimplantation losses, implantation rates were counted and histopathology of the implantation sites, morphometry of the surface and glandular epithelia of endometrium and hepatic oxidative stress were undertaken. RESULTS: The present study shows the decrease in body and ovary weight, decrease in the number of implantation sites, implantation rate, in the total number of corpora lutea and increase of preimplantation percentages were observed when compared to the G1: Fig. 1 and Table 1, (p>0.001 ANOVA/Tukey). The histopathological analysis of the implantation sites showed a disorder of the cytotrophoblast and cell degeneration within the blastocyst cavity in Fig. 4. Morphometry revealed a reduction in surface and glandular epithelia and in the diameter of the endometrial glands (Table 2; p>0.05 ANOVA/Tukey), whereas in liver, serum levels of thiobarbituric acid reactive substances (TBARS) were found to be significantly elevated (Fig. 2; p>0.001; p>0.05 ANOVA/Tukey), and serum level of reduced glutathione (GSH) was significantly lower (Fig. 3; p>0.001 ANOVA/Tukey). However, treatments with melatonin exhibited improvements in reproductive parameters, as well as reduced lesions in the implantation sites (Fig. 4.) and in serum levels TBARS (Fig. 2; p>0.001 ANOVA/Tukey), serum levels GSH (Fig. 3; p>0.001; p>0.05 ANOVA/Tukey). CONCLUSIONS: These results reveal that melatonin is a protective agent against experimentally induced maternal/embryo toxicity with herbicides and favoring normalization of reproductive parameters and hepatic.
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Exposición a Riesgos Ambientales , Herbicidas/toxicidad , Melatonina/farmacología , Embarazo/efectos de los fármacos , Sustancias Protectoras/farmacología , Animales , Peso Corporal/efectos de los fármacos , Femenino , Glicina/análogos & derivados , Glicina/toxicidad , Peroxidación de Lípido/efectos de los fármacos , Tamaño de los Órganos/efectos de los fármacos , Ratas , GlifosatoRESUMEN
AIM: To evaluate the therapeutic effects of bone marrow-derived CD11b+CD14+ monocytes in a murine model of chronic liver damage. METHODS: Chronic liver damage was induced in C57BL/6 mice by administration of carbon tetrachloride and ethanol for 6 mo. Bone marrow-derived monocytes isolated by immunomagnetic separation were used for therapy. The cell transplantation effects were evaluated by morphometry, biochemical assessment, immunohistochemistry and enzyme-linked immunosorbent assay. RESULTS: CD11b+CD14+ monocyte therapy significantly reduced liver fibrosis and increased hepatic glutathione levels. Levels of pro-inflammatory cytokines, including tumor necrosis factor-α, interleukin (IL)-6 and IL-1ß, in addition to pro-fibrotic factors, such as IL-13, transforming growth factor-ß1 and tissue inhibitor of metalloproteinase-1 also decreased, while IL-10 and matrix metalloproteinase-9 increased in the monocyte-treated group. CD11b+CD14+ monocyte transplantation caused significant changes in the hepatic expression of α-smooth muscle actin and osteopontin. CONCLUSION: Monocyte therapy is capable of bringing about improvement of liver fibrosis by reducing oxidative stress and inflammation, as well as increasing anti-fibrogenic factors.
Asunto(s)
Tratamiento Basado en Trasplante de Células y Tejidos/métodos , Citocinas/metabolismo , Cirrosis Hepática/terapia , Hígado/metabolismo , Monocitos/trasplante , Actinas/metabolismo , Animales , Antígeno CD11b/metabolismo , Tetracloruro de Carbono/toxicidad , Separación Celular , Modelos Animales de Enfermedad , Ensayo de Inmunoadsorción Enzimática , Etanol/toxicidad , Citometría de Flujo , Glutatión/metabolismo , Humanos , Inmunohistoquímica , Receptores de Lipopolisacáridos/metabolismo , Hígado/patología , Cirrosis Hepática/inducido químicamente , Cirrosis Hepática/patología , Masculino , Ratones , Ratones Endogámicos C57BL , Monocitos/metabolismo , Osteopontina/metabolismo , Estrés OxidativoRESUMEN
Spodoptera frugiperda is the principal corn pest in Brazil. Searches for new control methods that minimize the adverse effects of synthetic insecticides have initiated a resurgence of the use of botanical insecticides. Citronella oil (a product of Cymbopogon winterianus) is an effective repellent and insecticide. Thus, biochemical profile changes in oil-treated larvae and its influence on reproduction were assessed. Corn leaves dipped in a 50mg/mL concentration were offered to third instar larvae for 24h and assessed in sixth instar to estimate protein, lipid, sugar, and glycogen levels. Adult testes and ovarioles were collected for histological and histochemical analysis 24h after emergence. Number of eggs and hatching rate were also measured. Oil-treated larvae showed an increase in glycogen and a decrease in protein, lipid, and totals sugar content. Control testes exhibited connective tissue lining and cysts with abundant spermatozoids. However, intense peripheral vacuolation and neutral carbohydrates reduction occurred in oil-treated individuals. Control ovarioles showed normal morphologic characteristics. On the other hand, oil-treatment ovarioles showed follicular cell stratification and removal, reduced nurse cell development, reduced yolk quantity, a thinner conjunctiva sheath, and a reduction in proteins and neutral carbohydrates. Eggs derived from oil-treated pairs were unviable. Therefore, sub-lethal doses of citronella oil alters the biochemical profile of S. frugiperda larvae, causing damage to their reproductive histophysiology and results in diminished reproduction or reproductive failure.
Asunto(s)
Insecticidas/farmacología , Aceites de Plantas/farmacología , Spodoptera/fisiología , Animales , Femenino , Larva/citología , Larva/efectos de los fármacos , Masculino , Ovario/citología , Ovario/efectos de los fármacos , Reproducción , Spodoptera/citología , Spodoptera/efectos de los fármacos , Testículo/citología , Testículo/efectos de los fármacosRESUMEN
The pineal gland is responsible for producing a hormone called melatonin (MEL), and is accepted as the gland that regulates reproduction in mammals. Prolactin (PRL) also exhibits reproductive activity in animals in response to photoperiod. It is known that the concentrations of PRL are high in the summer and reduced during winter, the opposite of what is seen with melatonin in these seasons. In placental mammals, both prolactin and melatonin affect implantation, which is considered a critical point of pregnancy, since a successful pregnancy requires the development of a synchronous interaction between the endometrium and blastocyst for placental development. It is also known that PRL levels during pregnancy are essential for the maintenance of pregnancy, because this hormone induces the corpus luteum to produce progesterone, in addition to stimulating blastocyst implantation to maintain pregnancy and form the placenta. However, melatonin levels in plasma have also been shown to increase during pregnancy, peaking at the end of this period, which suggests that this hormone plays an important role in the maintenance of pregnancy. Thus, it is clear that treatment with prolactin or melatonin interferes with the processes responsible for the development and maintenance of pregnancy.