RESUMO
The pharmacological activity of granulocyte CSF (G-CSF) immobilized using electron-beam synthesis nanotechnology (imG-CSF) was evaluated in an experimental model of ovarian reserve depletion. The effectiveness of the drug was compared with that of its unmodified form. Depletion of the ovarian follicular pool in female Sprague-Dawley rats was caused by a single intravenous injection of the antitumor drug etoposide in the maximum tolerated dose. The effectiveness of the studied drugs was assessed by serum concentration of anti-Mullerian hormone (AMH) measured by ELISA and by the number of primordial, two-layer, multilayer, and atretic follicles counted on serial sections of the ovaries (5-µm thick; through the entire organ) stained with hematoxylin and eosin. It was found that imG-CSF prevents depletion of the ovarian reserve in the model used, which was confirmed by high AMH concentration and higher numbers of primordial, two- and multilayer follicles in comparison with the corresponding parameters in the control (etoposide), and by a decrease in the severity of atretic processes. Unmodified form of the drug demonstrated lower efficiency.
Assuntos
Reserva Ovariana , Ratos , Animais , Feminino , Etoposídeo , Fator Estimulador de Colônias de Granulócitos/farmacologia , Elétrons , Ratos Sprague-Dawley , Hormônio Antimülleriano , Modelos TeóricosRESUMO
We studied ante- and postnatal development of the offspring of intact female rats crossed with males injected with low doses of methotrexate 3 and 6 months before mating. The time of crossing corresponded to the manifestation of the cytostatic effect on spermatogonial stem cells. The offspring of methotrexate-treated males was characterized by increased preimplantation losses and fetal growth restriction in the antenatal period and inhibition of physical development, delayed formation of sensory-motor reflexes, and impaired learning abilities in the postnatal period.
Assuntos
Metotrexato , Efeitos Tardios da Exposição Pré-Natal , Humanos , Ratos , Animais , Gravidez , Feminino , Masculino , Metotrexato/farmacologia , Efeitos Tardios da Exposição Pré-Natal/induzido quimicamente , Reprodução , Aprendizagem , ReflexoRESUMO
We studied the effect of antioxidants dibornol (2,6-diisobornyl-4-methylphenol) and its derivative (4-hydroxymethyl-2,6-diisobornylphenol), members of the alkylated phenols group, on the redox potential of male germ cells and their morphological and functional state in the rat model of pathospermia. Pharmacological effect was observed in animals treated with dibornol. The studied compounds led to the normalization of the antioxidant-prooxidant balance. However, the value of this indicator against the background of treatment with dibornol derivative attested to a shift in the redox balance of cells towards reduction reactions.
Assuntos
Antioxidantes , Fenóis , Masculino , Animais , Ratos , Antioxidantes/farmacologia , Antioxidantes/uso terapêutico , Antioxidantes/metabolismo , Espécies Reativas de Oxigênio , Oxirredução , Fenóis/farmacologia , Fenóis/uso terapêutico , Células Germinativas/metabolismoRESUMO
Delayed gonadotoxic effects were revealed in outbred male sexually mature rats (SD) after exposure to paclitaxel in the prepubertal period, and the possibility of their correction with p-tyrosol was shown. It was found, that administration of paclitaxel does not inhibit the ability of animals to conceive, but impairs the reserve capacity of the testicular tissue. In intact female rats crossed with male rats receiving paclitaxel, increased post-implantation fetal death was observed. Combined administration of paclitaxel and p-tyrosol alleviated the delayed effects of the cytostatic treatment on the prepubertal testis.
Assuntos
Álcool Feniletílico , Testículo , Animais , Feminino , Masculino , Paclitaxel/toxicidade , Álcool Feniletílico/análogos & derivados , Álcool Feniletílico/farmacologia , RatosRESUMO
The regenerative properties of p-tyrosol were investigated in a model of testicular insufficiency caused by a toxic effect on spermatogonial stem cells (single administration of paclitaxel in the maximum tolerable dose). Against the background of p-tyrosol administration, we observed an increase in the number of normal spermatogonia and Sertoli cells, stimulation of spermatogenesis, and renewal of the spermatogenic tissue. The treatment with p-tyrosol also led to a decrease in DNA damage in cells of the testicular tissue. These changes were accompanied by a decrease in the level of free radicals, an increase in antioxidant protection, and normalization of the redox potential.
Assuntos
Espermatogônias , Testículo , Humanos , Masculino , Álcool Feniletílico/análogos & derivados , Espermatogênese , Células-TroncoRESUMO
The morphological and functional state of the reproductive system was studied in male outbred rats (SD stock) and male F1(CBA×C57BL/6) mice after long-term (3 months) methotrexate administration. The drug was administered subcutaneously once a week for 4 weeks, the dose for male rats was 1 mg/kg, for male mice 2.2 mg/kg. It was found that male rats retained the ability to conceive, their reproductive potential was not limited by increased risk of embryo death. At the same time, signs of astheno- and pathospermia were revealed. The testicular tissue was characterized by reduced content of the sources of the proliferative pool of spermatogenesis. In mice treated with methotrexate, increased content of DNA breaks was detected in the testicular cells.
Assuntos
Metotrexato , Espermatogênese , Animais , Masculino , Metotrexato/toxicidade , Camundongos , Ratos , Reprodução , TestículoRESUMO
We studied possible toxic effects of antiviral drug Kagocel on reproductive function in pubertal male rats. The drug was administered in therapeutic and 10-fold higher doses throughout the spermatogenesis cycle (48 days). Kagocel did not reduce mating and fertilizing capacities, did not suppress spermatogenesis, and had no toxic effects on the offspring. The results characterize Kagocel as a drug with a broad reproductive safety profile and demonstrate that the age limits for using Kagocel in pediatric practice can be extended.
Assuntos
Antivirais/efeitos adversos , Gossipol/efeitos adversos , Espermatogênese/efeitos dos fármacos , Animais , Masculino , Puberdade/efeitos dos fármacos , Ratos , Ratos Sprague-Dawley , Comportamento Sexual Animal/efeitos dos fármacos , Testículo/efeitos dos fármacosRESUMO
Effectiveness of the granulocyte colony-stimulating factor immobilized by using electronbeam synthesis nanotechnology was investigated on the model of experimental testicular failure caused by the toxic effect on stem spermatogonia. Administration of the drug to experimental paclitaxel-treated animals increased the number of sources of the proliferative pool of spermatogenesis and its productivity. The effectiveness of immobilized granulocyte colony-stimulating factor was based on its ability to stimulate reparative regeneration of the spermatogenic tissue, which manifested in a decrease in spermatogenic layer maturity and increase in the number of microenvironment cells. Effectiveness of the immobilized form of the drug was superior to that of non-immobilized form.
Assuntos
Fator Estimulador de Colônias de Granulócitos/farmacologia , Proteínas Imobilizadas/farmacologia , Infertilidade Masculina/tratamento farmacológico , Espermatogônias/fisiologia , Animais , Antineoplásicos/efeitos adversos , Avaliação Pré-Clínica de Medicamentos , Fator Estimulador de Colônias de Granulócitos/uso terapêutico , Proteínas Imobilizadas/uso terapêutico , Infertilidade Masculina/induzido quimicamente , Masculino , Nanotecnologia , Paclitaxel/efeitos adversos , Ratos Wistar , Regeneração , Espermatogênese , Espermatogônias/efeitos dos fármacosRESUMO
A course of dihydroquercetin (antioxidant) injections to 5-month-old Wistar rats with sulpiride-induced benign prostatic hyperplasia led to reduction of proliferative activity in the glandular structures and to attenuation of the inflammatory reaction in the tissue. Prostatic antioxidant/prooxidant balance returned to normal after the treatment.
Assuntos
Antioxidantes/metabolismo , Hiperplasia Prostática/induzido quimicamente , Hiperplasia Prostática/tratamento farmacológico , Hiperplasia Prostática/patologia , Quercetina/análogos & derivados , Espécies Reativas de Oxigênio/metabolismo , Sulpirida/efeitos adversos , Animais , Técnicas Histológicas , Masculino , Quercetina/administração & dosagem , Quercetina/metabolismo , Quercetina/farmacologia , Ratos , Ratos Wistar , Estatísticas não ParamétricasRESUMO
Comparative evaluation of the efficiency of prostatotropic agents was carried out in rat experiments. Serenoa repens plant preparation and polypeptides isolated from the cattle prostate were used for the treatment of benign hyperplasia. Drugs in parallel with sulpiride similarly led to shrinkage of the acinar epithelial area and to emergence of a trend to an increase of the stromal/epithelial proportion, more so after Serenoa repens treatment.
Assuntos
Peptídeos/uso terapêutico , Fitoterapia , Extratos Vegetais/uso terapêutico , Hiperplasia Prostática/tratamento farmacológico , Animais , Bovinos , Masculino , Próstata , Hiperplasia Prostática/induzido quimicamente , Ratos , Serenoa , SulpiridaRESUMO
The possibility of reducing the ovariotoxicity of antitumor drug etoposide with buserelin, a hypothalamic regulator of pituitary function, was studied in female Wistar rats. Quantitative analysis of ovarian structural and functional elements on serial sections through the entire organ showed that 3 months after combined treatment with etoposide and buserelin, the morphological picture of the ovarian glands did not differ from that in intact animals of the same age, while etoposide monotherapy led to earlier development of atrophic processes. Six months after treatment, the number of bi- and multilayer follicles was significantly higher in rats receiving combined therapy compared to animals treated with etoposide alone.
Assuntos
Antineoplásicos Fitogênicos/toxicidade , Busserrelina/farmacologia , Etoposídeo/toxicidade , Fármacos para a Fertilidade Feminina/farmacologia , Ovário/efeitos dos fármacos , Animais , Feminino , Ratos , Ratos WistarRESUMO
Progeny of Wistar rats treated with vepesid 1, 3, and 6 months before mating is characterized by common pathological changes. These changes were more pronounced and more diverse in animals descending from females receiving the cytostatic compared to the progeny of treated males. The severity of toxic effects depended on the period between mating and vepesid treatment. Cytostatic treatment 3 months before mating was associated with minimum toxicity for the progeny.
Assuntos
Anormalidades Induzidas por Medicamentos , Antineoplásicos Fitogênicos/toxicidade , Etoposídeo/toxicidade , Efeitos Tardios da Exposição Pré-Natal , Animais , Animais Recém-Nascidos , Feminino , Morte Fetal/induzido quimicamente , Masculino , Gravidez , Ratos , Ratos Wistar , Fatores de Tempo , Inibidores da Topoisomerase IIRESUMO
Experiments on adult rats showed that a single intravenous injection of antitumor drug vepeside in a MTD (maximum tolerable dose) reduced the reproductive status during periods corresponding to exposure of mature sex cells, spermatocytes, and spermatogonia in male rats and exposure of oocytes in ovulating, mature, and primordial follicles in female rats. Reduction of the male and female reproductive function manifested in increased antenatal mortality of the progeny. The toxic effects of the drug on mature male sex cells caused temporary partial infertility.