Arsenic trioxide (As2O3) poisoning and associated potential lesions are of a global concern. Inversely, riboflavin (vitamin B2, VB2) as a component of flavoproteins could play a vital role in the spermatogenic enzymatic reactions. Thus, this research aimed to explore potential beneficial roles of VB2 during As2O3-injured-toxicity. Rats were randomly allocated into 4 groups (n=8/group) and challenged as follows (for 30 days continuously): Group 1 received normal saline; Group 2 was treated with 3 mg As2O3/L; Group 3 received 40 mg VB2/L; Group 4 received 3 mg As2O3/L + 40 mg VB2/L. Both As2O3 and VB2 were dissolved in deionized water. Malondialdehyde (MDA), Glutathione Peroxidase (GSH-Px), Superoxide dismutase (SOD), and Catalase (CAT) were assessed for the oxidative profile, while TAS (Total Antioxidative Status) levels were evaluated for the antioxidant system, in both serum and testicular tissue. P<0.05 was considered statistically significant. The results show that As2O3 significantly decreased the body weight, testicular weight and testis volume, semen quality and testicular cell count (p<0.05). Furthermore, MDA content in the testicular tissue of the As2O3 group rats was significantly higher in comparison to the vehicle group (p<0.05). Likewise, TAS and the activities of GSH-Px, CAT and SOD were reduced (p<0.05) when compared to the control. As(2)O(3) induced testicular damage and seminiferous tubular atrophy. Monodansylcadaverine assays mirrored the histopathology observations. Meanwhile, As2O3 upregulated the expression of mitophagy-related genes including PINK1, Parkin, USP8, LC3-I, Fis1 and Mfn2. The p38 gene, responsible to stress stimuli, was also upregulated by As2O3 administration. Meanwhile, exposure to VB2 led to a significant decrease of the expression levels of mitophagy related genes. Our study revealed that VB2 supplementation protected testicular structures against As2O3-induced injury via a dual inhibition of oxidative changes and a regulation of the PINK1-mediated pathway.
- MeSH
- antioxidancia farmakologie MeSH
- mitofagie účinky léků MeSH
- oxid arsenitý toxicita MeSH
- oxidační stres účinky léků MeSH
- potkani Wistar MeSH
- proteinkinasy genetika metabolismus MeSH
- proteiny spojené s autofagií genetika metabolismus MeSH
- riboflavin farmakologie MeSH
- signální transdukce MeSH
- spermatogeneze účinky léků MeSH
- spermie účinky léků enzymologie patologie MeSH
- testis účinky léků enzymologie patologie MeSH
- zvířata MeSH
- Check Tag
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
Fruit of Terminalia chebula Retz. (Combretaceae) has male contraceptive folk medicine reputation but its molecular aspect regarding hypotesticular activity is still in dark. The study focused the hypotesticular efficacy of the most potent fraction out of n-hexane, chloroform and ethyl acetate fractions of hydro-methanolic (3:2) extract of Terminalia chebula in connection with male herbal contraceptive development. Treatment with above fractions of Terminalia chebula showed a significant diminution in the activities of androgenic key enzymes (Δ5, 3β-HSD, 17β-HSD) and inhibition in serum testosterone level in compare to the control. Significant up regulation of testicular Bax gene and down regulation of Bcl-2 gene indicated the hypotesticular activity of these fractions. Flow-cytometric study focused a significant diminution in sperm viability and sperm mitochondrial status after the treatment with different fractions. Out of these, ethyl acetate fraction showed most promising hypotesticular effect without impairing any toxicity in general which highlighted that the fraction may contains antitesticular agent(s) in threshold levels compare to other fractions as it decreases spermiological, testicular genomic sensors and elevates sperm apoptotic sensors that may lead to male contraception.
- MeSH
- látky blokující spermatogenezi * chemie izolace a purifikace MeSH
- modely u zvířat MeSH
- potkani Wistar MeSH
- průtoková cytometrie MeSH
- rostlinné extrakty MeSH
- spermie účinky léků MeSH
- Terminalia chemie MeSH
- testis enzymologie chemie účinky léků MeSH
- zvířata MeSH
- Check Tag
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- práce podpořená grantem MeSH
Numerous chemicals in the environment have the ability to interact with the endocrine system. These compounds are called endocrine disruptors (EDs). Exposure to EDs represents one of the hypotheses for decreasing fertility, the increased risk of numerous cancers and obesity, metabolic syndrome and type 2 diabetes. There are various mechanisms of ED action, one of which is their interference in the action of 11β-hydroxysteroid dehydrogenase (11βHSD) that maintains a balance between active and inactive glucocorticoids on the intracellular level. This enzyme has two isoforms and is expressed in various tissues. Inhibition of 11βHSD in various tissues can have different consequences. In the case of EDs, the results of exposure are mainly adverse; on the other hand pharmaceutically developed inhibitors of 11βHSD type 1 are evaluated as an option for treating metabolic syndrome, as well as related diseases and depressive disorders. This review focuses on the effects of 11βHSD inhibitors in the testis, colon, adipose tissue, kidney, brain and placenta.
- MeSH
- 11-beta-hydroxysteroiddehydrogenasa typ 1 antagonisté a inhibitory metabolismus MeSH
- 11-beta-hydroxysteroiddehydrogenasa typ 2 antagonisté a inhibitory metabolismus MeSH
- diabetes mellitus chemicky indukované enzymologie patologie MeSH
- endokrinní disruptory farmakologie MeSH
- glukokortikoidy metabolismus MeSH
- inhibitory enzymů farmakologie MeSH
- kolon účinky léků enzymologie MeSH
- lidé MeSH
- metabolický syndrom chemicky indukované enzymologie patologie MeSH
- mozek účinky léků enzymologie MeSH
- nádory chemicky indukované enzymologie patologie MeSH
- obezita chemicky indukované enzymologie patologie MeSH
- orgánová specificita MeSH
- placenta účinky léků enzymologie MeSH
- těhotenství MeSH
- testis účinky léků enzymologie MeSH
- tuková tkáň účinky léků enzymologie MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- těhotenství MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- přehledy MeSH
Dehydrogenase/reductase (SDR family) member 3 (DHRS3), also known as retinal short-chain dehydrogenase/reductase (retSDR1) is a member of SDR16C family. This family is thought to be NADP(H) dependent and to have multiple substrates; however, to date, only all-trans-retinal has been identified as a DHRS3 substrate. The reductive reaction catalysed by DHRS3 seems to be physiological, and recent studies proved the importance of DHRS3 for maintaining suitable retinoic acid levels during embryonic development in vivo. Although it seems that DHRS3 is an important protein, knowledge of the protein and its properties is quite limited, with the majority of information being more than 15 years old. This study aimed to generate a more comprehensive characterisation of the DHRS3 protein. Recombinant enzyme was prepared and demonstrated to be a microsomal, integral-membrane protein with the C-terminus oriented towards the cytosol, consistent with its preference of NADPH as a cofactor. It was determined that DHRS3 also participates in the metabolism of other endogenous compounds, such as androstenedione, estrone, and DL-glyceraldehyde, and in the biotransformation of xenobiotics (e.g., NNK and acetohexamide) in addition to all-trans-retinal. Purified and reconstituted enzyme was prepared for the first time and will be used for further studies. Expression of DHRS3 was shown at the level of both mRNA and protein in the human liver, testis and small intestine. This new information could open other areas of DHRS3 protein research.
- MeSH
- alkoholoxidoreduktasy metabolismus MeSH
- cytosol metabolismus MeSH
- jaterní mikrozomy enzymologie metabolismus MeSH
- játra enzymologie metabolismus MeSH
- lidé MeSH
- membránové proteiny metabolismus MeSH
- NADH, NADPH oxidoreduktasy metabolismus MeSH
- NADP metabolismus MeSH
- Sf9 buňky MeSH
- Spodoptera metabolismus MeSH
- syntázy mastných kyselin metabolismus MeSH
- tenké střevo enzymologie metabolismus MeSH
- testis enzymologie metabolismus MeSH
- tretinoin metabolismus MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
The aim of this study was to investigate the protective effect of naringenin on oxidative stress, on proinflammatory cytokines like TGF-beta1, IL-1beta and on programmed cell death in the testicular damage resulting from streptozotocin (STZ) induced diabetes in rats. Diabetes was induced by a single intraperitoneal injection of STZ (50 mg/kg), and the rats were treated with naringenin (5 mg/kg and 10 mg/kg) administered once a day orally for 10 weeks, starting 3 days after the STZ injection. At the end of the study, all animals were sacrificed. Testis tissue and blood samples were collected for the assessment of sperm parameters, and for biochemical and histopathological analysis. Naringenin treatment significantly decreased the levels of elevated tissue TBARS (thio-barbituric acid) and increased the superoxide dismutase (SOD), catalase and glutathione peroxidase (GPx) enzyme activities in the testis tissues. The naringenin-treated rats in the diabetic group showed an improved histological appearance, sperm parameters, and serum testosterone levels, along with a decrement of terminal dUTP nick end-labeling (TUNEL) detected program cell death and a reduced over expression of TGF-beta1, IL-1beta in Sertoli cells and Leydig cells. These results suggest that naringenin is a food supplement potentially beneficial in reducing testicular damage in diabetic rats by decreasing the oxidative stress related to programmed cell death.
- MeSH
- antagonisté estrogenu aplikace a dávkování farmakologie MeSH
- apoptóza účinky léků MeSH
- experimentální diabetes mellitus * farmakoterapie krev MeSH
- flavanony * aplikace a dávkování farmakologie MeSH
- imunohistochemie MeSH
- interleukin-1beta MeSH
- motilita spermií účinky léků MeSH
- oxidační stres účinky léků MeSH
- počet spermií statistika a číselné údaje MeSH
- potkani Wistar MeSH
- rastrovací tunelová mikroskopie MeSH
- statistika jako téma MeSH
- studie případů a kontrol MeSH
- testis * enzymologie imunologie patologie MeSH
- testosteron krev MeSH
- transformující růstový faktor beta1 MeSH
- zárodečné buňky účinky léků MeSH
- zvířata MeSH
- Check Tag
- mužské pohlaví MeSH
- zvířata MeSH
- MeSH
- androgeny izolace a purifikace metabolismus MeSH
- antimülleriánský hormon * dějiny izolace a purifikace metabolismus MeSH
- gonadotropiny hypofyzární metabolismus MeSH
- inzulinová rezistence * MeSH
- Leydigovy buňky enzymologie účinky léků MeSH
- lidé MeSH
- plod enzymologie metabolismus účinky léků MeSH
- Sertoliho buňky fyziologie účinky léků MeSH
- spermatogeneze fyziologie účinky léků MeSH
- statistika jako téma MeSH
- syndrom polycystických ovarií diagnóza enzymologie metabolismus MeSH
- testis enzymologie růst a vývoj MeSH
- věkové faktory * MeSH
- Check Tag
- lidé MeSH
Speciation genes restrict gene flow between the incipient species and related taxa. Three decades ago, we mapped a mammalian speciation gene, hybrid sterility 1 (Hst1), in the intersubspecific hybrids of house mouse. Here, we identify this gene as Prdm9, encoding a histone H3 lysine 4 trimethyltransferase. We rescued infertility in male hybrids with bacterial artificial chromosomes carrying Prdm9 from a strain with the "fertility" Hst1(f) allele. Sterile hybrids display down-regulated microrchidia 2B (Morc2b) and fail to compartmentalize gammaH2AX into the pachynema sex (XY) body. These defects, seen also in Prdm9-null mutants, are rescued by the Prdm9 transgene. Identification of a vertebrate hybrid sterility gene reveals a role for epigenetics in speciation and opens a window to a hybrid sterility gene network.
- MeSH
- epigeneze genetická MeSH
- financování organizované MeSH
- histonlysin-N-methyltransferasa genetika chemie metabolismus MeSH
- histony metabolismus MeSH
- hybridizace genetická MeSH
- křížení genetické MeSH
- mapování chromozomů MeSH
- meióza MeSH
- metylace MeSH
- molekulární sekvence - údaje MeSH
- mužská infertilita genetika MeSH
- myši inbrední C3H MeSH
- myši transgenní MeSH
- myši MeSH
- ovarium enzymologie MeSH
- regulace genové exprese MeSH
- sekvence aminokyselin MeSH
- testis enzymologie MeSH
- umělé bakteriální chromozomy MeSH
- vznik druhů (genetika) MeSH
- zvířata MeSH
- Check Tag
- mužské pohlaví MeSH
- myši MeSH
- ženské pohlaví MeSH
- zvířata MeSH
BACKGROUND: Prostate specific membrane antigen (PSMA), also called glutamate carboxypeptidase II (GCPII), is a target enzyme for diagnosis and treatment of prostate cancer. Moreover, it is upregulated in the vasculature of most solid tumors and is therefore a potential target for the generation of novel antineoplastics. In this context, we analyze the possibility of using rat and pig as animal models for enzymologic and in vivo studies. METHODS: We prepared the recombinant extracellular part of human, rat, and pig GCPII in S2 cell media and characterized the activity and inhibition profiles of the three orthologs by radioenzymatic assay. We performed Western blot analysis of GCPII expression in human, rat, and pig tissues using the monoclonal antibody GCP-04 and confirmed these findings by activity measurements and immunohistochemistry. RESULTS: The three recombinant proteins show similar specific enzymatic activities and inhibition profiles. Tissue expression analysis revealed that most of the pig and human tissues show at least some GCPII-positivity, while the expression pattern in rat is more restricted. Moreover, tissues such as prostate and testes exhibit different GCPII expression levels among the species studied. CONCLUSIONS: The rat and pig orthologs of GCPII seem to be suitable to approximate human GCPII in enzymologic studies. However, the diffuse expression pattern of GCPII in animal and human tissues could be a caveat for the potential utilization of GCPII-targeted anticancer drugs. Furthermore, variations in GCPII tissue distribution among the species studied should be considered when using rat or pig as models for antineoplastic drug discovery.
- MeSH
- druhová specificita MeSH
- financování organizované MeSH
- krysa rodu rattus MeSH
- ledviny enzymologie patologie MeSH
- lidé MeSH
- mícha enzymologie patologie MeSH
- miniaturní prasata MeSH
- modely u zvířat MeSH
- molekulární sekvence - údaje MeSH
- potkani inbrední LEW MeSH
- prasata MeSH
- prostata enzymologie patologie MeSH
- prostatický specifický antigen analýza genetika metabolismus MeSH
- regulace genové exprese enzymů MeSH
- sekvence aminokyselin MeSH
- testis enzymologie patologie MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- lidé MeSH
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- srovnávací studie MeSH
- MeSH
- 11-beta-hydroxysteroiddehydrogenasa typ 2 fyziologie metabolismus škodlivé účinky MeSH
- Cushingův syndrom enzymologie etiologie MeSH
- finanční podpora výzkumu jako téma MeSH
- financování organizované MeSH
- hormony kůry nadledvin imunologie metabolismus MeSH
- kortison fyziologie metabolismus škodlivé účinky MeSH
- ledviny enzymologie metabolismus MeSH
- lidé MeSH
- mozek enzymologie fyziologie metabolismus MeSH
- renální hypertenze enzymologie metabolismus patofyziologie MeSH
- testis enzymologie fyziologie metabolismus MeSH
- Check Tag
- lidé MeSH
- MeSH
- antihypertenziva MeSH
- diuretika farmakologie MeSH
- hydroxysteroiddehydrogenasy antagonisté a inhibitory MeSH
- inhibitory enzymů farmakologie MeSH
- krysa rodu rattus MeSH
- ledviny enzymologie ultrastruktura MeSH
- testis enzymologie MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- srovnávací studie MeSH