RESUMO
Lisdexamfetamine dimesylate (LDX) is a prodrug of dextroamphetamine, which has been widely recommended for the treatment of Attention-Deficit/Hyperactivity Disorder (ADHD). There are still no data in the literature relating the possible toxic effects of LDX in the kidney. Therefore, the present study aims to evaluate the effects of LDX exposure on morphological, oxidative stress, cell death and inflammation parameters in the kidneys of male pubertal Wistar rats, since the kidneys are organs related to the excretion of most drugs. For this, twenty male Wistar rats were distributed randomly into two experimental groups: LDX group-received 11,3 mg/kg/day of LDX; and Control group-received tap water. Animals were treated by gavage from postnatal day (PND) 25 to 65. At PND 66, plasma was collected to the biochemical dosage, and the kidneys were collected for determinations of the inflammatory profile, oxidative status, cell death, and for histochemical, and morphometric analyses. Our results show that there was an increase in the number of cells marked for cell death, and a reduction of proximal and distal convoluted tubules mean diameter in the group that received LDX. In addition, our results also showed an increase in MPO and NAG activity, indicating an inflammatory response. The oxidative status showed that the antioxidant system is working undisrupted and avoiding oxidative stress. Therefore, LDX-exposition in male rats during the peripubertal period causes renal changes in pubertal age involving inflammatory mechanisms, antioxidant activity and apoptosis process.
Assuntos
Antioxidantes , Apoptose , Rim , Dimesilato de Lisdexanfetamina , Estresse Oxidativo , Ratos Wistar , Animais , Masculino , Apoptose/efeitos dos fármacos , Ratos , Rim/efeitos dos fármacos , Rim/metabolismo , Rim/patologia , Antioxidantes/farmacologia , Antioxidantes/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Inflamação/metabolismo , Inflamação/patologia , Maturidade Sexual/efeitos dos fármacosRESUMO
The prevalence of autoimmune diseases has increased worldwide, including in men of reproductive age. Cyclosporine A (CsA) is an immunosuppressive drug commonly used for long periods in the prophylaxis and treatment of autoimmune dysfunction and transplant rejection. Owing to CsA toxicity, most clinical settings use lower CsA doses. Therefore, we evaluated whether a low dose (10 mg/kg) of CsA affects sperm parameters (daily sperm production, motility, morphology, mitochondrial activity, and acrosomal integrity), plasma testosterone levels, and fertility after short-term (10 days) and long-term (50 days) treatments in mice. Short-term CsA treatment partially affected sperm parameters and fertility, as shown by the reduction in sperm hyperactivation and gestational rate 10 days after the interruption of short-term CsA treatment. Long-term CsA treatment impairs sperm count, hyperactivated motility, and acrosomal integrity. This treatment regimen further decreased plasma testosterone concentrations but did not affect reproductive outcomes in mating trials. These outcomes were reversed 50 days after the interruption of long-term CsA treatment. We conclude that a low CsA dose differentially impairs sperm parameters and testicular steroidogenesis in a time-dependent and mostly reversible manner but does not affect male fertility.
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Ciclosporina , Testosterona , Masculino , Camundongos , Animais , Sêmen , Espermatozoides , Testículo , Motilidade dos Espermatozoides , Contagem de EspermatozoidesRESUMO
CONTEXT: Sulfasalazine (SAS) is a drug prescribed for pregnant and breastfeeding women with chronic inflammatory bowel diseases. SAS treatment induces transitory infertility in both adult men and male rats. Although SAS crosses the placenta and passes into maternal milk, the consequences of maternal SAS exposure on the reproductive development of male offspring needs further study. AIMS: The current study evaluated whether maternal SAS exposure interferes with the reproductive development of male rat offspring in the neonatal, infant, pubertal and adulthood periods. METHODS: Pregnant Wistar rats (n =10/group) received 300mg/kg/day of SAS dissolved in carboxymethyl cellulose (CMC), by gavage, from gestational day 0 to lactation day 21, and 3mg/kg/day of folic acid during gestation. The control group received CMC. KEY RESULTS: During puberty, maternal SAS exposure increased the total length of seminiferous tubules, and round cells were observed in the lumen of caput and cauda epididymis. Moreover, SAS induced oxidative stress-related alterations in the testes of infant and adolescent rats. CONCLUSIONS: Although maternal SAS treatment caused reproductive alterations in infant and adolescent male rats, in adulthood, there were no impairments in sperm parameters that could compromise fertility. IMPLICATIONS: This study investigated the consequences of maternal exposure to SAS on the reproductive development of male rat offspring from birth to adulthood, employing a human-relevant dose. Thus, this study provides information for better understanding of SAS treatment during critical periods of development.
Assuntos
Efeitos Tardios da Exposição Pré-Natal , Sulfassalazina , Humanos , Gravidez , Masculino , Ratos , Feminino , Animais , Adolescente , Sulfassalazina/farmacologia , Aleitamento Materno , Ratos Wistar , Sêmen , Lactação , Exposição Materna/efeitos adversosRESUMO
Parabens and phthalates are commonly found as contaminants in human fluids and are able to provoke reproductive toxicity, being considered endocrine disruptors. To evaluate the effects of phthalate and paraben, alone or in combination, on reproductive development of the offspring, female pregnant Wistar rats were allocated in six experimental groups: Three control groups (gavage [CG], subcutaneous [CS], and gavage + subcutaneous) received corn oil as vehicle, and the remaining groups were exposed to di(2-ethylhexyl)phthalate (DEHP) (500 mg/kg, gavage), butyl paraben (BP) (100 mg/kg, subcutaneously), or MIX (DEHP + BP), from Gestational Day 12 until Postnatal Day (PND) 21. The following parameters were assessed on the offspring: anogenital distance and weight at PND 1, nipple counting at PND 13, puberty onset, estrous cycle, weights of reproductive and detoxifying organs, histological evaluation of reproductive organs, and sperm evaluations (counts, morphology, and motility). Female pups from MIX group presented reduced body weight at PND 1, lower AGD, and decreased endometrium thickness. Male animals showed decreased body weight at PND 1 and lower number of Sertoli cells on DEHP and MIX groups, MIX group revealed increase of abnormal seminiferous tubules, DEHP animals presented delayed preputial separation and higher percentage of immotile sperms, and BP males presented diminished number of Leydig cells. In conclusion, the male offspring was more susceptible to DEHP toxicity; even when mixed to paraben, the main negative effects observed seem to be due to antiandrogenic phthalate action. On the other hand, DEHP seems to be necessary to improve the effects of BP on reducing estrogen-dependent and increasing androgen-dependent events.
Assuntos
Dietilexilftalato , Efeitos Tardios da Exposição Pré-Natal , Gravidez , Humanos , Ratos , Animais , Masculino , Feminino , Exposição Materna/efeitos adversos , Dietilexilftalato/toxicidade , Parabenos/toxicidade , Ratos Sprague-Dawley , Ratos Wistar , Maturidade Sexual , Sêmen , Peso Corporal , Efeitos Tardios da Exposição Pré-Natal/induzido quimicamente , Efeitos Tardios da Exposição Pré-Natal/patologia , TestículoRESUMO
Since studies on the reproductive consequences after the exposure to environmentally relevant doses of Benzo(a)pyrene (BaP) during critical stages of development are scarce, this study evaluated female reproductive parameters of adult rats exposed to a low dose of BaP during the juvenile phase. Female rats (Post-natal 21) were treated with BaP (0 or 0.1 µg/kg/day; gavage) for 21 consecutive days. During the treatment, no clinical signs of toxicity were observed. Nevertheless, the ages of vaginal opening and first estrus were anticipated by the BaP-exposure. At the sexual maturity, the juvenile exposure compromised the sexual behavior, as well as the placental efficiency, follicle stimulating hormone levels, placenta histological analysis, and ovarian follicle count. A decrease in erythrocyte, platelet, and lymphocyte counts also was observed in the exposed-females. Moreover, the dose of BaP used in this study was not able to produce estrogenic activity in vivo. These data showed that juvenile BaP-exposure, at environmentally relevant dose, compromised the female reproductive system, possibly by an endocrine deregulation; however, this requires further investigation.
Assuntos
Benzo(a)pireno , Placenta , Ratos , Gravidez , Feminino , Animais , Benzo(a)pireno/toxicidade , Reprodução , Folículo OvarianoRESUMO
Metformin (Met) is widely used to control blood glucose levels and acts on various organs, including reproductive tissues, to improve reproductive and lifespan. This study evaluated whether neonatal Met exposure prevented male reproductive dysfunction caused by being overweight during adulthood. Randomized Wistar rat pups received an intraperitoneal injection from postnatal days (PNDs) 1 to 12of saline (Sal; 0.9% NaCl/day in 2mL/kg) or Met (100 mg/kg/day in 2 mL/kg). From PNDs 60 to 90, the animals received a regular (R; 4.5% fat; Sal R and Met R groups) or a high-fat (HF; 35% fat; Sal HF and Met HF groups) diet. At PND 90, all animals were euthanized to evaluate their biometric and reproductive parameters. The Sal and Met groups with R showed similar body weights, however, the HF diet increased the body weight in both groups. The Sal HF group showed testicular damage regarding in antioxidant status and inflammatory profile in the epididymal cauda. The HF diet reduced Leydig and Sertoli cells numbers, with lower sperm quality. The Met R animals showed positive reproductive programming, due to improved antioxidant defense, inflammatory biomarkers, and sperm morphology. Met HF prevented HF diet damage to reproductive organs and sperm morphology, but not to sperm motility. Early Met exposure positively affected the male reproductive system of adult rats, preventing reproductive HF disorders. STATEMENT OF NOVELTY AND SIGNIFICANCE: Metformin is used to control type 2 diabetes mellitus and can act to improve metabolism and lifespan. Metformin avoidance is recommended during pregnancy, but there is no information regarding its use when breastfeeding. For the first time, we showed in this current study that metformin positively acts in the male reproductive tissues and helps involved in later life. These data showed a better antioxidant defense and anti-inflammatory profile of Metformin animals than Saline animals and might directly improve reproductive organs morphophysiology and sperm morphology. Also, the neonatal Met application programs the male reproduction to counterbalance damages from an obesogenic environment in later life.
Assuntos
Anti-Inflamatórios/administração & dosagem , Antioxidantes/administração & dosagem , Dieta Hiperlipídica/efeitos adversos , Metformina/administração & dosagem , Reprodução/efeitos dos fármacos , Testículo/efeitos dos fármacos , Animais , Animais Recém-Nascidos , Esquema de Medicação , Mediadores da Inflamação/metabolismo , Lactação , Masculino , Estresse Oxidativo/efeitos dos fármacos , Ratos Wistar , Testículo/metabolismo , Testículo/patologia , Testículo/fisiopatologia , Testosterona/sangueRESUMO
Coronavirus disease 2019 (COVID-19), caused by the Severe Acute Respiratory Syndrome Coronavirus type 2 (SARS-CoV-2), is the largest pandemic in modern history with very high infection rates and considerable mortality. The disease, which emerged in China's Wuhan province, had its first reported case on December 29, 2019, and spread rapidly worldwide. On March 11, 2020, the World Health Organization (WHO) declared the COVID-19 outbreak a pandemic and global health emergency. Since the outbreak, efforts to develop COVID-19 vaccines, engineer new drugs, and evaluate existing ones for drug repurposing have been intensively undertaken to find ways to control this pandemic. COVID-19 therapeutic strategies aim to impair molecular pathways involved in the virus entrance and replication or interfere in the patients' overreaction and immunopathology. Moreover, nanotechnology could be an approach to boost the activity of new drugs. Several COVID-19 vaccine candidates have received emergency-use or full authorization in one or more countries, and others are being developed and tested. This review assesses the different strategies currently proposed to control COVID-19 and the issues or limitations imposed on some approaches by the human and viral genetic variability.
RESUMO
Obesity and absence of physical exercise are global problems that affect concentration and sperm quality in the male reproductive system. The purpose of this study was to examine the effect of obesity and resistance training, considered separately or in association, on testicular function and reproductive capacity. Twenty pubertal male Wistar rats were distributed into four groups: control (C) and exercise (E) groups that received standard rat chow; and obese (O) and obese with exercise (OE) groups that received a high-fat diet. All the groups received filtered water during the experimental conditions. Groups E and OE were submitted to 8 weeks of high-intensity intermittent training. Afterwards, testes were collected for sperm count, spermatogenic kinetics, histopathology, morphometry and immunodetection of androgen receptors (AR). The vas deferens was collected for sperm morphology. The results showed that obesity increased body weight, naso-anal length, liver and epididymal fat weight, abnormal spermatozoa and immunodetectable AR. Intermittent exercise decreased daily sperm production (DSP), sperm count and normal spermatozoa, whereas the number of tubules with immunodetectable AR increased. The combination of obesity and intermittent training led to reduced sperm count and DSP, although abnormal spermatozoa and the number of tubules with immunodetectable AR increased. Thus, in conclusion, both obesity and resistance training impaired testicular function during puberty in rats; and this type of exercise has also been shown to be detrimental to testicular physiology.
Assuntos
Obesidade/complicações , Treinamento Resistido/efeitos adversos , Espermatogênese , Espermatozoides/patologia , Testículo/patologia , Animais , Modelos Animais de Doenças , Cinética , Masculino , Obesidade/metabolismo , Obesidade/patologia , Ratos Wistar , Receptores Androgênicos , Contagem de Espermatozoides , Testículo/metabolismoRESUMO
Malathion is an organophosphate pesticide used in agriculture and control of the Aedes aegypti mosquito. As previous reports have indicated the potential of malathion to compromise testosterone production in in vivo models, the objective of this study was to elucidate the mechanisms underlying the impairment of Leydig cell function, considering its critical role in male reproductive function. To this end, murine Leydig TM3 cells were exposed to concentrations of 1, 10, 100 or 1000⯵M malathion for 24â¯h for evaluation of the compound on cell viability. Subsequently, concentrations of 1, 10, and 100⯵M malathion were employed for a 24-h period to assess testosterone biosynthesis, levels of cytokines IL-1ß, IL-6, IL-10, and TNF-α, as well as the redox profile. Malathion exerted a concentration-dependent impact on cell viability. Notably, the lower concentrations of malathion (1 and 10⯵M) were found to impair testosterone biosynthesis in TM3 cells. While there were changes in IL-1 and TNF-α levels at specific concentrations, no direct correlation with altered hormone production was established. Our investigation revealed that varied malathion concentrations induced oxidative stress by increase in superoxide anion and a compensatory rise in antioxidants. In conclusion, the observed changes in the oxidative profile of TM3 cells were linked to functional impairment, evidenced by reduced testosterone biosynthesis at lower malathion concentrations.
Assuntos
Sobrevivência Celular , Inseticidas , Células Intersticiais do Testículo , Malation , Oxirredução , Estresse Oxidativo , Testosterona , Malation/toxicidade , Animais , Testosterona/biossíntese , Masculino , Células Intersticiais do Testículo/efeitos dos fármacos , Células Intersticiais do Testículo/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Camundongos , Inseticidas/toxicidade , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Citocinas/metabolismoRESUMO
Malathion serves as a pivotal pesticide in agriculture and the management of the Aedes aegypti mosquito. Despite its widespread use, there is a notable absence of studies elucidating the mechanisms through which malathion may affect the female reproductive system. Consequently, the objective of this investigation was to assess whether exposing juvenile female rats to low doses of malathion during the juvenile and peripubertal periods could compromise pubertal onset, estradiol levels, and the integrity of the ovaries and uterus while also examining the underlying mechanisms of damage. To achieve this, thirty juvenile female rats were subjected to either a vehicle or malathion (10 mg/kg or 50 mg/kg) between postnatal days 22 and 60, with subsequent verification of pubertal onset. Upon completion of the exposure period, blood samples were collected for estradiol assessment. The ovaries and uterus were then examined to evaluate histological integrity, oxidative stress, and the expression of genes associated with cell proliferation, antiapoptotic responses, and endocrine pathways. Although estradiol levels and pubertal onset remained unaffected, exposure to malathion compromised the integrity and morphometry of the ovaries and uterus. This was evidenced by altered oxidative profiles and changes in the expression of genes regulating the cell cycle, anti-apoptotic processes, and endocrine pathways. Our findings underscore the role of malathion in inducing cell proliferation, promoting cell survival, and causing oxidative damage to the female reproductive system in rats exposed during peripubertal periods.
Assuntos
Inseticidas , Malation , Ratos , Feminino , Animais , Malation/toxicidade , Inseticidas/toxicidade , Ovário , Estresse Oxidativo , Estradiol , Útero , Expressão GênicaRESUMO
Chlorpyrifos is an organophosphate insecticide used to control pests in crops. Thus, humans are constantly exposed through ingestion of contaminated food or water, inhalation of contaminated air, and through the skin. The juvenile and peripubertal periods comprise a window of development of the reproductive system, sensitive to toxic agents. Considering the scarcity of data on exposure to the insecticide during these periods, the aim of this study was to evaluate the effects of chlorpyrifos on the testis during the juvenile and peripubertal periods. Thirty Wistar rats with an initial age of 25 days were distributed into 3 groups: control, which received corn oil (vehicle); CPS5, which received 5â¯mg/Kg b.w. of chlorpyrifos; and CPS15, which received 15â¯mg/Kg b.w. of chlorpyrifos. The groups were treated via gavage daily for 40 days and on the 41st experimental day, the animals were anesthetized and submitted to euthanasia to collect the organs. Blood was collected to obtain plasma and testosterone measurement. The testicles were removed, weighed and used for sperm count analyses, histopathological and morphometric analyzes and for oxidative stress analyses. Spermatozoa from the vas deferens were collected for analyzes of sperm morphology and acrosome integrity. The results showed that the two concentrations of chlorpyrifos caused a decrease in the number of Leydig and Sertoli cells and germ cells and increased the number of morphologically abnormal sperm and sperm with acrosomal damage. Furthermore, a decrease in lipid peroxidation was observed in the CPS5 and CPS15 groups, and a decrease in glutathione-S-transferase activity in the CPS5 group. We conclude that exposure to chlorpyrifos harms the daily production of sperm, as well as their quality, in addition to causing an imbalance in the oxidoreductive balance of the testicle.
Assuntos
Clorpirifos , Inseticidas , Células Intersticiais do Testículo , Ratos Wistar , Células de Sertoli , Espermatozoides , Animais , Masculino , Clorpirifos/toxicidade , Inseticidas/toxicidade , Espermatozoides/efeitos dos fármacos , Espermatozoides/patologia , Células Intersticiais do Testículo/efeitos dos fármacos , Células Intersticiais do Testículo/patologia , Células Intersticiais do Testículo/metabolismo , Células de Sertoli/efeitos dos fármacos , Células de Sertoli/metabolismo , Células de Sertoli/patologia , Ratos , Maturidade Sexual/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Testosterona/sangue , Testículo/efeitos dos fármacos , Testículo/patologia , Testículo/metabolismo , Contagem de EspermatozoidesRESUMO
Topiramate (TPM) is an antiepileptic drug used for treating epilepsy in children, and migraine in teenagers. In this context, preclinical studies with adult female rats observed reproductive system abnormalities following treatment with TPM. Additionally, exposure to endocrine disruptors during developmental plasticity periods, such as childhood and adolescence, may influence characteristics in the adult individual. This study evaluated whether treatment with TPM during developmental periods influences the reproductive system of female rats either immediately or in adult life. Female Wistar rats were treated with TPM (41â¯mg/Kg/day) by oral gavage from postnatal day (PND) 16-28, or PND 28-50, which correspond to childhood and adolescence, respectively, and euthanized either 24â¯h after the final administration or during adulthood. Treatment with TPM during adolescence induced short-term increase in uterus and ovary weights and reduction in endometrial stroma thickness. Adult animals treated during adolescence displayed reduced primordial ovarian follicles' numbers, and increased primary and pre-antral ovarian follicles' numbers. Treatment during childhood induced no short or long-term differences. These results indicate TPM treatment during adolescence is capable of inducing short and long-term alterations on the reproductive system of female Wistar rats.
Assuntos
Anticonvulsivantes , Ovário , Ratos Wistar , Topiramato , Útero , Animais , Feminino , Topiramato/toxicidade , Anticonvulsivantes/toxicidade , Ovário/efeitos dos fármacos , Útero/efeitos dos fármacos , Frutose/toxicidade , Frutose/análogos & derivados , Tamanho do Órgão/efeitos dos fármacos , RatosRESUMO
Malathion is an insecticide that is used to control arboviruses and agricultural pests. Adolescents that are exposed to this insecticide are the most vulnerable as they are in the critical period of postnatal sexual development. This study aimed to evaluate whether malathion damage can affect sperm function and its respective mechanisms when adolescents are exposed during postnatal sexual development. Twenty-four male Wistar rats (PND 25) were divided into three experimental groups and treated daily for 40 d: control group (saline 0.9%), 10 mg/kg (M10 group), or 50 mg/kg (M50 group) of malathion. At PND 65, the rats were anesthetized and euthanized. Testicles were collected for the evaluation of gene expression. Sperm cells from the epididymis were used for evaluation of the oxidative profile or spermatic function. Data showed that a lower dose of malathion downregulated the gene expression of androgen receptors and testosterone converter enzyme 17-ß-HSD in the testis. The acrosomal integrity of sperm cells was compromised in the M50 group, but not the M10 group. The mitochondrial activity was not impaired by exposure. Finally, although no alterations in malondialdehyde and glutathione levels were observed, malathion, at both doses, increased antioxidant enzyme catalase activity and, at a higher dose, superoxide dismutase activity. The present study showed that low doses of malathion considered to be inoffensive are capable of impairing sperm quality and function through the downregulation of testicular genic expression of AR enzyme 17-ß-HSD and can damage the spermatic antioxidant profile during critical periods of development.
Assuntos
Inseticidas , Testículo , Animais , Masculino , Ratos , Antioxidantes , Expressão Gênica , Inseticidas/toxicidade , Inseticidas/metabolismo , Malation/toxicidade , Malation/metabolismo , Ratos Wistar , Receptores Androgênicos/genética , Receptores Androgênicos/metabolismo , Sêmen/metabolismo , Espermatozoides , Testículo/metabolismo , 17-Hidroxiesteroide DesidrogenasesRESUMO
INTRODUCTION: It has been suggested that maternal exposure to constant light during the gestational period could be considered as a chronic stressor, impairing offspring development by interfering in neuroendocrine and behavior responses. OBJECTIVE: This study aimed to evaluate whether maternal exposure to continuous light during pregnancy affects the adult reproductive system in the female offspring. MATERIALS AND METHODS: Pregnant Wistar rats were allocated into light-dark (LD) group, exposed to light and dark photoperiod during gestation, and the light-light (LL) group, exposed to a photoperiod of constant light during gestation. After birth, pups were maintained under normal light-dark photoperiod until adulthood. At postnatal day 90, blood was collected from the female offspring, to analyze plasma luteinizing hormone (LH) and progesterone levels, and the uterus and ovaries were harvested for morphometric, histological, and oxidative stress evaluations. RESULTS AND DISCUSSION: Female exposure to continuous light during the intrauterine period resulted in the adult reduction of LH and increased progesterone plasma levels, and uterine injuries a higher number of endometrial glands and reduced levels of antioxidant enzymes, such as glutathione reductase and glutathione S-transferase. In these experimental conditions, gestational continuous light exposure disturbs sex hormone balance and reduces the antioxidant enzymatic activity in the uterus of female offspring in adult life.
Assuntos
Antioxidantes , Progesterona , Ratos , Gravidez , Animais , Feminino , Ratos Wistar , Hormônio Luteinizante , ÚteroRESUMO
Protein restriction during early phases of body development, such as intrauterine life can favor the development of vascular disorders. However, it is not known if peripubertal protein restriction can favor vascular dysfunction in adulthood. The present study aimed to evaluated whether a protein restriction diet during peripubertal period favors endothelial dysfunction in adulthood. Male Wistar rats from postnatal day (PND) 30 until 60 received a diet with either 23% protein (CTR group) or with 4% protein (LP group). At PND 120, the thoracic aorta reactivity to phenylephrine, acetylcholine, and sodium nitroprusside was evaluated in the presence or absence of: endothelium, indomethacin, apocynin and tempol. The maximum response (Rmax) and pD2 (-log of the concentration of the drug that causes 50% of the Rmax) were calculated. The lipid peroxidation and catalase activity were also evaluated in the aorta. The data were analyzed by ANOVA (one or two-ways and Tukey's) or independent t-test; the results were expressed as mean ± S.E.M., p < 0.05. The Rmax to phenylephrine in aortic rings with endothelium were increased in LP rats when compared with the Rmax in CTR rats. Apocynin and tempol reduced Rmax to phenylephrine in LP aortic rings but not in CTR. The aortic response to the vasodilators was similar between the groups. Aortic catalase activity was lower and lipid peroxidation was greater in LP compared to CTR rats. Therefore, protein restriction during the peripubertal period causes endothelial dysfunction in adulthood through a mechanism related to oxidative stress.
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The hyperhomocysteinemia (HHcy) is toxic to the cells and associated with several diseases. Clinical studies have shown changes in plasma concentrations of Hcy after physical exercise. This study aimed to assess the effect of HHcy on testis, epididymis and sperm quality and to investigate whether voluntary exercise training protects this system against damage caused by HHcy in Swiss mice. In this study, 48 mice were randomly distributed in the control, HHcy, physical exercise, and HHcy combined with physical exercise groups. HHcy was induced by daily administration of dl-homocysteine thiolactone via gavage throughout the experimental period. Physical exercise was performed through voluntary running on the exercise wheels. The plasma concentrations of homocysteine (Hcy) and testosterone were determined. The testes and epididymis were used to assess the sperm count, histopathology, lipoperoxidation, cytokine levels, testicular cholesterol, myeloperoxidase, and catalase activity. Spermatozoa were analyzed for morphology, acrosome integrity, mitochondrial activity, and motility. In the testes, HHcy increased the number of abnormal seminiferous tubules, reduced the tubular diameter and the height of the germinal epithelium. In the epididymis, there was tissue remodeling in the head region. Ultimately, voluntary physical exercise training reduced plasma Hcy concentration but did not attenuate HHcy-induced testicular and epididymal disturbances.
Assuntos
Epididimo/fisiopatologia , Hiper-Homocisteinemia/terapia , Condicionamento Físico Animal/fisiologia , Testículo/fisiopatologia , Animais , Catalase/sangue , Epididimo/metabolismo , Homocisteína/sangue , Hiper-Homocisteinemia/sangue , Hiper-Homocisteinemia/fisiopatologia , Masculino , Camundongos , Estresse Oxidativo/fisiologia , Testículo/metabolismo , Testosterona/sangue , Substâncias Reativas com Ácido Tiobarbitúrico/metabolismoRESUMO
Leydig cells play pivotal roles in eliciting male characteristics by producing testosterone and any damage to these cells can compromise male fertility Toxoplasma gondii (T. gondii) is an intracellular parasite capable to invade any nucleated cell, including cells from male reproductive system. Herein, we evaluated the capacity of RH strain of T. gondii to infect TM3 Leydig cells and the impact of this infection on testosterone and inflammatory mediators production. We first, by performing adherence, infection, and intracellular proliferation assays, we found a significant increase in the number of infected Leydig cells, peaking 48 h after the infection with T. gondii. Supernatants of TM3 infected cells exhibited, in a time-dependent manner, increased levels of testosterone as well as monocyte chemoattractant protein-1 (MCP-1) and interferon-γ (IFN-γ), which is correlated with the robust T. gondii infection. In conclusion, our study provides new insights regarding the harmful effects of T. gondii infection on male reproductive system.
Assuntos
Células Intersticiais do Testículo/parasitologia , Testosterona/biossíntese , Toxoplasmose/metabolismo , Animais , Quimiocina CCL2/biossíntese , Interferon gama/biossíntese , Masculino , Camundongos Endogâmicos BALB C , Fatores de Tempo , ToxoplasmaRESUMO
Alterations in the circadian cycle are known to cause physiological disorders in the hypothalamic-pituitary-adrenal and the hypothalamic-pituitary-gonadal axes in adult individuals. Therefore, the present study aimed to evaluate whether exposure of pregnant rats to constant light can alter the reproductive system development of male offspring. The dams were divided into two groups: a light-dark group (LD), in which pregnant rats were exposed to an LD photoperiod (12 h/12 h) and a light-light (LL) group, in which pregnant rats were exposed to a photoperiod of constant light during the gestation period. After birth, offspring from both groups remained in the normal LD photoperiod (12 h/12 h) until adulthood. One male of each litter was selected and, at adulthood (postnatal day (PND) 90), the trunk blood was collected to measure plasma testosterone levels, testes and epididymis for sperm count, oxidative stress and histopathological analyses, and the spermatozoa from the vas deferens to perform the morphological and motility analyses. Results showed that a photoperiod of constant light caused a decrease in testosterone levels, epididymal weight and sperm count in the epididymis, seminiferous tubule diameter, Sertoli cell number, and normal spermatozoa number. Histopathological damage was also observed in the testes, and stereological alterations, in the LL group. In conclusion, exposure to constant light during the gestational period impairs the reproductive system of male offspring in adulthood.
Assuntos
Ritmo Circadiano , Genitália Masculina/crescimento & desenvolvimento , Luz/efeitos adversos , Efeitos Tardios da Exposição Pré-Natal/patologia , Animais , Feminino , Genitália Masculina/patologia , Masculino , Estresse Oxidativo , Gravidez , Efeitos Tardios da Exposição Pré-Natal/etiologia , Ratos Wistar , Espermatogênese , Testosterona/sangueRESUMO
It is well established that sibutramine produces weight loss and is used frequently in women of childbearing age. However, the potential adverse consequences attributed to sibutramine use by women who may become pregnant is not known. It was thus of interest to determine the effects of sibutramine on the reproductive performance of pregnant rats. Overweight as well as non-overweight female Wistar rats were treated with sibutramine (6 mg/kg) orally, daily for 15 d and then mated with normal male rats. Pregnancy was confirmed and treatment continued with sibutramine until d 14 of pregnancy. On d 20 of pregnancy all rats were anesthetized for determination of various maternal and fetal parameters. There was a significant maternal weight reduction at the end of pregnancy in the non-overweight drug-treated group compared to the control (non-overweight, no drug). Sibutramine alone and overweight condition alone produced a significant increase in postimplantation loss and placental index. In the overweight with or without sibutramine groups a significant decrease in fetal weight was noted. Data suggest that sibutramine alone or the condition of excess weight in the absence of drugs produced impaired reproductive performance. However, treatment of overweight rats with sibutramine did not further exacerbate fetal loss compared to sibutramine alone or the effects noted with excess weight alone.
Assuntos
Depressores do Apetite/farmacologia , Ciclobutanos/farmacologia , Perda do Embrião/induzido quimicamente , Sobrepeso/complicações , Redução de Peso/efeitos dos fármacos , Animais , Feminino , Gravidez , Ratos , Ratos WistarRESUMO
The original publication of this paper contains a mistake.