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1.
J Biochem Mol Toxicol ; 36(8): e23085, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-35499814

RESUMO

Propafenone is a well-known Class 1C antiarrhythmic agent that has sodium channel blocking properties as well as the ability to block 13 other channels and a modest calcium antagonistic effect. Propafenone has a profound electrophysiologic effect on auxiliary atrioventricular circuits and in patients with atrioventricular nodal reentry tachycardia can obstruct conduction in the fast conducting pathway. Furthermore, propafenone is less likely than other Class 1C drugs to cause proarrhythmia. However, although this medicine can pass through the placenta, the effects during pregnancy remain unknown. Here, we investigated the potential teratogenic and genotoxic effects of Rythmol during rat development. Pregnant Wistar rats received 46.25 mg/kg body weight of propafenone daily by gavage from Gestation Day (GD) 5 to GD 19. At GD 20, the dams were dissected, and their fetuses were assessed via morphologic, skeletal, and histologic investigation. In addition, a comet assay was used to measure DNA impairment of fetal skull osteocytes and hepatic cells. The study showed that propafenone treatment of pregnant rats led to a marked decrease in gravid uterine weight, number of implants/litter, number of viable fetuses, and bodyweight of fetuses but a clear increase in placental weight and placental index in the treated group. Frequent morphologic abnormalities and severe ossification deficiency in the cranium bones were observed in the treatment group. Various histopathological changes were observed in the liver, kidney, and brain tissues of maternally treated fetuses. Similarly, propafenone induced DNA damage to examined samples. Thus, our study indicates that propafenone may be embryotoxic in humans.


Assuntos
Placenta , Propafenona , Animais , Antiarrítmicos/farmacologia , Antiarrítmicos/uso terapêutico , Feminino , Humanos , Gravidez , Propafenona/farmacologia , Propafenona/uso terapêutico , Ratos , Ratos Wistar , Teratogênicos
2.
Andrologia ; 54(4): e14362, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-34970779

RESUMO

In the current study, we synthesized and prepared a curcumin and vitamin E nanocomposite coated with olive oil (CEONC). Curcumin, vitamin E, and olive oil are fundamental organic antioxidants, and forming nanoparticles from these components endows them with special characteristics. We investigated the protective effect of CEONC on reproductive toxicity induced by cadmium chloride (CdCl2 ) in male rats. Forty rats (170-180 g) were randomly assigned to four groups: Group 1 (control) received oral distilled water; Group 2 intraperitoneal injection with CEONC (30 mg/kg); Group 3 received oral CdCl2 (5 mg/kg); and Group 4 received CdCl2 (5 mg/kg) followed by CEONC (30 mg/kg) for 4 weeks. After 50 days, we terminated the experiment and assessed male reproductive hormones, sperm motility, viability and morphology, and testes histopathology and conducted a comet assay. The results revealed that co-administration of CEONC with CdCl2 exposure increased reproductive hormone levels, improved sperm motility and viability, prevented sperm morphological changes, recovered the testicular histology, and decreased DNA damage in the testicular tissue compared to rats exposed to CdCl2 alone. CEONC administration produced no adverse effects and enhanced all sperm parameters. Our findings demonstrate that CEONC is a potential treatment for preventing reproductive damage induced by cadmium exposure.


Assuntos
Curcumina , Nanocompostos , Animais , Cloreto de Cádmio/toxicidade , Curcumina/farmacologia , Curcumina/uso terapêutico , Masculino , Azeite de Oliva/farmacologia , Estresse Oxidativo , Ratos , Motilidade dos Espermatozoides , Testículo , Vitamina E/farmacologia , Vitamina E/uso terapêutico
3.
J Biochem Mol Toxicol ; 35(1): e22613, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33016600

RESUMO

This experiment was performed to evaluate the possible embryotoxic and teratogenic effects of doxycycline during rat development. Twenty-one female rats were used and distributed into three groups equally (seven animals/group). The low dose group received doxycycline at a dose of 5 mg/kg bw/day orally from the 6th to 14th day of gestation. The high dose group received 10 mg/kg bw/day orally for the same period, the Control group received 1 mL distilled water orally for the same period. The dams were dissected on the 20th day of gestation and their fetuses were subjected to morphological, skeletal, and histological examination. Moreover, DNA damage analysis of liver cells of pregnant rats and their fetuses or fetal skull was assessed by Comet assay. The obtained results showed a significant decrease in fetal body weight, several morphological anomalies, and severe lack of ossification on the skull bones, phalanges, and sternum bone as well as shortness in the ulna and radius bones. Histological studies of pregnant rats revealed congestion and dilatation of the central vein of the liver lobules and fatty degeneration of the hepatocytes. In addition, 20 day-fetuses showed a marked increase of necrotic hepatocytes associated with an increased average of megakaryocytes and periportal leukocytic infiltration. Moreover, doxycycline induced a significant increase in the percentage of DNA damage and tail length of examined samples. Conclusively, doxycycline caused certain fetal abnormalities, so it is advisable to avoid using this drug during pregnancy.


Assuntos
Doxiciclina/efeitos adversos , Doxiciclina/farmacologia , Embrião de Mamíferos/embriologia , Desenvolvimento Embrionário/efeitos dos fármacos , Feto/embriologia , Organogênese/efeitos dos fármacos , Animais , Feminino , Feto/patologia , Gravidez , Ratos , Ratos Wistar
4.
Reprod Biol ; 23(1): 100724, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36563520

RESUMO

Fluoride is a common environmental contaminant that has harmful effects on human health when it is present in high concentrations. Fluoride enters the bloodstream after being absorbed by the gastrointestinal system when fluoride-contaminated groundwater is consumed by people. The aim of the present study was to determine whether polyphenol-rich nano Moringa oleifera (NMO) could protect rat testicles from sodium fluoride (NaF) damage by evaluating sperm quality, sex hormones, testicular oxidative status, histopathology, and StAR gene expression. Twenty-eight adult Wistar rats were divided equally and randomly into four groups: group one received distilled water; group two received NMO at a dosage of 250 mg/kg/body weight; group three received NaF at a dosage of 10 mg/kg/body weight; and group four received NaF and NMO. The rats were orally administrated daily for a duration of eight weeks. The study's findings demonstrated that, in comparison to rats exposed to NaF alone, co-administration of NMO and NaF enhanced sperm motility and viability, decreased sperm morphological changes, restored the balance between oxidant and antioxidant status, improved testosterone and dehydroepiandrosterone, improved testicular histology, raised the Johnson score, and upregulated the StAR gene in testicular tissue. These findings show that NMO is promise as a prophylactic medication against sodium fluoride-induced testicular damage because administration of NMO had no adverse effects and enhanced reproductive health.


Assuntos
Moringa oleifera , Moringa , Animais , Masculino , Ratos , Peso Corporal , Regulação para Baixo , Fluoretos/metabolismo , Fluoretos/farmacologia , Moringa/metabolismo , Moringa oleifera/metabolismo , Estresse Oxidativo , Ratos Wistar , Sementes/metabolismo , Fluoreto de Sódio/metabolismo , Fluoreto de Sódio/farmacologia , Motilidade dos Espermatozoides , Esteroides/metabolismo , Esteroides/farmacologia , Testículo/metabolismo , Testosterona/metabolismo
5.
Birth Defects Res ; 115(6): 614-632, 2023 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-36751045

RESUMO

One of the disinfection byproducts of chlorinating drinking water is chloroacetonitrile (CAN). Thirty-six female rats were used and distributed equally into four groups. The low dose treated group received CAN at a dose of 5.5 mg/kg body weight/day (1/40 LD50 ) orally from the 6th to 12th day of gestation. The high dose treated group received 11 mg/kg body weight/day (1/20 LD50 ) of CAN orally for the same period, the vehicle control group received 1 mL of corn oil, and the water control group received 1 mL of distilled water orally for the same period. High dose exposure to CAN significantly reduced gravid uterine weight, fetal body weights, and length, and caused obvious skeletal deformities, weak mineralization. Fetal tibial growth plates displayed histopathologic changes. Induced oxidative stress and redox imbalance in fetal liver tissues was evidenced by significantly decreased in catalase and superoxide dismutase activity, and elevated malondialdehyde levels. Histopathological, glycogen content changes, and DNA damage were observed in the fetal liver of high dose treated group. Additionally, administration of high dose of CAN induced apoptosis, evidenced by increased caspase-3 concentration in fetal liver. Thus, extensive exposure to CAN induces poor pregnancy outcomes. CAN levels in water should be monitored regularly.


Assuntos
Apoptose , Estresse Oxidativo , Gravidez , Ratos , Feminino , Animais , Dano ao DNA , Fígado/patologia , Peso Corporal
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