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1.
Hinyokika Kiyo ; 65(6): 215-218, 2019 Jun.
Artigo em Japonês | MEDLINE | ID: mdl-31501388

RESUMO

A 56-year-old man presented with a painless swelling of the left scrotum. Cytologic examination of blood stained hydrocele fluid suggested malignancy. Left high orchiectomy was performed under the suspicion of malignant tumor of the tunica vaginalis testis. The final pathologic report revealed malignant mesothelioma of the tunica vaginalis testis. There is no evidence of recurrence after 114 months followup. It is important to perform en bloc resection for this disease to prevent recurrence.


Assuntos
Mesotelioma , Neoplasias Testiculares , Humanos , Masculino , Mesotelioma/cirurgia , Pessoa de Meia-Idade , Orquiectomia , Neoplasias Testiculares/diagnóstico , Neoplasias Testiculares/cirurgia , Testículo/patologia
2.
Chem Biol Interact ; 312: 108792, 2019 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-31491373

RESUMO

Cadmium (Cd) is an important toxic chemical due to its increasing levels in the environment and bioaccumulation in humans and animals. The present study was performed to evaluate the effects of long-term exposure to 1, 10, or 100 µg/L Cd in drinking water on the development, reproduction and neurotoxicity of offspring when administered to mice from parental puberty to postnatal 10 weeks in offspring. The development parameters measured in offspring included physical development, reflex ontogeny, body weight and body size. The reproductive indices measured consisted of anogenital distances (AGDs), estrous cycle, sperm quality, specific gene expression in Leydig or Sertoli cells, seminiferous epithelium cycle, sex hormone levels, histological morphology and apoptosis in testis or ovary, and the levels of oxidative stress. The determination of neurotoxicity included learning and memory ability, anxiety, and related serum indicators. In addition, blood lipid level, liver and kidney function were also determined by serum biochemical assays. The results showed that exposure to Cd in the present model had no adverse effects on development, but had some reproductive toxicity and neurotoxicity, including alteration of spermatogenic epithelial staging in testis and inducing anxiety in offspring. Furthermore, the levels of total protein, globulins, total bile acid and direct bilirubin were also significantly altered, especially in female offspring. The present study suggested that long-term exposure to low doses of Cd had adverse effects on the health of the next generation, and some harmful effects showed gender differences in offspring. The present study demonstrated that attention should be paid to Cd pollution in the environment, especially before pregnancy.


Assuntos
Cádmio/toxicidade , Reprodução/efeitos dos fármacos , Animais , Análise Química do Sangue , Feminino , Células Intersticiais do Testículo/efeitos dos fármacos , Células Intersticiais do Testículo/metabolismo , Masculino , Aprendizagem em Labirinto/efeitos dos fármacos , Camundongos , Ovário/efeitos dos fármacos , Ovário/metabolismo , Ovário/patologia , Gravidez , Efeitos Tardios da Exposição Pré-Natal , Células de Sertoli/efeitos dos fármacos , Células de Sertoli/metabolismo , Espermatozoides/efeitos dos fármacos , Espermatozoides/fisiologia , Esteroide 17-alfa-Hidroxilase/genética , Esteroide 17-alfa-Hidroxilase/metabolismo , Testículo/efeitos dos fármacos , Testículo/metabolismo , Testículo/patologia
3.
Toxicol Lett ; 316: 60-72, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31520699

RESUMO

Cholestasis is a significant decrease in bile flow. The liver is the primary organ affected by cholestasis. Chronic cholestasis could entail to tissue fibrotic changes and liver cirrhosis. Other organs, including heart, kidneys, nervous system, skeletal muscles, as well as the reproductive system, might also be affected during cholestasis. Although the cholestasis-associated pathological and biochemical alterations in organs such as liver have been widely investigated, there is little information about complications such as cholestasis-induced reproductive toxicity. The current study aimed to evaluate the pathologic effects of cholestasis on reproductive organs in both male and female animals. Rats underwent bile duct ligation (BDL) surgery. Markers of reproductive toxicity, including serum hormonal changes, tissue histopathological alterations, biomarkers of oxidative stress, and markers of mitochondrial impairment, were evaluated. Increased serum markers of liver injury and elevated level of cytotoxic molecules such as bile acids and bilirubin were evident in BDL animals. On the other hand, the serum level of hormones such as testosterone was suppressed in BDL rats. Significant histopathological alterations were also evident in the testis and ovary of BDL animals. A significant increase in oxidative stress markers, including ROS formation, lipid peroxidation, protein carbonylation, and depleted glutathione and antioxidant reservoirs were also detected in BDL rats. Moreover, mitochondrial depolarization decreased dehydrogenases activity, and depleted ATP content was detected in sperm isolated from the BDL group. These data indicate that cholestasis-associated reproductive toxicity in male and female rats is restrictedly coupled with severe oxidative stress and mitochondrial impairment.


Assuntos
Colestase/metabolismo , Mitocôndrias/metabolismo , Ovário/metabolismo , Estresse Oxidativo , Reprodução , Espermatozoides/metabolismo , Testículo/metabolismo , Animais , Colestase/etiologia , Colestase/fisiopatologia , Ducto Colédoco/cirurgia , Modelos Animais de Doenças , Feminino , Ligadura , Peroxidação de Lipídeos , Masculino , Mitocôndrias/patologia , Ovário/patologia , Ovário/fisiopatologia , Carbonilação Proteica , Ratos Sprague-Dawley , Medição de Risco , Testículo/patologia , Testículo/fisiopatologia
4.
Urologe A ; 58(10): 1198-1200, 2019 Oct.
Artigo em Alemão | MEDLINE | ID: mdl-31468078

RESUMO

Bilateral intrauterine testicular torsion is an extremely rare emergency and can be difficult to diagnose due to its diverse manifestation and potential differential diagnoses. In time surgical intervention is crucial for the retention of testicular function. We present a newborn with a bilateral testicular torsion, in which one testicle could be saved after detorsion. The contralateral side showed hemorrhagic infarction and was removed. Since organ preservation is rarely successful, the surgical therapy is discussed controversially.


Assuntos
Orquiectomia/métodos , Torção do Cordão Espermático/congênito , Testículo/anormalidades , Diagnóstico Diferencial , Emergências , Humanos , Recém-Nascido , Masculino , Escroto , Torção do Cordão Espermático/cirurgia , Testículo/patologia , Testículo/cirurgia , Resultado do Tratamento
5.
Life Sci ; 232: 116655, 2019 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-31306659

RESUMO

AIMS: The deleterious effect of gamma radiation on testicular tissue is a challenging problem in nuclear medicine. This study investigated the potential radioprotective effect of mitoquinol (MitoQ), a mitochondria-targeted antioxidant, against testicular damage induced by gamma irradiation in rats. MAIN METHODS: Rats were allocated into four groups. The first group served as the control, the second group received MitoQ (2 mg / kg / day; i.p.) for seven days, the third group was exposed to gamma radiation (5 Gy as a single dose) and the last group received MitoQ prior to irradiation. Rats were sacrificed. Then, sperm analyses and the serum testosterone were determined. Moreover, evaluation of mitochondrial oxidative stress parameters (SOD, GSH and GPx) as well as apoptosis indicators (cytochrome-c, Bax, Bcl-2 and caspase-3) was performed. Additionally, analysis of steroidogensis biomarkers (StAR, 3ß-HSD and 17ß-HSD) and histopathological investigations were carried out. KEY FINDINGS: MitoQ replenished mitochondrial SOD, GPx and GSH indicating its strong antioxidant effect in addition to its energy preservation manifested by the elevated ATP. MitoQ inhibited the intrinsic apoptosis via diminution of Bax, cytochrome-c and caspase-3 and alleviation of Bcl-2. This antioxidant conferred protection to steroidogenesis as verified by the increase in testosterone and the up-regulation of StAR, 3ß-HSD and 17ß-HSD expression; these effects might be correlated with its antioxidant/anti-apoptotic potential. Histopathological and sperm analyses corroborated the biochemical findings. SIGNIFICANCE: This study identifies MitoQ as a novel agent for the management of testicular toxicity induced by gamma irradiation.


Assuntos
Raios gama , Mitocôndrias/efeitos dos fármacos , Compostos Organofosforados/farmacologia , Esteroides/biossíntese , Testículo/efeitos dos fármacos , Testículo/efeitos da radiação , Ubiquinona/farmacologia , Trifosfato de Adenosina/metabolismo , Animais , Apoptose/efeitos dos fármacos , Peso Corporal/efeitos dos fármacos , Masculino , Mitocôndrias/metabolismo , Tamanho do Órgão/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Ratos , Ratos Wistar , Espermatogênese/efeitos dos fármacos , Espermatogênese/efeitos da radiação , Testículo/patologia , Irradiação Corporal Total
6.
New Microbiol ; 42(3): 184-187, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31305938

RESUMO

Tuberculosis (TB) of the testicle is a rarely reported and poorly described disease localization. There are no well-defined clinical features suggestive of testicular TB, which makes the diagnosis difficult to establish, especially in low-income settings like Mozambique, where TB is endemic and often associated with HIV-infection; both considered leading causes of death worldwide. We reported the case of a 45-year-old male, HIV positive, naïve to antiretroviral treatment, admitted to the Department of Medicine of the Central Hospital of Beira to investigate chronic enlargement of the testicles.


Assuntos
Infecções por HIV , Doenças Testiculares , Tuberculose , Antirretrovirais , Infecções por HIV/complicações , Humanos , Masculino , Pessoa de Meia-Idade , Moçambique , Doenças Testiculares/diagnóstico , Doenças Testiculares/microbiologia , Doenças Testiculares/patologia , Testículo/microbiologia , Testículo/patologia , Tuberculose/complicações , Tuberculose/diagnóstico , Tuberculose/patologia
7.
Aquat Toxicol ; 213: 105204, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31185427

RESUMO

Previous toxicological investigations of the insensitive munition (IM), 3-nitro-1,2,4-triazol-5-one (NTO), demonstrated histopathological and physiological impacts in mammalian testes. The implications of these findings for fish was unknown, therefore we investigated the effects of chronic (21 day) exposures to NTO and an NTO-containing IM formulation called IMX-101 (composed of 2,4-dinitroanisole (DNAN), nitroguanidine (NQ), and NTO) in adult male fathead minnows to assess if impacts on testes were conserved. The NTO exposure caused no significant mortality through the maximum exposure concentration (720 mg/L, measured), however NTO elicited testicular impacts causing significant asynchrony in spermatogenesis and necrosis in secondary spermatocytes at the two highest exposure concentrations (383 mg/L and 720 mg/L) and testicular degeneration at the highest exposure. Microarray-based transcriptomics analysis identified significant enrichment of steroid metabolism pathways and mTORC-signal control of spermatogonia differentiation in NTO exposures each having logical connections to observed asynchronous spermatogenesis. Additionally, NTO impaired transcriptional expression for genes supporting sperm structural and flagellar development including sperm-associated antigen 6 (Spag6). These functional transcriptomic responses are hypothesized contributors to impacted reproductive physiology in NTO exposures that ultimately lead to reductions in spermatozoa. In contrast to NTO, the IMX-101 formulation elicited significant mortality at the two highest exposure concentrations of 25.2 and 50.9 mg/L (DNAN nominal + NTO measured + NQ measured). Unlike NTO and NQ, the DNAN component of the IMX-101 formulation underwent significant transformation in the 21d exposure. From previous investigations, neither NTO nor NQ caused mortality in fish at >1000 mg/L suggesting that mortality in the present study arose from DNAN / DNAN-attributable transformation products. The 12.6 mg/L IMX-101 exposure caused significant sublethal impacts on testes including sperm necrosis, interstitial fibrosis, and Sertoli-like cell hyperplasia. Transcriptional profiles for IMX-101 indicated significant enrichment on multiple signaling pathways supporting spermatogenesis, mitosis / meiosis, and flagellar structure, all logically connected to observed sperm necrosis. Additionally, pronounced transcriptional increases within the PPARα-RXRα pathway, a known DNAN target, has been hypothesized to correspond to Sertoli cell hyperplasia, presumably as a compensatory response to fulfill the nurse-function of Sertoli cells during spermatogenesis. Overall, the transcriptional results indicated unique molecular responses for NTO and IMX-101. Regarding chemical hazard, NTO impacted testes and impaired spermatogenesis, but at high exposure concentrations (≥ 192 mg/L), whereas the IMX-101 formulation, elicited mortality and impacts on reproductive physiology likely caused by DNAN and its transformation products present at concentrations well below the NTO-component concentration within the IMX-101 mixture formulation.


Assuntos
Anisóis/toxicidade , Cyprinidae/fisiologia , Nitrocompostos/toxicidade , Testículo/fisiologia , Triazóis/toxicidade , Animais , Cyprinidae/genética , Masculino , Análise de Componente Principal , Reprodução/efeitos dos fármacos , Espermatogênese , Testículo/efeitos dos fármacos , Testículo/patologia , Transcriptoma/genética , Poluentes Químicos da Água/toxicidade
8.
Int Braz J Urol ; 45(4): 815-824, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31184457

RESUMO

INTRODUCTION: Chronic hyperglycemia is caused by diabetes mellitus-committed genital morphophysiology, and oxidative stress is one of the main factors involved in this process. Alpha lipoic acid (ALA) can prevent metabolic and morphological changes in diabetic individuals. OBJECTIVES: In present study, we evaluated the effects of regular ALA consumption on the spermatogenesis and histoarchitecture in the male genital system of diabetic rats. MATERIALS AND METHODS: Thirty-two Wistar rats were divided into groups: Control (CG); Diabetic Control (DCG), receiving commercial diet: ALA Group (ALAG) and Diabetic ALA Group (DALAG), fed diets with added ALA (300 mg/Kg bw). The diabetic groups received a single injection of streptozotocin (60 mg/kg). After sixty days of the diet, the animals were euthanized, and semen, testis and epididymis samples were collected. A histomorphometric analysis was performed to determine the epithelial height, tubular and luminal diameter, tubular and luminal area of seminiferous tubules and each epididymal region. Sertoli cells were evidenced using the antivimentin antibody and were quantified. The results were statistically analyzed by the ANOVA test. RESULTS: At the end of the experiment, the DALAG glycemia was signifi cantly lower than DCG. The histomorphometric parameters of the seminiferous and epididymal tubules did not show improvement in the DALAG. However, there was an improvement in the DALAG in terms of the concentration, motility and percentage of spermatic pathologies, as well as in the number of Sertoli cells (p<0.001). CONCLUSIONS: The results demonstrated that supplementation with the ALA antioxidant retards testicular lesions and preserve the process of spermatogenesis in diabetes.


Assuntos
Antioxidantes/farmacologia , Diabetes Mellitus Experimental/patologia , Epididimo/efeitos dos fármacos , Espermatozoides/efeitos dos fármacos , Testículo/efeitos dos fármacos , Ácido Tióctico/farmacologia , Animais , Diabetes Mellitus Experimental/fisiopatologia , Epididimo/patologia , Imuno-Histoquímica , Masculino , Distribuição Aleatória , Ratos Wistar , Reprodutibilidade dos Testes , Células de Sertoli , Contagem de Espermatozoides , Motilidade Espermática/efeitos dos fármacos , Espermatogênese/efeitos dos fármacos , Espermatogênese/fisiologia , Espermatozoides/fisiologia , Testículo/patologia , Testículo/fisiopatologia
9.
Cancer Immunol Immunother ; 68(7): 1039-1058, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31165204

RESUMO

The emergence of immunotherapy has revolutionized medical oncology with unprecedented advances in cancer treatment over the past two decades. However, a major obstacle in cancer immunotherapy is identifying appropriate tumor-specific antigens to make targeted therapy achievable with fewer normal cells being impaired. The similarity between placentation and tumor development and growth has inspired many investigators to discover antigens for effective immunotherapy of cancers. Placenta-specific 1 (PLAC1) is one of the recently discovered placental antigens with limited normal tissue expression and fundamental roles in placental function and development. There is a growing body of evidence showing that PLAC1 is frequently activated in a wide variety of cancer types and promotes cancer progression. Based on the restricted expression of PLAC1 in testis, placenta and a wide variety of cancers, we have designated this molecule with new terminology, cancer-testis-placenta (CTP) antigen, a feature that PLAC1 shares with many other cancer testis antigens. Recent reports from our lab provide compelling evidence on the preferential expression of PLAC1 in prostate cancer and its potential utility in prostate cancer immunotherapy. PLAC1 may be regarded as a potential CTP antigen for targeted cancer immunotherapy based on the available data on its promoting function in cancer development and also its expression in cancers of different histological origin. In this review, we will summarize current data on PLAC1 with emphasis on its association with cancer development and immunotherapy.


Assuntos
Antígenos de Neoplasias/imunologia , Antineoplásicos Imunológicos/uso terapêutico , Biomarcadores Tumorais/antagonistas & inibidores , Neoplasias/terapia , Proteínas da Gravidez/antagonistas & inibidores , Antígenos de Neoplasias/metabolismo , Antineoplásicos Imunológicos/farmacologia , Biomarcadores Tumorais/imunologia , Biomarcadores Tumorais/metabolismo , Progressão da Doença , Feminino , Humanos , Imunoterapia/métodos , Masculino , Terapia de Alvo Molecular/métodos , Neoplasias/imunologia , Neoplasias/patologia , Placenta/patologia , Gravidez , Proteínas da Gravidez/imunologia , Proteínas da Gravidez/metabolismo , Testículo/patologia
10.
Ecotoxicol Environ Saf ; 181: 548-558, 2019 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-31234069

RESUMO

Fenpropathrin (FNP) is a member of the synthetic pyrethroids. Herein, the present study was conducted to investigate, for the first time, the potentially harmful effects of FNP on the reproductive system of male rats. In addition, the prophylactic or concurrent influence of camel milk (CM) was assessed. Adult male rats were divided into five groups; control, vehicle control (oil), CM (2ml/rat/day), FNP (15mg/kg bwt/60 days), CM/FNP (prophylaxis) and FNP /CM (co-treated) groups. Sperm morphology, count, serum testosterone (TES), luteinizing hormone (LH) and follicle-stimulating hormone (FSH), thiobarbituric acid reactive substances (TBARS), total antioxidant capacity (TAC), superoxide dismutase (SOD), testicular enzymes, and comet assay analysis were estimated. In addition, histopathology, the ultrastructure of testicular tissue and apoptosis were evaluated. Reduced body weight and gonadosomatic index were observed in the FNP exposed group. TES, LH, FSH were markedly declined following FNP treatment. SOD and TAC concentrations were reduced while PC and TBARS were significantly elevated in FNP group indicating oxidative stress. Furthermore, FNP induced DNA damage and apoptosis in the testis which was evidenced histopathologically and by electron microscope examination. CM significantly counteracted FNP reprotoxic effects, particularly at the prophylactic routine (CM/FNP) than the co-exposure (FNP/CM) one. Conclusively, these findings verified that CM could be a potential candidate therapy against FNP reprotoxic impacts.


Assuntos
Apoptose/efeitos dos fármacos , Dano ao DNA , Leite/fisiologia , Piretrinas/toxicidade , Testículo/efeitos dos fármacos , Animais , Antioxidantes/metabolismo , Camelus , Inseticidas/toxicidade , Masculino , Estresse Oxidativo/efeitos dos fármacos , Ratos , Testículo/enzimologia , Testículo/metabolismo , Testículo/patologia
11.
Int. j. morphol ; 37(2): 515-521, June 2019. tab, graf
Artigo em Inglês | LILACS | ID: biblio-1002253

RESUMO

SUMMARY: Reproductive dysfunction is a complication for many diseases and toxins. Its early diagnosis and treatment are immensely important. Here the morphological histoarchitecture changes in early testicular and cauda toxicity before and after treatment with angiotensin receptor blockers were evaluated. Low-grade testicular damage was induced using thioacetamide (TAA, 50 mg/kg/day) intraperitoneally for two weeks in rats. The rats were randomly divided into four groups (n = 8) treated daily orally for three weeks as follows: Normal control (distilled water), TAA (positive control), TAA+candesartan (0.2 mg/kg) and TAA+losartan (7.5 mg/kg). Serum testosterone and testicular malondialdehyde and glutathione were measured. The changes in histoarchitecture of testis and cauda epididymis were evaluated by hematoxylin and eosin for general structure, Masson's trichrome for collagen, periodic acid Schiff for basement membrane, and caspase-3 and proliferating cell nuclear antigen (PCNA) for immunohistochemical analysis. The TAA-rats showed decreases of serum testosterone and testicular glutathione, increases in testicular malondialdehyde, degenerative changes and apoptosis in germ cells, thickening of tubular basal lamina and increases in expression of caspase 3, and decreases in expression of PCNA. The ARBs (candesartan and losartan) significantly reversed these changes with non-significant differences in-between. Treatment with ARBs (candesartan and losartan) significantly reversed TAA-induced low-grade testicular and cauda toxicity in rats. This could be potentially useful for early treatment of male patients with occupational toxicant-induced reproductive dysfunction especially if they are using ARBs for other comorbidities.


RESUMEN: La disfunción reproductiva es una complicación por muchas enfermedades y toxinas. Su diagnóstico y tratamiento tempranos son inmensamente importantes. Aquí se evaluaron los cambios morfológicos en la histoarquitectura en la toxicidad precoz testicular y cauda antes y después del tratamiento con bloqueadores de receptores de angiotensina. Se indujo daño testicular de bajo grado usando tioacetamida (TAA, 50 mg / kg / día) por vía intraperitoneal durante dos semanas en ratas. Las ratas se dividieron aleatoriamente en cuatro grupos (n = 8) tratados diariamente por vía oral durante tres semanas de la siguiente manera: control normal (agua destilada), TAA (control positivo), TAA + candesartan (0,2 mg / kg) y TAA + losartán (7,5 mg / kg). Se midieron la testosterona sérica, el malondialdehído testicular y el glutatión. Los cambios en la histoarquitectura de los testículos y la epidermis de la cauda se evaluaron mediante Hematoxilina y Eosina para determinar la estructura general, con tricrómicro de Masson para el colágeno, ácido periódico de Schiff para la membrana basal y la caspasa-3 y el antígeno nuclear de células proliferantes (PCNA) para análisis inmunohistoquímico. Las ratas TAA mostraron disminución de la testosterona sérica y glutatión testicular, aumentos en el malondialdehído testicular, cambios degenerativos y apoptosis en células germinales, engrosamiento de la lámina basal tubular y aumentos en la expresión de la caspasa 3, y disminución en la expresión de PCNA. Los ARB (candesartán y losartán) revirtieron significativamente estos cambios con diferencias no significativas en el medio. El tratamiento con BRA (candesartán y losartán) revirtió significativamente la toxicidad testicular y cauda inducida por TAA en ratas. Esto podría ser potencialmente útil para el tratamiento temprano de pacientes con disfunción reproductiva inducida por tóxicos ocupacionales, especialmente si están usando BRA para otras comorbilidades.


Assuntos
Animais , Masculino , Ratos , Testículo/efeitos dos fármacos , Tioacetamida/toxicidade , Benzimidazóis/farmacologia , Losartan/farmacologia , Bloqueadores do Receptor Tipo 1 de Angiotensina II/farmacologia , Testículo/patologia , Testosterona/análise , Tetrazóis/farmacologia , Imuno-Histoquímica , Ratos Sprague-Dawley , Antígeno Nuclear de Célula em Proliferação/metabolismo , Caspase 3/metabolismo , Glutationa/análise , Malondialdeído/análise
12.
Zhongguo Ying Yong Sheng Li Xue Za Zhi ; 35(2): 145-149, 2019 Feb.
Artigo em Chinês | MEDLINE | ID: mdl-31250606

RESUMO

OBJECTIVE: To investigate the intervention of curcumin and its analogue J7 on oxidative stress injury in testis of type 2 diabetic rats. METHODS: Sixty male SD rats, 10 rats were chosen as normal control group (NC), the other 50 rats were assigned to experiment group. Experiment diabetic rats were induced by high-fat food and intraperitoneal injection of steptozotocin (STZ). After the model was established successfully, diabetic rats were divided into four groups randomly: diabetes mellitus group (DM, n=12), curcumin treatment group (CUR, n=10), high dose treatment group of J7 (J+, n=10), low dose treatment group of J7 (J-, n=10). The CUR group were intragastrically administered with curcumin 20 mg/kg daily, in addition, the J+ group and the J- group were intragastrically administered with J7 20 mg/kg and 10 mg/kg daily respectively. After 8 weeks, the fast blood glucose was detected biochemically. The activity of superoxide dismutase (SOD) and the level of malondialdehyde (MDA) were detected by hydroxylamine method and thiobarbituric acid method respectively. The protein expressions of the nuclear factor-erythroid 2-related factor 2 (tNrf2), phosphorylation of Nrf2 (pNrf2), catalase (CAT), NAD(P)H quinine oxidoreductase 1 (NQO1) were measured by Western blot. The mRNA expressions of CAT, NQO1, hemeoxygenase-1 (HO1) were measured by quantitative real-time PCR (qRT-PCR). Morphological structure of testis was observed by hematoxylin-eosin (HE) staining. The expressions of Nrf2 and CAT were also detected by immunohistochemical method. RESULTS: The levels of fast blood glucose and MDA in DM group were increased significantly(P<0.05), while the body weight, the activity of SOD, the protein expressions of pNrf2/tNrf2, CAT, NQO1 and the mRNA expressions of CAT, NQO1, HO1 were decreased (P<0.05). Under light microscope, the DM group showed disrupted histological appearance. Immunohistochemistry showed that the protein expressions of Nrf2 around the nucleus and CAT were decreased. With the treatment of curcumin and J7, the MDA levels in the three treatment groups were decreased (P<0.05). The activity of SOD, the protein expressions of pNrf2/tNrf2, CAT, NQO1 and the mRNA expressions of NQO1, HO1 were increased (P<0.05). the levels of fast blood glucose were decreased in the J+ and J- group (P<0.05), and the mRNA expression of CAT was increased in the J+ group (P<0.05). The ratio of pNrf2/tNrf2 in the J+ group was significantly higher than that in CUR and J- group (P<0.05). The protein level of CAT in the J+ group was also significantly higher than that in J- group (P<0.05). There were no significant differences in other indexes among the three treatment groups. Under light microscope, the morphology was obviously improved in the three treatment groups. Immunohistochemistry showed that the protein expressions of Nrf2 around the nucleus and CAT were increased in the three treatment groups. It was suggested that high dose J7 had better antioxidant stress ability in testis of diabetic rats. CONCLUSION: Curcumin and J7 could inhibit the oxidative stress damage of testicular tissue in diabetic rats, which might be related with the activation of the Nrf2-ARE signaling pathway.


Assuntos
Curcumina/farmacologia , Diabetes Mellitus Tipo 2 , Estresse Oxidativo , Testículo/efeitos dos fármacos , Animais , Glicemia/análise , Curcumina/análogos & derivados , Diabetes Mellitus Experimental , Masculino , Malondialdeído/metabolismo , Fator 2 Relacionado a NF-E2/metabolismo , Distribuição Aleatória , Ratos , Ratos Sprague-Dawley , Transdução de Sinais , Superóxido Dismutase/metabolismo , Testículo/patologia
13.
J Environ Sci Health B ; 54(7): 549-559, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31094287

RESUMO

This study assessed the long-term toxicity of chlorpyrifos on survival and reproduction of Banded Gourami by using mortality, gonado-somatic index (GSI) and histopathological observations as endpoints. Adult fish were exposed to five different concentrations of chlorpyrifos (0, 15, 50, 150, 500 µg/L) in 15 PVC tanks for 15, 30, 45, 60 and 75 days. Results showed that all male and female fish died after 15 days of 500 µg/L chlorpyrifos exposure. No consistent significant effect was observed for both male and female GSI. Furthermore, results showed dose- and time-dependent histopathological alterations for both ovary and testes. The 60-d No Observed Effect Concentration (NOEC) for most histopathological alterations of Banded Gourami ovary and testes was 50 µg/L, while 60-d NOEC for mortality of both male and female fish was < 15 µg/L. The results show that the long-term exposure to chlorpyrifos not only affect the reproductive tissues of Banded Gourami at exposure concentrations but also cause their mortality. Future studies should evaluate effects at lower concentrations.


Assuntos
Clorpirifos/toxicidade , Perciformes/fisiologia , Poluentes Químicos da Água/toxicidade , Animais , Relação Dose-Resposta a Droga , Feminino , Masculino , Mortalidade , Ovário/efeitos dos fármacos , Ovário/patologia , Reprodução/efeitos dos fármacos , Testículo/efeitos dos fármacos , Testículo/patologia
14.
Environ Pollut ; 251: 372-379, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31091501

RESUMO

T-2 toxin is an unavoidable contaminant in human food, animal feeds, and agricultural products. T-2 toxin has been found to impair male reproductive function. But, few data is available that reveals the reproductive toxicity mechanism. In the study, male Kunming mice were orally administrated with T-2 toxin at the doses of 0, 0.5, 1 or 2 mg/kg body weight for 28 days. The body and reproductive organs weight, the concentration, malformation rate and ultrastructure of sperm in cauda epididymis were detected. Oxidative stress biomarkers and apoptosis were also measured in testes. Histological change of testes was performed by H&E and TUNEL staining. T-2 toxin down-regulated body and reproductive organs (testis, epididymis and seminal vesicle) weight, sperm concentration, increased sperm malformation rate and damaged the ultrastructure of sperm and structure of testes. T-2 toxin treatment increased the reactive oxygen species (ROS) and malondialdehyde content, while, decreased the total anti-oxidation capacity (T-AOC) and the superoxide dismutase activity in testes. T-2 toxin exposure increased the TUNEL-positive germ cells, the activities and mRNA expressions of caspase-3, caspase-8 and caspase-9, the mRNA expression of Bax, and inhibited the Bcl-2 mRNA expression. Furthermore, the expressions of caspase-3, caspase-8 caspase-9 and Bax were positively correlated with ROS level, but negatively correlated with T-AOC in testis. In summary, T-2 toxin caused spermatogenesis disorder associated with the germ cell apoptosis medicated by oxidative stress, impairing the male reproductive function.


Assuntos
Apoptose/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Espermatogênese/efeitos dos fármacos , Espermatozoides/patologia , Toxina T-2/toxicidade , Animais , Apoptose/genética , Epididimo/efeitos dos fármacos , Epididimo/patologia , Epididimo/fisiopatologia , Masculino , Camundongos , Espermatozoides/efeitos dos fármacos , Espermatozoides/metabolismo , Espermatozoides/ultraestrutura , Testículo/efeitos dos fármacos , Testículo/patologia , Testículo/fisiopatologia
15.
Food Chem ; 294: 1-8, 2019 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-31126441

RESUMO

The effects of hazelnut supplemented diet on the reproductive system of young and old male rats were investigated. Young male rats were grouped into young control group (YCG) and young hazelnut group (YHG). Old male rats were grouped into old control group (OCG), old hazelnut group (OHG), and old vitamin E group (OEG). While YCG and OCG were given rat feed, YHG and OHG were given rat feed supplemented with hazelnut (3 g/kg body weight). OEG was subjected to rat feed and administered vitamin E (50 mg/kg body weight). When YCG and OCG were compared, aging increased histopathological damage and decreased sperm quality. Hazelnut supplemented diet improved histopathological variables, sperm quality, seminal plasma and plasma oxidative stress, seminal plasma vitamin E, and plasma testosterone levels in both groups. The present work suggests that hazelnut supplemented diet significantly improves testicular antioxidant function and semen quality in old male rats.


Assuntos
Corylus/química , Suplementos Nutricionais , Espermatozoides/fisiologia , Animais , Antioxidantes/química , Corylus/metabolismo , Masculino , Nozes/química , Nozes/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Ratos , Ratos Sprague-Dawley , Sêmen/efeitos dos fármacos , Sêmen/fisiologia , Espermatozoides/efeitos dos fármacos , Testículo/patologia , Testosterona/sangue , Vitamina E/farmacologia
16.
Eur J Med Chem ; 176: 21-40, 2019 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-31091478

RESUMO

Male late-onset hypogonadism (LOH) is reported as one of the most common age-related diseases occurred in middle-aging men. Testosterone replacement therapy (TRT) is currently the main clinical treatment for LOH, however it has obvious side effects. A 2-methylpyrimidine-fused tricyclic diterpene analog 7 was afforded as anti-LOH hit, which was screened out from our small synthetic library. Then a series of derivates were designed and synthesized based on the hit and their effects in promoting testosterone production and cytotoxicities were evaluated in mouse TM3 Leydig cells. The most potent and safe compound 29 (SH379) was obtained, which significantly promoted the expression of the key testosterone synthesis-related enzymes StAR and 3ß-HSD. Further studies discovered that 29 could stimulate autophagy through regulating AMPK/mTOR signaling pathway. More importantly, 29 increased the testosterone levels and the sperm viability and motility in PADAM (partial androgen deficiency in aging males) rats obviously and displayed almost no side effects. Furthermore, Preliminary pharmacokinetics evaluation also indicated an excellent oral bioavailability of 29. Therefore, these methylpyrimidine-fused tricyclic diterpene analogs could be used as leads for the development of a new type of potential anti-LOH agent.


Assuntos
Diterpenos/uso terapêutico , Hipogonadismo/tratamento farmacológico , Pirimidinas/uso terapêutico , Testosterona/metabolismo , 3-Hidroxiesteroide Desidrogenases/metabolismo , Administração Oral , Animais , Linhagem Celular , Diterpenos/administração & dosagem , Diterpenos/síntese química , Diterpenos/toxicidade , Humanos , Masculino , Camundongos , Estrutura Molecular , Fosfoproteínas/metabolismo , Pirimidinas/administração & dosagem , Pirimidinas/síntese química , Pirimidinas/toxicidade , Ratos Sprague-Dawley , Glândulas Seminais/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Relação Estrutura-Atividade , Testículo/efeitos dos fármacos , Testículo/patologia
17.
Chemosphere ; 230: 327-336, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31108444

RESUMO

Furan is a colorless toxic chemical produced in various food items during heat processing and in chemical industries. Both in vitro and in vivo studies have reported that it induces oxidative stress and endocrine disruption; however, limited data are available regarding the effects of furan on the reproduction of mammals. In the present study, an in vitro experiment was designed to investigate the direct effects of furan exposure on oxidative stress and testosterone concentration in rat testicular tissue. Furan not only generated high oxidative stress but also decreased antioxidant enzyme activity in the testicular tissue. On the basis of in vitro study results, an in vivo sub-chronic exposure study was performed. Male rats were orally exposed to different concentrations of furan (0, 5, 10, 20, and 40 mg kg-1). An increase (P < 0.05) of reactive oxygen species (ROS) and of the lipid profile (cholesterol, triglycerides, and LDL) in higher dose treatment groups of furan was observed, while total protein content and antioxidant enzyme activity were considerably decreased after furan exposure. Also, plasma and intratesticular testosterone concentrations were reduced in high-dose treatment groups. Sperm parameters such as sperm viability, sperm count, and sperm motility showed a decrease (P < 0.05) in a dose-dependent manner. Histopathological findings revealed significant alterations in testis and epididymis tissues. These results confirm that furan can induce toxic effects on the reproductive system of male rats.


Assuntos
Disruptores Endócrinos/toxicidade , Furanos/toxicidade , Estresse Oxidativo/efeitos dos fármacos , Espermatozoides/efeitos dos fármacos , Testículo/efeitos dos fármacos , Testosterona/sangue , Animais , Antioxidantes/metabolismo , Relação Dose-Resposta a Droga , Técnicas In Vitro , Masculino , Ratos , Ratos Wistar , Espécies Reativas de Oxigênio/metabolismo , Contagem de Espermatozoides , Motilidade Espermática/efeitos dos fármacos , Testículo/enzimologia , Testículo/patologia , Testes de Toxicidade Subcrônica
18.
Croat Med J ; 60(2): 158-165, 2019 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-31044589

RESUMO

AIM: To analyze the differences in the population of perivascular and peritubular Leydig cells (LC) and the number of Reinke's crystals (RCs) in the testicles of infertile men with non-obstructive and obstructive azoospermia. METHODS: This retrospective case-control study was conducted on the testicle tissue of infertile men with obstructive (n=10) and those with non-obstructive azoospermia (n=100). Stereological analysis was performed on 7-µm paraffin sections. Measurements were carried out by using the Weibel multipurpose test system. RESULTS: Patients with non-obstructive azoospermia had a higher total/absolute number of LCs in the perivascular space (P=0.034). In these patients, no significant difference was found in the total and absolute number of RCs between the peritubular and perivascular space. Patients with obstructive azoospermia had around three times higher absolute number of RCs in both the peritubular and perivascular spaces (P=0.002; P<0.001) than non-obstructive group. CONCLUSION: Our results suggest that in patients with non-obstructive azoospermia LCs migrated or had different densities in the peritubular and perivascular space compared with patients with obstructive azoospermia. Moreover, the lower number of RCs could imply their utilization by LCs in testosterone production.


Assuntos
Azoospermia/patologia , Células Intersticiais do Testículo/patologia , Testículo/patologia , Adulto , Estudos de Casos e Controles , Cristalização , Humanos , Masculino , Estudos Retrospectivos
20.
Environ Toxicol ; 34(8): 968-978, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31077554

RESUMO

The aim of this study was to investigate the protective effects of Nano-Se against Ni-induced testosterone synthesis disorder in rats and determine the underlying protective mechanism. Sprague-Dawley rats were co-treated with Ni (5.0 mg/kg, i.p.) and Nano-Se (0.5, 1.0, and 2.0 mg/kg, oral gavage) for 14 days after which various endpoints were evaluated. The Ni-induced abnormal pathological changes and elevated 8-OHdG levels in the testes were attenuated by Nano-Se administration. Importantly, decreased serum testosterone levels in the Ni-treated rats were significantly restored by Nano-Se treatment, particularly at 1.0 and 2.0 mg/kg. Furthermore, the mRNA and protein levels of testosterone synthetase were increased by Nano-Se compared to the Ni group, whereas phosphorylated protein expression levels of mitogen-activated protein kinase (MAPK) pathways were suppressed by Nano-Se administration in the Ni-treated rats. Overall, the results suggest that Nano-Se may ameliorate the Ni-induced testosterone synthesis disturbance via the inhibition of ERK1/2, p38, and JNK MAPK pathways.


Assuntos
Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Níquel/toxicidade , Selênio/farmacologia , Testosterona/biossíntese , Animais , MAP Quinases Reguladas por Sinal Extracelular/antagonistas & inibidores , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Proteínas Quinases JNK Ativadas por Mitógeno/antagonistas & inibidores , Proteínas Quinases JNK Ativadas por Mitógeno/metabolismo , Masculino , Nanopartículas , Fosforilação/efeitos dos fármacos , Ratos , Ratos Sprague-Dawley , Testículo/efeitos dos fármacos , Testículo/metabolismo , Testículo/patologia , Testosterona/sangue , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo
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