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Leydig cell toxicity

Cinthia Dos S Alves, Humberto V Frias, Thiago B Kirsten, Flora Cordeiro, Maria M Bernardi, Ivana B Suffredini
ETHNOPHARMACOLOGICAL RELEVANCE: Luffa operculata (L.) Cogn., Cucurbitaceae (buchinha-do-norte), aqueous extract (EBN) is popularly used to relieve symptoms of sinusitis and as abortive. AIM OF THE STUDY: As neurotoxicity and toxicity studies on the male reproductive system are scarce, the present study aimed at quantitatively addressing the question. MATERIALS AND METHODS: Male adult rats were observed in the open field (OF) and in the light-dark box test (LDB) to evaluate locomotion and anxiety...
May 1, 2018: Journal of Ethnopharmacology
Yiyan Wang, Shengsong Huang, Zhao Wang, Fenfen Chen, Panpan Chen, Xingxing Zhao, Han Lin, Renshan Ge, Barry Zirkin, Haolin Chen
The inability of cultured primary Leydig cells to maintain luteinizing hormone (LH)-responsive testosterone formation in vitro for more than 3-5 days has presented a major challenge in testing trophic effects of regulatory factors or environmental toxicants. Our primary objective was to establish culture conditions sufficient to maintain LH-responsive testosterone formation by Leydig cells for at least a month. When isolated rat adult Leydig cells were cultured in DMEM/F12 and M199 culture medium containing insulin (10μg/ml), PDGFAA (10 ng/ml), lipoprotein (0...
April 24, 2018: Molecular and Cellular Endocrinology
F Beyazal Celiker, L Tumkaya, T Mercantepe, G Turan, A Yılmaz, M Beyazal, A Turan, M F Inecikli, M Kösem
Previous studies have reported that repeated administrations of linear gadolinium-based contrast agents lead to their accumulation in the brain and other tissues in individuals with normal renal functions. The purpose of this prospective animal study was to investigate the effect of multiple administrations of macrocyclic ionic (gadoteric acid) and linear nonionic (gadodiamide) gadolinium-based contrast agents (GBCAs) on rat testis tissue and to compare these molecules in terms of tissue damage. Thirty-two male Sprague-Dawley rats were kept without drugs for 5 weeks after administration of 0...
April 26, 2018: Andrologia
Jonathan T Haselman, Patricia A Kosian, Joseph J Korte, Allen W Olmstead, Sigmund J Degitz
The Larval Amphibian Growth and Development Assay (LAGDA) is an internationally harmonized testing guideline for evaluating effects of chronic chemical exposure in amphibians. In order to evaluate the effects of chronic exposure to an antiandrogenic chemical in an amphibian model, prochloraz was tested using a variation of the LAGDA design. Exposure was initiated with <1d post-fertilization embryos at nominal concentrations of 0, 6.7, 20, 60 and 180 μg/L (0, 18, 53, 159, 478 nM) and continued in flow-through conditions until two months following the median time that controls completed metamorphosis...
April 3, 2018: Aquatic Toxicology
Xiangliang Tang, Shengde Wu, Lianju Shen, Yi Wei, Xining Cao, Yangcai Wang, Chunlan Long, Yue Zhou, Dian Li, Fangyuan Huang, Bo Liu, Guanghui Wei
Di-(2-ethylhexyl) phthalate (DEHP) is an environmental endocrine disruptor widely used in China that is harmful to the male reproductive system. Many studies have shown that DEHP causes testicular toxicity through oxidative stress, but the specific mechanism is unknown. Because the Notch pathway is a key mechanism for regulating cell growth and proliferation, we investigated whether Notch is involved in DEHP-induced testicular toxicity and whether vitamins E and C could rescue testicular impairment in Sprague-Dawley (SD) rats...
April 16, 2018: Environmental Toxicology
Amany Tharwat Mohammed, Lamiaa L M Ebraheim, Mohamed M M Metwally
Ebselen (EBS) is a versatile compound that can protect the cellular components from oxidative and free radical-mediated damage. In the present study, we investigated the protective effect of EBS against manganese (Mn) toxicity on male reproductive organs. Thirty-two male rats were assigned into four groups, namely, negative control, EBS (15 mg/kg body weight (bw), as a single protective IP injection), MnCl2 (50 mg/kg bw, orally for 30 consecutive days), and EBS + MnCl2 (as mentioned before). The results showed that EBS ameliorated the alterations caused by MnCl2 in the testicular, epididymal, and seminal vesicle tissues...
March 28, 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
Cornelius Rimayi, David Odusanya, Jana M Weiss, Jacob de Boer, Luke Chimuka, Felix Mbajiorgu
Sub-chronic toxicity of environmentally relevant atrazine concentrations on exposed tadpoles and adult male African clawed frogs (Xenopus laevis) was evaluated in a quality controlled laboratory for 90 days. The aim of this study was to determine the effects of atrazine on the survival, growth and gonad development of African clawed frogs. After exposure of tadpoles to atrazine concentrations of 0 (control), 0.01, 200 and 500 μg L-1 in water, mortality rates of 0, 0, 3.3 and 70% respectively were recorded for the 90 day exposure period...
March 23, 2018: Aquatic Toxicology
Fu-Chi Kang, Shu-Chun Wang, Ming-Min Chang, Bo-Syong Pan, Kar-Lok Wong, Ka-Shun Cheng, Edmund Cheung So, Bu-Miin Huang
Background: Midazolam (MDZ) has powerful hypnosis, amnesia, anti-anxiety and anticonvulsant effects. Studies have shown that prenatally developmental toxicity of diazepam can be observed in many organs/tissues. However, it remains elusive in male reproductive system. Materials and methods: TM3 mouse Leydig progenitor cell line was used to determine whether MDZ has any unfavorable effects. Results: Midazolam significantly decreased cell viability in dose- and time-dependent manners in TM3 cells...
2018: OncoTargets and Therapy
Yixing Feng, Jiachen Shi, Zhihao Jiao, Hejun Duan, Bing Shao
Bisphenol AF (BPAF) has been shown to inhibit testicular steroidogenesis in male rats. However, the precise mechanisms related to the toxic effects of BPAF on reproduction remain poorly understood. In the present study, a mouse Leydig tumor cell line (mLTC-1) was used as a model to investigate the mechanism of steroidogenic inhibition and to identify the molecular target of BPAF. Levels of progesterone and the concentration of cyclic adenosine monophosphate (cAMP) in cells exposed to BPAF were detected, and expression of key genes and proteins in steroid biosynthesis was assessed...
March 25, 2018: Environmental Toxicology
Jianxia Sun, Mingwei Li, Feiyan Zou, Shun Bai, Xinwei Jiang, Lingmin Tian, Shiyi Ou, Rui Jiao, Weibin Bai
Acrylamide (AA) occurs in many cooked carbohydrate-rich foods and has caused widespread concern as a possible carcinogen. Glycidamide (GA) is the ultimate genotoxic metabolite of AA. The present study was to investigate the protective effect of Cyanidin-3-O-glucoside (C3G) against AA- and GA-induced reproductive toxicity in R2C Leydig cells. The results demonstrated that C3G inhibited AA- and GA-induced cytotoxicity and mitochondria-mediated cell apoptosis, the effective doses of C3G were ranging from 10 to 50 μM...
March 21, 2018: Food and Chemical Toxicology
Tolga Mercantepe, Deniz Unal, Levent Tümkaya, Zihni Acar Yazici
Cisplatin is an effective antineoplastic drug that is usually used to treat a number of different types of cancer in the clinic. One of the most notable side effects of cisplatin use is infertility. The present study was designed to determine the non-oxidative testicular effects caused by the use of cisplatin in rats. The rats were randomly allocated to the experimental groups. The untreated rats represented the control group (group I) and the treatment groups were as follows: cisplatin alone (group II), cisplatin+amifostine (group III), cisplatin+curcumin (group IV), and cisplatin+caffeic acid phenethyl ester (CAPE; group V)...
April 2018: Experimental and Therapeutic Medicine
Hyun-Kyoung Kim, Raj Kumar Yadav, Kashi Raj Bhattarai, Han-Wool Jung, Hyung-Ryong Kim, Han-Jung Chae
STUDY QUESTION: Is the Transmembrane BAX Inhibitor Motif-6 (TMBIM6) involved in the molecular mechanism by which cisplatin causes reproductive toxicity? SUMMARY ANSWER: TMBIM6 protects against cisplatin-induced testicular toxicity through up-regulation of heme oxygenase-1 (HO-1),-which maintains the levels of steroidogenic enzymes by decreaseing oxidative stress in the endoplasmic reticulum (ER). WHAT IS KNOWN ALREADY: Testosterone production is highly suppressed as a main complication of cisplatin (cis-diamminedichloroplatinum) anticancer therapy...
January 4, 2018: Human Reproduction
Ukpai A Eze, John Huntriss, Michael N Routledge, Yun Yun Gong
Epidemiological studies show that there is global decline in male fertility primarily as a result of poor sperm quality and this is attributed to exposure to endocrine disrupting chemicals (EDCs) in the environment, food and pharmaceutical products, including mycotoxins and pesticides. The Leydig cells in the male testes are responsible for producing androgens, hormones that play major roles in male development and reproductive function. Therefore, any toxin that affects the function and morphology of the Leydig cells may result in sub-fertility or infertility...
April 2018: Toxicology in Vitro: An International Journal Published in Association with BIBRA
Mei Wang, Ping Su
The Fas/FasL signaling pathway is one of the major pathways that regulate apoptosis. Increasing studies have shown that the activation of the Fas/FasL signaling pathway is closely associated with testicular cell apoptosis. However, the mechanism involved is still unclear. We discuss recent findings regarding the molecular mechanisms by which environmental toxicants induce testicular pathology via Fas/FasL signaling. These findings suggest that Fas/FasL signaling is employed to impact the sensitivity (a response to external factors) of germ cells, disrupt steroidogenic hormone and cytokine metabolism mediated by Sertoli cells, and elicit the activation of NFAT (nuclear factor of activated T-cells) in Leydig cell apoptosis...
April 2018: Systems Biology in Reproductive Medicine
Gessica Dutra Gonçalves, Simone Cristine Semprebon, Bruna Isabela Biazi, Mario Sergio Mantovani, Glaura Scantamburlo Alves Fernandes
Leydig cells are the major testosterone-producing cells of the male reproductive system, and damage to these cells can impair fertility of men. Bisphenol A (BPA) is one of the chemicals with the highest volume of production worldwide. The aim of this study was to evaluate the effects of BPA on the growth, viability, and testosterone production of TM3 murine Leydig cells after exposure to BPA for 24 or 48 h. BPA reduced testosterone production, cell viability and cell growth in a concentration-dependent manner...
March 2018: Reproductive Toxicology
Dibyendu Dutta, In Park, Hiwot Guililat, Samuel Sang, Arpita Talapatra, Barkha Singhal, Nathaniel C Mills
OBJECTIVE: Testosterone depletion induces increased germ cell apoptosis in testes. However, limited studies exist on genes that regulate the germ cell apoptosis. Granzymes (GZM) are serine proteases that induce apoptosis in various tissues. Multiple granzymes, including GZMA, GZMB and GZMN, are present in testes. Th us, we investigated which granzyme may be testosterone responsive and possibly may have a role in germ cell apoptosis aft er testosterone depletion. METHODS: Ethylene dimethane sulfonate (EDS), a toxicant that selectively ablates the Leydig cells, was injected into rats to withdraw the testosterone...
October 26, 2017: Endocrine Regulations
Majid Askaripour, Azam Hasanpour, Foruzan Hosseini, Mojgan Moshrefi, Gholamreza Moshtaghi, Mohammad Hasannejad, Soodeh Rajabi, Seyed Noureddin Nematollahi-Mahani
CONTEXT: Rosa damascena L. (Rosaceae) (RD) essential oil and extracts are commonly used as a flavour in herbal medicine which increase libido. Previous studies have shown inhalation of RD flower's oil increases libido and causes protective effects in formaldehyde (FA)-induced testicular damage. OBJECTIVE: The protective effects of aqueous extract of RD on the male reproductive system of mice were examined following FA-induced damage. MATERIALS AND METHODS: Forty-eight adult NMRI male mice were randomly assigned to six groups (n = 8): control (normal saline, 10 mg/kg); RD40 (40 mg/kg, p...
December 2018: Pharmaceutical Biology
O O Ogedengbe, A I Jegede, I O Onanuga, U Offor, A I Peter, E N Akang, E C S Naidu, O O Azu
The effects of Virgin coconut oil as an adjuvant to highly active antiretroviral therapy (HAART) were investigated on the testicular ultrastructure and biochemical markers in rats. Twenty male Sprague-Dawley rats, weighing 153-169 g were divided into four groups and treated as follows: control A (distilled water), B (HAART), C (HAART+Virgin coconut oil 10 ml/kg) and D (Virgin coconut oil [VCO] 10 ml/kg). Testicular segments were evaluated using transmission electron microscopy. Serum was assayed for testosterone, luteinising hormone, follicle stimulating hormone and testicular tissue for malondialdehyde and glutathione...
April 2018: Andrologia
Mariana Tilinca, Adrian Florea
In this study, we aimed to investigate the testicular toxicity of two molecules derived from bee venom (BV): phospholipase A2 (PlA2) and melittin (Mlt). Ultrastructural effects of purified BV PlA2 and Mlt were assessed consecutive to repeated dose (30 days) and acute toxicity studies. For the subchronic treatment, PlA2 and Mlt were injected in daily doses equivalent to those released by a bee sting (105 μg PlA2/kg/day and 350 μg Mlt/kg/day), while in the acute treatment their doses corresponded to those released by 100 bee stings (9...
January 2018: Toxicon: Official Journal of the International Society on Toxinology
Costantine Albany, Lawrence Einhorn, Lawrence Garbo, Thomas Boyd, Neil Josephson, Darren R Feldman
BACKGROUND: Cytotoxic therapy for relapsed and refractory germ cell tumors or metastatic sex cord stromal tumors is rarely effective and is often accompanied by high adverse event rates. Expression of CD30 has been observed in testicular cancers, and patients with CD30-expressing embryonal carcinomas have worse progression-free survival and overall survival than those with CD30-negative tumors. The objective of this study (NCT01461538) was to characterize the antitumor activity of brentuximab vedotin in patients with CD30-expressing nonlymphomatous malignancies...
March 2018: Oncologist
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