Tetracycline and doxycycline are commonly used antibiotics in acne treatment during puberty in humans. The long-term effect of these antibiotics on male reproductive tract development has not been fully elucidated. For this reason we tested the effect of antibiotics on the reproductive parameters of mice males during puberty with the therapeutic dose used in humans, and with lower and higher doses. The outbred mouse strain CD1 with higher heterozygosity was exposed for 14 days at puberty. Adult males at the age of 70 days were used for the measurements. We observed a significant decrease in anogenital distance and thickness of the seminiferous epithelium in the treated animals. Pathological changes in the testes had an impact on sperm quality; a higher number of sperm positively stained with Annexin V and TUNEL and a lower number of acrosome-intact sperm was detected. In conclusion, the treatment of male mice with antibiotics in puberty led to long-lasting effects on reproductive organs and spermatozoa in adult males.
- Klíčová slova
- Apoptosis, Doxycycline, Puberty, Sperm, Testes, Tetracycline,
- MeSH
- antibakteriální látky aplikace a dávkování škodlivé účinky MeSH
- apoptóza účinky léků MeSH
- doxycyklin aplikace a dávkování škodlivé účinky MeSH
- myši MeSH
- outbrední kmeny zvířat MeSH
- průtoková cytometrie MeSH
- spermie účinky léků patologie MeSH
- stárnutí účinky léků patologie MeSH
- tělesná hmotnost účinky léků MeSH
- testis účinky léků růst a vývoj patologie MeSH
- tetracyklin aplikace a dávkování škodlivé účinky MeSH
- velikost orgánu účinky léků MeSH
- vztah mezi dávkou a účinkem léčiva MeSH
- zvířata MeSH
- Check Tag
- mužské pohlaví MeSH
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- antibakteriální látky MeSH
- doxycyklin MeSH
- tetracyklin MeSH
The increased fetoplacental vascular resistance due to chronic hypoxia cannot be explained by simple hypoxic vasoconstriction, as it sustains to some degree after recovery in normobaric environment. To verify a hypothesis that fetoplacental arteries undergo remodeling of their walls similar to remodeling of pulmonary arteries in hypoxic pulmonary hypertension, we used a model of the chronically hypoxic rat placenta. Han Wistar pregnant rats were exposed to 14-day hypoxia (10% of oxygen) during the 6th to 19th day of pregnancy. Chronic hypoxia elicited in both intraplacental (prelabyrinthine) and chorionic plate (insertion) arteries significant narrowing of their lumina. Irregular thickening of their adventitia due to an increase in collagen fibers as well as ground substance was observed; reticular fibers were fragmented. Because of remodeling of fetoplacental arteries, a model of chronically hypoxic rat placenta could simulate human preplacental hypoxia and consequent effects.
- MeSH
- arteriae umbilicales patofyziologie ultrastruktura MeSH
- cévní rezistence MeSH
- chorion * krevní zásobení ultrastruktura MeSH
- hypoxie patologie patofyziologie MeSH
- inbrední kmeny potkanů MeSH
- komplikace těhotenství patologie patofyziologie MeSH
- krysa rodu Rattus MeSH
- placenta * krevní zásobení ultrastruktura MeSH
- placentární oběh fyziologie MeSH
- těhotenství MeSH
- transmisní elektronová mikroskopie MeSH
- vazokonstrikce MeSH
- zvířata MeSH
- Check Tag
- krysa rodu Rattus MeSH
- mužské pohlaví MeSH
- těhotenství MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Unexpected, sometimes opposite effects of dietary isoflavonic phytoestrogens on immunity may suggest that classical mammalian toxicological assays are not entirely suitable for preclinical safety tests of these compounds. We evaluated a new alternative model of haemocytes of Egyptian cotton worm in vivo following genistein administration. Genistein induced significant changes in nucleolar morphology of haemocytes but did not influence their counts and nucleolar indices. The results indicate that genistein does not affect proliferation and differentiation of normal cells but potentiates their immuno-competence. Egyptian cotton worm larvae seem to be the new alternative biomodel for immunological screening.
- MeSH
- biologické modely MeSH
- buněčná diferenciace účinky léků MeSH
- buněčná imunita účinky léků MeSH
- buněčné jadérko účinky léků MeSH
- fytoestrogeny farmakologie MeSH
- genistein farmakologie MeSH
- hemocyty cytologie účinky léků imunologie MeSH
- proliferace buněk účinky léků MeSH
- Spodoptera MeSH
- toxikologie metody MeSH
- zvířata MeSH
- Check Tag
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- fytoestrogeny MeSH
- genistein MeSH
This study was carried out to investigate the role of lead in the development of oxidative stress in the brain. We examined the rate of lipid peroxidation and we determined lipid fluorescence products (lipofuscin-like pigments - LFP) as a marker of lipid peroxidation after short in vitro incubation of rat brain homogenates with lead acetate (10(-2), 10(-4), 10(-6) M lead acetate, 2 h). Simultaneously we examined by the same method in vivo indices of oxidative stress in brains of mice exposed for 12 weeks to 0.2% lead acetate in drinking water. The results show that the concentration of LFP in rat brain homogenates increased significantly after 2 h incubation with 10(-2) M lead acetate as compared to controls (P<0.0001). This effect was not observed in lower doses of lead acetate (10(-4) and 10(-6) M). After the long-term exposure of mice to 0.2% lead acetate, pronounced accumulation of lead and significantly increased concentration of LFP (P<0.004) in the brains of exposed animals as compared to controls were observed. The evidence for the formation of specific fluorophores originating from oxidative damage was shown also in qualitative changes in 3D spectral arrays and synchronous spectra. The presented results proved the influence of lead on the activation of radical reactions in the brain after short in vitro exposure of rat brain as well as within long-term in vivo exposure in mice using lipofuscin-like pigments as an indicator of oxidative stress.
- MeSH
- aplikace orální MeSH
- biologické markery metabolismus MeSH
- časové faktory MeSH
- fluorescenční spektrometrie MeSH
- inbrední kmeny myší MeSH
- krysa rodu Rattus MeSH
- lipofuscin metabolismus MeSH
- mozek účinky léků metabolismus MeSH
- myši MeSH
- olovo farmakokinetika toxicita MeSH
- oxidační stres účinky léků MeSH
- peroxidace lipidů účinky léků MeSH
- pitná voda MeSH
- potkani Wistar MeSH
- techniky in vitro MeSH
- volné radikály metabolismus MeSH
- zvířata MeSH
- Check Tag
- krysa rodu Rattus MeSH
- mužské pohlaví MeSH
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- biologické markery MeSH
- lipofuscin MeSH
- olovo MeSH
- pitná voda MeSH
- volné radikály MeSH
The objective of this study was to investigate the morphological effects of postnatal exposure to benzo[a]pyrene (B[a]P) on the development of the uterus, uterine estrogen receptor (ERalpha) expression, and the uterine response to estrogen stimulation using the uterotrophic bioassay in rats. Neonates were injected on each postnatal day (PND) 1-14 with B[a]P (0.1, 1.0 and 10.0mg/kg), ethynylestradiol (EE; 1.0 microg/kg) or vehicle (control group). All animals were killed on PND 23. Postnatal administration of B[a]P with doses of 1.0 and 10.0 mg/kg induced significant (P<0.01) reduction of uterine weight and significantly lowered (P<0.05) ERalpha expression in the luminal epithelium. The increase in uterine weight and luminal epithelium heights after EE stimulation (1.0 microg/kg) on PND 20-22 was significantly higher (P<0.01) in all groups in comparison with corresponding non-stimulated groups. However, the uterotrophic response in rats postnatally exposed to EE and B[a]P was significantly lower (P<0.01) than in controls. In the control and EE groups, EE stimulation on PND 20-22 induced a significant (P<0.01) decrease in ERalpha immunoreactivity of the luminal epithelium. In contrast, rats postnatally treated with B[a]P showed no change in the density of ERalpha immunostaining when detected after estrogenic stimulation. The present study showed that postnatal exposure to B[a]P caused pathological changes in constitution and maturation of uterine ERalpha resulting in disturbed morphological development and uterine dysfunction in immature rats.
- MeSH
- alfa receptor estrogenů účinky léků metabolismus MeSH
- antagonisté estrogenu toxicita MeSH
- benzopyren toxicita MeSH
- buněčné jádro účinky léků metabolismus patologie MeSH
- epitelové buňky účinky léků patologie MeSH
- estrogeny farmakologie MeSH
- ethinylestradiol farmakologie MeSH
- fluorescenční protilátková technika přímá MeSH
- imunoenzymatické techniky MeSH
- injekce subkutánní MeSH
- kombinovaná farmakoterapie MeSH
- krysa rodu Rattus MeSH
- novorozená zvířata MeSH
- pohlavní dospělost MeSH
- potkani Wistar MeSH
- uterus účinky léků růst a vývoj patologie MeSH
- velikost orgánu účinky léků MeSH
- vztah mezi dávkou a účinkem léčiva MeSH
- zvířata MeSH
- Check Tag
- krysa rodu Rattus MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- alfa receptor estrogenů MeSH
- antagonisté estrogenu MeSH
- benzopyren MeSH
- estrogeny MeSH
- ethinylestradiol MeSH
Hepatic stellate cells (HSC) and liver myofibroblasts (MFB) are two cell populations most likely responsible for the synthesis of most connective tissue components in fibrotic liver. They differ in their origin and location, and possibly in patterns of gene expression. Normal and carbon tetrachloride-cirrhotic livers from rats were used to isolate HSC. Liver was perfused with pronase and collagenase solutions, followed by centrifugation of the cell suspension on a density gradient. HSC were quiescent 2 days after plating on plastic but they became activated after another 5 days in culture. When the culture was passaged 5 times, its character changed profoundly as HSC were replaced by MFB. Microarray analysis was used to determine gene expression in quiescent HSC, activated HSC and MFB. The expression of 49 genes coding for connective tissue proteins, proteoglycans, metalloproteinases and their inhibitors, growth factors and cellular markers was determined. The pattern of gene expression changed during HSC activation and there were distinct differences between HSC and MFB. Little difference between normal cells and cells isolated from cirrhotic liver was found.
- MeSH
- chlorid uhličitý toxicita MeSH
- experimentální cirhóza jater metabolismus MeSH
- exprese genu MeSH
- extracelulární matrix chemie MeSH
- fibroblasty cytologie účinky léků metabolismus MeSH
- imunohistochemie MeSH
- játra cytologie účinky léků metabolismus MeSH
- krysa rodu Rattus MeSH
- kultivované buňky MeSH
- messenger RNA biosyntéza účinky léků MeSH
- metaloproteasy genetika metabolismus MeSH
- myocyty hladké svaloviny cytologie účinky léků metabolismus MeSH
- pojivová tkáň účinky léků metabolismus MeSH
- polymerázová řetězová reakce s reverzní transkripcí MeSH
- proteoglykany genetika metabolismus MeSH
- sekvenční analýza hybridizací s uspořádaným souborem oligonukleotidů MeSH
- tkáňové inhibitory metaloproteinas genetika metabolismus MeSH
- zvířata MeSH
- Check Tag
- krysa rodu Rattus MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- srovnávací studie MeSH
- Názvy látek
- chlorid uhličitý MeSH
- messenger RNA MeSH
- metaloproteasy MeSH
- proteoglykany MeSH
- tkáňové inhibitory metaloproteinas MeSH
We studied the dose response of pulmonary changes at 3 weeks after 1-25 Gy irradiation and we investigated the effects of an anti-inflammatory drug. Wistar rats were given a single dose of 1-25Gy irradiation to the thorax. Group one was treated with saline only, while group two was administered subcutaneously a combination of pentoxifylline (35 mg/kg) and dexamethasone (1 mg/kg) twice per week. Lungs were examined histochemically and number of neutrophile granulocytes, alveolar septal thickness, air/tissue ratio, number of alveoli per field, number of type II pneumocytes per alveolus, and occludin 1 expression were measured. A significant dose-dependent depletion of type II pneumocytes was found after irradiation with a dose of 1 Gy and higher. Alveolar neutrophils increased after 1 Gy with a dose dependency noted after 10-25Gy and alveolar septa thickening followed 5-25 Gy. A lower occludin 1 expression was observed in animals irradiated with the doses of 5 20 Gy, indicating an effect on vascular permeability. Anti-inflammatory therapy partially inhibited the increase of neutrophils at all radiation doses and the depletion of type II pneumocytes after doses of 1, 10, and 15 Gy. Occludin 1 did not decrease in the lungs of rats treated with the anti-inflammatory drugs as it did in most rats treated only with saline. Our results suggest that pneumocytes depletion is a major factor responsible for radiation pneumonitis development and that these changes may be compensated for provided radiation doses are below the threshold.
- MeSH
- antiflogistika terapeutické užití MeSH
- dexamethason terapeutické užití MeSH
- imunoenzymatické techniky MeSH
- kapilární permeabilita účinky záření MeSH
- kombinovaná farmakoterapie MeSH
- krysa rodu Rattus MeSH
- membránové proteiny metabolismus MeSH
- modely nemocí na zvířatech MeSH
- neutrofily patologie účinky záření MeSH
- okludin MeSH
- pentoxifylin terapeutické užití MeSH
- plicní alveoly metabolismus patologie účinky záření MeSH
- potkani Wistar MeSH
- radiační pneumonitida farmakoterapie patologie MeSH
- radioprotektivní látky terapeutické užití MeSH
- techniky in vitro MeSH
- vztah dávky záření a odpovědi MeSH
- zvířata MeSH
- Check Tag
- krysa rodu Rattus MeSH
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- antiflogistika MeSH
- dexamethason MeSH
- membránové proteiny MeSH
- Ocln protein, rat MeSH Prohlížeč
- okludin MeSH
- pentoxifylin MeSH
- radioprotektivní látky MeSH
Histological examination of 38 nodular formations extirpated from the site of vaccine administration to cats disclosed 25 cases of sarcoma and 13 of granuloma. Average age of the cats bearing sarcoma was 8.75 years whereas granuloma occurred at average age of 1.9 year. This age-relationship of the lesions, as well as their similar morphologic features indicated a progression of chronic inflammatory changes to tumors. Similar tumors were diagnosed in one cat with "posttraumatic ocular sarcoma" and in the uterus of female-cat with long-standing pyometra. These two cats were 15 and 8 years old, respectively. Experimental study of local reaction 21 days after administration of commercial, lipid-adjuvanted vaccine revealed in young cats (age 9 months) a reaction to immunogen, whereas in old animals (age 10 to 15 years) there was a reaction to foreign material. The data suggest that chronic inflammation and age-related immunodeficiency are instrumental in pathogenesis of the vaccine-associated sarcoma.
- MeSH
- alkalická fosfatasa analýza MeSH
- hostitel s imunodeficiencí MeSH
- imunoenzymatické techniky veterinární MeSH
- karboxylesterasa analýza MeSH
- kočky MeSH
- kyselá fosfatasa analýza MeSH
- nádory měkkých tkání enzymologie etiologie patologie veterinární MeSH
- nemoci koček patologie MeSH
- sarkom enzymologie etiologie patologie veterinární MeSH
- vakcinace škodlivé účinky veterinární MeSH
- zánět komplikace enzymologie patologie veterinární MeSH
- zvířata MeSH
- Check Tag
- kočky MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- alkalická fosfatasa MeSH
- karboxylesterasa MeSH
- kyselá fosfatasa MeSH
The aim of this study was to evaluate the effect of chronic uremia induced by 5/6 nephrectomy (5/6NX) on changes in protein and branched-chain amino acid (BCAA; valine, leucine and isoleucine) metabolism. The control group consisted of sham operated rats. Twenty eight weeks after surgery the parameters of protein and amino acid metabolism were evaluated using a primed constant intravenous infusion of L-[1-(14)C]leucine. A drop in BCAA levels and a significant increase in urea, creatinine and cholesterol were observed in plasma of all 5/6NX rats. However, severe uremia with acidosis developed only in one third of rats with 5/6NX. In 5/6NX rats with acidosis significant increases in proteolysis, leucine oxidation, leucine oxidized fraction, and leucine clearance were observed in comparison with the control group and rats with 5/6NX without acidosis. In addition, in 5/6NX rats with acidosis a significant decrease in valine concentration in gastrocnemius muscle was found. We conclude that marked activation of proteolysis occurs in severe chronic renal failure and is probably caused by metabolic changes related to acidosis development.
- MeSH
- acidóza etiologie metabolismus MeSH
- cholesterol krev MeSH
- chronické selhání ledvin metabolismus patologie MeSH
- isoleucin metabolismus MeSH
- kosterní svaly metabolismus MeSH
- kreatinin krev MeSH
- krysa rodu Rattus MeSH
- leucin metabolismus MeSH
- močovina krev MeSH
- modely nemocí na zvířatech MeSH
- nefrektomie MeSH
- potkani Wistar MeSH
- přijímání potravy fyziologie MeSH
- proteiny metabolismus MeSH
- tělesná hmotnost fyziologie MeSH
- uremie etiologie metabolismus MeSH
- valin metabolismus MeSH
- zvířata MeSH
- Check Tag
- krysa rodu Rattus MeSH
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- cholesterol MeSH
- isoleucin MeSH
- kreatinin MeSH
- leucin MeSH
- močovina MeSH
- proteiny MeSH
- valin MeSH
Highly reactive oxygen-free radicals are implicated in the pathogenic process of various diseases. Using an animal model of diabetes (alloxan-induced hyperglycaemia in mice), a model of gastric ulcer (indomethacin-induced gastric lesion in rats), and a model of bronchial asthma (ovalbumin-induced allergic bronchospasm in guinea pigs), a potential therapeutic effect was tested in known antioxidant drugs (alpha-tocopherol, ubiquinone), the thio-compound mesna, and drugs with a possible antioxidant effect (substances derived from the ergoline structure: 6-hydroxynicotinic acid and 4-hydroxypyridine). The pre-treatment with ubiquinone and 6-hydroxynicotinic acid almost completely prevented alloxan-induced hyperglycaemia (94 and 93% inhibition of hyperglycaemia, respectively). A weaker effect was shown by alpha-tocopherol and 4-hydroxypyridine (31 and 27% inhibition of hyperglycaemia, respectively). Mesna negligibly increased hyperglycaemia. 32% and 21% inhibitions of the number of gastric lesions were shown after administration of 6-hydroxynicotinic acid and alpha-tocopherol, respectively. Other drugs, most markedly mesna, aggravated gastric lesions. The most marked protective effect on ovalbumin-induced bronchospasm was exerted by 6-hydroxynicotinic acid (the pulmonary ventilation was increased by 84% in comparison with control group), while mesna and (alpha-tocopherol had a weaker effect (amelioration by 50 and 51 %, respectively). Ubiquinone and 4-hydroxypyridine aggravated pulmonary ventilation. The most marked protective effect in the animal models used was shown by 6-hydroxynicotinic acid.
- MeSH
- alloxan MeSH
- antioxidancia farmakologie MeSH
- bronchospasmus prevence a kontrola MeSH
- experimentální diabetes mellitus prevence a kontrola MeSH
- hydroxylový radikál MeSH
- indomethacin toxicita MeSH
- krysa rodu Rattus MeSH
- modely nemocí na zvířatech MeSH
- morčata MeSH
- myši MeSH
- potkani Wistar MeSH
- žaludeční sliznice účinky léků patologie MeSH
- zvířata MeSH
- Check Tag
- krysa rodu Rattus MeSH
- morčata MeSH
- mužské pohlaví MeSH
- myši MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- alloxan MeSH
- antioxidancia MeSH
- hydroxylový radikál MeSH
- indomethacin MeSH