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1.
Toxicol Appl Pharmacol ; 489: 117009, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38906509

RESUMO

INTRODUCTION: Aripiprazole (ARI) is a recently developed antipsychotic medication that belongs to the second generation of antipsychotics. The literature has contradictory information regarding ARI, which has been classified as pregnant use category C by the FDA. METHODS: 125 pathogen-free fertilized eggs were incubated for 28 h and divided into five groups of 25 eggs each (including the control group), and 18 eggs with intact integrity were selected from each group. After the experimental groups were divided, ARI was administered subblastodermally with a Hamilton micro-injector at 4 different doses (1 mg/kg, 5 mg/kg, 10 mg/kg, 20 mg/kg). At the 48th hour of incubation, all eggs were hatched and embryos were removed from the embryonic membranes. And then morphologic (position of the neural tube (open or closed), crown-rump length, number of somites, embryological development status), histopathologic (apoptosis (caspase 3), cell proliferation (PCNA), in situ recognition of DNA breaks (tunnel)), genetic (BRE gene expression) analyzes were performed. RESULTS: According to the results of the morphological analysis, when the frequency of neural tube patency was evaluated among the experimental groups, a statistically significant difference was determined between the control group and all groups (p < 0.001). In addition, the mean crown-rump length and somite number of the embryos decreased in a dose-dependent manner compared to the control group. It was determined that mRNA levels of the BRE gene decreased in embryos exposed to ARI compared to the control group (p < 0.001). CONCLUSION: Morphologically, histopathologically, and genetically, aripiprazole exposure delayed neurogenesis and development in early chick embryos. These findings suggest its use in pregnant women may be teratogenic. We note that these results are preliminary for pregnant women, but they should be expanded and studied with additional and other samples.


Assuntos
Aripiprazol , Tubo Neural , Animais , Aripiprazol/toxicidade , Tubo Neural/efeitos dos fármacos , Embrião de Galinha , Antipsicóticos/toxicidade , Apoptose/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Desenvolvimento Embrionário/efeitos dos fármacos , Relação Dose-Resposta a Droga , Regulação da Expressão Gênica no Desenvolvimento/efeitos dos fármacos , Antígeno Nuclear de Célula em Proliferação/metabolismo , Caspase 3/metabolismo , Caspase 3/genética
2.
Mol Vis ; 29: 245-255, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38222446

RESUMO

PURPOSE: Cataract, which occurs as a result of lens opacification, is one of the most common causes of vision loss. In the literature, deterioration of the antioxidant system due to the increase in reactive oxygen species and oxidant levels is shown among the causes of cataract formation. The aim of this study was to investigate the antioxidant effect of chrysin on steroid-induced cataract development in an experimental chick embryo model using morphological, histological and biochemical parameters. METHODS: Within the scope of the study, 150 specific pathogen free (SPF) fertilized eggs were used. Eggs were divided into 6 groups as control (group 1), corn oil (group 2), hydrocortisone hemisuccinate sodium (HC) (group 3), low dose chrysin (group 4), medium dose chrysin (group 5) and high dose chrysin (group 6). On the 15th day of incubation, Chrysin and HC were applicated to the air sac of the eggs with Hamilton and/or insulin injector. On day 17, the chick embryos were removed from the eggs and the bulbus oculi of the embryos were dissected. Lenses of 9 embryos were used for morpholigical cataract grading in each group, lens of 8 embryos for biochemical analysis and intact eyes of 7 embryos for histological evaluation (TUNEL method). RESULTS: No opacity was observed in any of the lenses in Group 1 and 2. Cataract was observed in all lenses in Group 3. The mean opacity grades in group 3 were statistically significantly higher when compared to group 1 and 2 (p<0.05). The difference between group 6 and group 3 was statistically significant (p<0.05). GSH and TAS levels in the lenses were statistically significantly decreased compared to the control group due to HC application (p<0.05). It was determined that the decreased GSH and TAS levels in the lenses increased in relation to the Chrysin application doses. The increased levels of MDA, TOS, caspase 3 and caspase 9 in the HC group decreased significantly depending to the chrysin doses (p<0.05). In addition, while the rate of apoptotic cells determined by the TUNEL method was statistically significantly higher in the HC administered group than in the control group (p<0.05), it was statistically significantly decreased in the chrysin-administered groups, in relation to the dose of chrysin (p<0.05). CONCLUSIONS: We think that anti-cataract effect of crhysin may be due to the antioxidant and antiapoptotic properties of chrysin. However, more research is needed to clarify the anti-cataract effects of chrysin.


Assuntos
Catarata , Cristalino , Animais , Embrião de Galinha , Antioxidantes/farmacologia , Catarata/induzido quimicamente , Catarata/tratamento farmacológico , Catarata/patologia , Cristalino/patologia , Flavonoides/farmacologia , Glutationa
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