RESUMO
Tripterygium wilfordii (TW) preparations have been utilized in China for treating rheumatoid arthritis and autoimmune diseases. However, their clinical use is limited due to reproductive toxicity, notably premature ovarian failure (POF). Our study aimed to investigate the effect and mechanism of bergenin in attenuating POF induced by triptolide in mice. POF was induced in female ICR mice via oral triptolide administration (50⯵g/kg) for 60 days. Mice received bergenin (25, 50, 100â¯mg/kg, i.g.) or estradiol valerate (EV) (0.1â¯mg/kg, i.g.) daily, 1â¯h before triptolide treatment. In vitro, ovarian granulosa cells (OGCs) were exposed to triptolide (100â¯nM) and bergenin (1, 3, 10⯵M). Antioxidant enzyme activity, protein expression, apoptosis rate, and reactive oxygen species (ROS) levels were assessed. The results showed that triptolide-treated mice exhibited evident atrophy, along with an increase in atretic follicles. Bergenin (50, 100â¯mg/kg) and EV (0.1â¯mg/kg), orally administered, exerted significant anti-POF effect. Bergenin and EV also decreased apoptosis in mouse ovaries. In vitro, bergenin (1, 3, 10⯵M) attenuated triptolide-induced OGCs apoptosis by reducing levels of apoptosis-related proteins. Additionally, bergenin reduced oxidative stress through downregulation of antioxidant enzymes activity and overall ROS levels. Moreover, the combined use with Sh-Nrf2 resulted in a reduced protection of bergenin against triptolide-induced apoptosis of OGCs. Together, bergenin counteracts triptolide-caused POF in mice by inhibiting Nrf2-mediated oxidative stress and preventing OGC apoptosis. Combining bergenin with TW preparations may effectively reduce the risk of POF.
Assuntos
Antioxidantes , Apoptose , Benzopiranos , Diterpenos , Compostos de Epóxi , Células da Granulosa , Camundongos Endogâmicos ICR , Fenantrenos , Insuficiência Ovariana Primária , Espécies Reativas de Oxigênio , Animais , Feminino , Insuficiência Ovariana Primária/induzido quimicamente , Insuficiência Ovariana Primária/tratamento farmacológico , Insuficiência Ovariana Primária/prevenção & controle , Diterpenos/farmacologia , Fenantrenos/toxicidade , Fenantrenos/farmacologia , Compostos de Epóxi/toxicidade , Antioxidantes/farmacologia , Apoptose/efeitos dos fármacos , Benzopiranos/farmacologia , Benzopiranos/uso terapêutico , Espécies Reativas de Oxigênio/metabolismo , Células da Granulosa/efeitos dos fármacos , Células da Granulosa/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Fator 2 Relacionado a NF-E2/metabolismo , Camundongos , Células CultivadasRESUMO
This article demonstrates an inductively coupled high-accuracy localization system for miniature ingestible devices. It utilizes an inductance double capacitances-series capacitance (LCC-S) compensation architecture that enables mutual inductance measurement at primary side that is positioned outside the human body and less constrained by power budget and size than the miniature ingestible. Depending on the secondary circuit architecture, only limited and simple cooperative measurements are needed from the ingestible secondary side, which saves power and area in the miniature device. The errors in the system are modeled thoroughly, providing insights about system require-ments for a particular localization accuracy target for efficient design and to identify key building blocks with large influence on overall performance. The model shows that sub-centimeter localization root-mean-square error (RMSE) can be achieved with a modest external ADC (18bit) using three primary coils and three secondary coils. The localization is verified along a complete small intestine tract with realistic dimensions. The proposed model is verified by simulation and experiment showing that at the selected frequency range up to 5 MHz the body has no influence on the accuracy. The use of 0.9% saline as phantom is proposed which guarantees the analysis validity for all body types.