A low dose of benzo(a)pyrene during prepuberty in male rats generated immediate oxidative stress in the testes and compromised steroidogenic enzymes/proteins.

The prepubertal period is crucial for sexual development and any alterations can interfere with the reproductive system in adulthood. The aim of this study was to evaluate how Benzo(a)pyrene (BaP) can affect the testes during the prepubertal period. Juvenile male Wistar rats were divided into a control (corn oil + DMSO) and a BaP-group (0.1 µg/kg/day), exposed to BaP for 31 days (gavage), and all parameters were evaluated on postnatal day (PND) 54. Leukocyte counts were decreased. Histological analyses of the testes revealed that height and seminiferous tubules diameters (STDs) were reduced, tubular dynamics were altered, and Leydig cell atrophy was evident in the BaP-group. The testosterone concentration was decreased while FSH levels increased within the BaP-exposed group. Steroidogenic enzymes in the testes were decreased, but steroidogenic acute regulatory protein was not altered. The expression of gstp1 and ckit enzymes was decreased. Reduced glutathione (GSH) and superoxide dismutase (SOD) were increased, whereas malondialdehyde (MDA) was decreased in the testes. In conclusion, BaP or its metabolites causes low systemic toxicity; however, it adversely influences testicular function by disrupting the hormonal axis, unbalancing testicular antioxidative, and blocking the action of the steroidogenic mechanisms.

Antidiabetic, cytotoxic and antioxidant activities of oil extracted from Acrocomia aculeata pulp.

This study evaluated the hypoglycemic effect of the oil extracted from the Acrocomia aculeata pulp (OPAC) in normoglycemic rats and streptozotocin (STZ), fructose-induced diabetic rat models and its in vitro antioxidant and cytotoxic potential. OPAC (3, 30 or 300 mg/kg, v.o.) significantly decreased (p < 0.05) the high glucose levels induced by a high fructose-diet in rats. Persistent treatment with OPAC for 24 days also reduced the high plasmatic glucose induced by STZ. In normoglycemic animals, OPAC significantly decreased glucose levels. While A. aculeata oil exhibited good in vitro antioxidant activity, no sign of cytotoxicity was observed in LLC-PK1 cells (5-500 µg/mL). OPAC has antidiabetic and antioxidant activities without causing in vitro cytotoxicity.

In vitro antifungal activity of Myracrodruon urundeuva Allemão against human vaginal Candida species.

Myracrodruon urundeuva is a plant native to Brazil, which is used by the indigenous population for the treatment of candidiasis. The aims of this study were to evaluate the antifungal activity of extract against human vaginal Candida species and evaluate the possible toxicological activities of M. urundeuva. Initially, ethanol extracts, ethyl acetate fractions, and hydroalcoholic fractions of the bark and leaf of M. urundeuva were used to determine the minimum inhibitory concentration. The extracts that showed antifungal activity were characterized by liquid chromatography and subjected to toxicity assessment. Toxic, cytotoxic, genotoxic, and mutagenic testing were performed using Allium cepa and Ames assays with the ethanol extracts of the bark and leaves. Hemolytic activity was evaluated in erythrocytes and acute toxicity in rats. The ethanol bark extracts showed best activity against Candida albicans, C. krusei, and C. tropicalis ATCC (4-512 µg/mL). Chemical characterization indicated the presence of flavonoids and tannins in the extracts. Hemolytic activity, genotoxicity, and mutagenicity were not observed. The results of the Ames and A. cepa tests were also in agreement, ethanol bark extracts and ethanol leaf extracts of M. urundeuva showed absence of mutagenic activity. Similar results were observed in the A. cepa assay and acute toxicity test in rats. M. urundeuva bark extracts showed potential for the treatment of vaginal infections caused Candida species, as a topical.

Toxicological analysis and antihyperalgesic, antidepressant, and anti-inflammatory effects of Campomanesia adamantium fruit barks.

OBJECTIVE: This study evaluates the anti-inflammatory, antihyperalgesic, and antidepressive potential of the hydroalcoholic extract of Campomanesia adamantium fruit barks (CAE) on rodents and determines the safety of this plant. METHODS: The acute toxicity of CAE was evaluated by oral administration to female rats as single doses of 0, 500, 1000, or 2000 mg/kg body weight. General behavior and toxic symptoms were observed for 14 days. In the subacute toxicity test, male and female rats received 125 or 250 mg/kg body weight of CAE for 28 days. The oral anti-inflammatory activity of CAE was evaluated in carrageenan-induced pleurisy in male mice. The effect of treatment with CAE (100 mg/kg) for 15 days was evaluated in mechanical hyperalgesia (electronic von Frey), depressive behavior (forced swimming test), and cold hypersensitivity in spared nerve injury (SNI) model in rats. RESULTS: No clinical signs of toxicity were observed in animals from the experimental groups during acute and subacute exposure to CAE. At pleurisy test, the oral administration of CAE significantly inhibited leukocyte migration and protein leakage at all doses tested when compared to control. Oral administration of CAE for 3-15 days significantly inhibited SNI-induced mechanical hyperalgesia and increased immobility in the forced swim test. Finally, on the 15th day, oral treatment with CAE prevented the increase in sensitivity to a cold stimulus induced by SNI. DISCUSSION: The present study shows that C. adamantium extract has anti-inflammatory, antihyperalgesic, and antidepressive properties in rodents without causing toxicity.

Perinatal exposure to insecticide fipronil: effects on the reproductive system in male rats.

Fipronil is an insecticide widely used in agriculture, veterinary medicine and public health that has recently been listed as a potential endocrine disrupter. In the present study we evaluated the effects of perinatal exposure to fipronil during the period of sexual brain differentiation and its later repercussions on reproductive parameters in male rats. Pregnant rats were exposed (via gavage) to fipronil (0.03, 0.3 or 3mgkg-1) from Gestational Day 15 until Postnatal Day 7. Fipronil exposure did not compromise the onset of puberty. In adulthood, there was no effect on organ weight or sperm production. Furthermore, there were no adverse effects on the number of Sertoli cells per seminiferous tubule, testicular and epididymal histomorphometry or histopathology or expression patterns of androgen receptor in the testis. Similarly, no changes were observed in the sexual behaviour or hormone levels. However, in rats exposed to fipronil, changes in sperm motility were observed, with a decrease in motile spermatozoa and an increase in non-mobile spermatozoa, which can compromise sperm quality in these rats. Perinatal exposure to fipronil has long-term effects on sperm parameters, and the epididymis can be a target organ. Additional studies should be undertaken to identify the mechanisms by which fipronil affects sperm motility.

In vitro antifungal activity of Myracrodruon urundeuva Allemão against human vaginal Candida species

ABSTRACT Myracrodruon urundeuva is a plant native to Brazil, which is used by the indigenous population for the treatment of candidiasis. The aims of this study were to evaluate the antifungal activity of extract against human vaginal Candida species and evaluate the possible toxicological activities of M. urundeuva. Initially, ethanol extracts, ethyl acetate fractions, and hydroalcoholic fractions of the bark and leaf of M. urundeuva were used to determine the minimum inhibitory concentration. The extracts that showed antifungal activity were characterized by liquid chromatography and subjected to toxicity assessment. Toxic, cytotoxic, genotoxic, and mutagenic testing were performed using Allium cepa and Ames assays with the ethanol extracts of the bark and leaves. Hemolytic activity was evaluated in erythrocytes and acute toxicity in rats. The ethanol bark extracts showed best activity against Candida albicans, C. krusei, and C. tropicalis ATCC (4-512 µg/mL). Chemical characterization indicated the presence of flavonoids and tannins in the extracts. Hemolytic activity, genotoxicity, and mutagenicity were not observed. The results of the Ames and A. cepa tests were also in agreement, ethanol bark extracts and ethanol leaf extracts of M. urundeuva showed absence of mutagenic activity. Similar results were observed in the A. cepa assay and acute toxicity test in rats. M. urundeuva bark extracts showed potential for the treatment of vaginal infections caused Candida species, as a topical.

Glutamate-induced obesity leads to decreased sperm reserves and acceleration of transit time in the epididymis of adult male rats.

BACKGROUND: Given the established fact that obesity interferes with male reproductive functions, the present study aimed to evaluate sperm production in the testis and storage in the epididymis in a glutamate-induced model of obesity. METHODS: Male rats were treated neonatally with monosodium glutamate (MSG) at doses of 4 mg/kg subcutaneously, or with saline solution (control group), on postnatal days 2, 4, 6, 8 and 10. On day 120, obesity was confirmed by the Lee index in all MSG-treated rats. After this, all animals from the two experimental groups were anesthetized and killed to evaluate body and reproductive organ weights, sperm parameters, plasma hormone levels (FSH, LH and testosterone), testicular and epididymal histo-morphometry and histopathology. RESULTS: Significant reductions in absolute and relative weights of testis, epididymis, prostate and seminal vesicle were noted in MSG-treated animals. In these same animals plasma testosterone and follicle-stimulating hormone (FSH) concentrations were decreased, as well as sperm counts in the testis and epididymis and seminiferous epithelium height and tubular diameter. The sperm transit time was accelerated in obese rats. However, the number of Sertoli cells per seminiferous tubule and stereological findings on the epididymis were not markedly changed by obesity. CONCLUSIONS: Neonatal MSG-administered model of obesity lowers sperm production and leads to a reduction in sperm storage in the epididymis of adult male rats. The acceleration of sperm transit time can have implications for the sperm quality of these rats.

Effects of diuron on male rat reproductive organs: a developmental and postnatal study.

This study was performed to determine whether developmental exposure (perinatal and juvenile) to the herbicide diuron exerted adverse effects on adult rat male reproductive system. Pregnant Sprague-Dawley rats received basal diet or diet containing diuron at 500 or 750 ppm from gestational day 12 (GD 12) until the end of lactation period (postnatal day 21, PND 21). After weaning male offspring received basal diet or diet containing diuron until PND 42 (peripubertal age). At PND 90, adult male rats from each experimental group were anesthetized and euthanized for evaluation of body and reproductive organ weights, sperm parameters, plasma testosterone levels, and testicular and epididymal histopathology. Male offspring exposed to diuron at 750 ppm displayed reduced body weight at PND 10, 21, 42, and 90 compared to controls. At PND 90, diuron treatment did not induce significant change in daily sperm production, sperm morphology and motility, and testosterone levels compared to controls. In conclusion, diuron at 750 ppm induced male offspring toxicity but these alterations were not permanent, as evidenced by absence of reproductive-system alterations in adult Sprague Dawley rats.

Effects of gestational and lactational fenvalerate exposure on immune and reproductive systems of male rats.

The aim of this study was to determine the consequent reproductive developmental and immunotoxic effects due to exposure to fenvalerate during pregnancy and lactation in male offspring of maternal-treated rats. Pregnant rats were treated daily by oral gavage with 40 or 80 mg/kg of fenvalerate or corn oil (vehicle, control), from d 12 of pregnancy to d 21 of lactation. Immune and reproductive developmental effects were assessed in male offspring at postnatal days (PND) 40 (peripuberty), 60 (postpuberty), and 90 (sexual maturity). Treatment with the higher dose (80 mg/kg) resulted in convulsive behavior, hyperexcitability, and mortality in 45% of the dams. Fenvalerate was detected in the fetus due to placental transfer, as well as in pups due to breast-milk ingestion, persisting in male offspring until PND 40 even though pesticide treatment was terminated on PND 20. However, fenvalerate did not produce marked alterations in age of testicular descent to the scrotum and prepucial separation, parameters indicative of puberty initiation. In contrast, at puberty, there was a reduction in testicular weight and sperm production in male offspring of maternal-treated rats. At adulthood, the sperm counts and fertility did not differ between control and treated groups. Testosterone levels were not changed at any time during reproductive development. Similarly, no apparent exposure-related effects were detected in the histological structures of the lymphohematopoietic system. Data indicate that fenvalerate, in this experimental model, interfered with initial development of the male reproductive system, but that these effects on sperm production or fertility did not persist into adulthood. There was no apparent evidence that fenvalerate altered testosterone levels or produced a disruption in male endocrine functions.

Fenvalerate, a pyrethroid insecticide, adversely affects sperm production and storage in male rats.

The aim of this study was to investigate the potential estrogenic activity of fenvalerate by examining reproductive and fertility capabilities in Wistar rats. Adult male animals were treated for 30 d with 20 or 40 mg/kg/d fenvalerate or corn oil (vehicle) by oral gavage. Further, a possible estrogenic activity of fenvalerate (0.4, 1, 4, 8, or 40 mg/kg) was tested after a 3-d treatment of immature female rats using the uterotrophic assay. Exposure to the higher dose of fenvalerate was toxic to testis and epididymis as shown by a decrease in the absolute weights and sperm counts in both organs. Although the sperm counts were reduced, the fertility and sexual behavior were similar in control rats and rats treated with 40 mg/kg pesticide. Fenvalerate did not exert estrogenic activity in vivo at the tested doses. Data suggest that fenvalerate treatment in this study failed to compromise fertility, possibly due to enhanced reproductive capacity in rodents compared to humans.

Reproductive effects in male rats exposed to diuron.

Diuron is a ureic herbicide considered to have very low toxicity. The present study evaluated several aspects of reproductive toxicity of diuron in adult male rats. Diuron was diluted in corn oil and administered by oral gavage to groups of 18-20 rats at doses of 0, 125 or 250 mg/kg per day for 30 days; the control group received only the corn oil vehicle. At the end of the treatment period, approximately half the animals from each group were assigned to one of two terminal assessment lines: (1) reproductive organ, liver and kidney weights; measurement of diuron concentrations in liver and kidney; plasma testosterone determinations; evaluation of daily sperm production per testis; sperm number and sperm transit time in the epididymis; or (2) sexual behavior assessment during cohabitation with a receptive female; fertility and pregnancy outcome after natural mating; testicular, epididymal, kidney and liver histopathology; sperm morphology. After 30 days of oral diuron treatment, there were no treatment-related changes in body weights, but dose-related diuron residues were detected in the liver of all treated rats and absolute and relative liver weights were increased in both groups. There were no statistically significant differences between the treated and control groups obtained in plasma testosterone concentrations, or in parameters of daily sperm production, sperm reserves in the epididymis, sperm morphology or measured components of male sexual behavior. On the other hand, the number of fetuses in the litters from diuron-treated rats was slightly smaller than litters from control rats. Therefore, although the results did not indicate that diuron exposure resulted in direct male reproductive toxicity in the rat, they suggest that additional studies should be undertaken to investigate the possible effects on fertility and reproductive performance.

Effects of prenatal hydrocortisone acetate exposure on fertility and sexual behavior in male rats.

The aim of the present study was to investigate the effects of hydrocortisone during the prenatal period and its later repercussions on the fertility and sexual behavior of male rats. Pregnant rats were treated (s.c.) with hydrocortisone acetate, at 1.5 mg/day on the 17th, 18th, and 19th days of gestation. Decreased body weight and no alteration in anogenital distance were observed in male offspring. Adulthood, presented reductions of body weight, plasma testosterone levels, and seminal-vesicle wet weight without secretion as well as no alteration in the wet weights of the testes, epididymis, and seminal vesicle with secretion in the treated group. Males exposed to hydrocortisone during the prenatal period were able to mate with normal females, which became pregnant but exhibited an increased number of post-implantation losses. In spite of this, these treated males exhibited decreased male sexual behavior and the appearance of female sexual behavior after these male rats were castrated and pretreated with exogenous estrogen. These results indicate that exposure to hydrocortisone in the later stages of pregnancy may have a long-term effect on the fertility and sexual behavior of male rats, suggesting an incomplete masculinization and defeminization of the central nervous system.