Abnosi Mohammad Hussein, Tabandeh Mohammad Reza, Mosavi-Aroo Fatmeh
Biology Department, Faculty of Sciences, Arak University, Arak, Iran.
Department of Biochemistry and Molecular Biology, Faculty of Veterinary Medicine, Shahid Chamran University, Ahwaz, Iran.
Reprod Fertil Dev. 2023 Mar;35(6):395-405. doi: 10.1071/RD22247.
In diabetes, abnormalities of granulosa cells (GCs) and steroidogenesis are associated with hyperglycaemia-induced oxidative stress. Betaine has beneficial effect in experimental model of diabetes by reducing oxidative stress, inflammation, and apoptosis.
In this study we investigate the effects of betaine to prevent oxidative stress in GCs induced by high glucose and improve steroidogenesis.
Primary GCs, isolated from ovarian follicles of C57BL/6 mice were cultured in 5mM (control) and 30mM (hyperglycaemia) of glucose and in presence of 5mM of betaine for 24h. Then antioxidant enzymes, malondialdehyde, oestradiol and progesterone were measured. In addition, the expression of Nrf2 and NF-κB , antioxidant enzymes (Sod1 , Gpx and Cat ) were analysed by qRT-PCR assay.
We observed significant (P <0.001) up-regulation of NF-κB and down-regulation of Nrf2 due to high concentration of glucose. Also significant (P <0.001) down-regulation of related antioxidant genes (Cat , Sod1 and GPx ) and activity reduction of these enzymes as well as significant (P <0.001) elevation of malondialdehyde was observed. In addition, betaine treatment compensated the drastic effect of high glucose induced oxidative stress via down-regulating the expression of NF-κB and up-regulating the expression of Nrf2 , Cat , Sod1 and GPx . It was also shown that betaine in the presence of FSH significantly (P <0.001) restored the oestradiol and progesterone level.
Betaine compensated the antioxidant stress in mouse GCs under hyperglycaemic condition via regulation of Nrf2/NF-κB at transcription level.
As betaine is a natural product and no side effect has been reported to today, we suggest more research needs to be carried out especially on patients whom suffer from diabetes to find the probability of using betaine as a therapeutic agent.
在糖尿病中，颗粒细胞（GCs）异常和类固醇生成与高血糖诱导的氧化应激有关。甜菜碱通过降低氧化应激、炎症和细胞凋亡，在糖尿病实验模型中具有有益作用。
在本研究中，我们调查甜菜碱预防高糖诱导的GCs氧化应激和改善类固醇生成的作用。
从C57BL/6小鼠卵巢卵泡中分离出的原代GCs，在5mM（对照）和30mM（高血糖）葡萄糖中培养，并在存在5mM甜菜碱的情况下培养24小时。然后测量抗氧化酶、丙二醛、雌二醇和孕酮。此外，通过qRT-PCR分析Nrf2和NF-κB的表达以及抗氧化酶（Sod1、Gpx和Cat）的表达。
我们观察到由于高浓度葡萄糖导致NF-κB显著上调（P<0.001）和Nrf2下调。还观察到相关抗氧化基因（Cat、Sod1和GPx）显著下调（P<0.001）以及这些酶的活性降低，同时丙二醛显著升高（P<0.001）。此外，甜菜碱处理通过下调NF-κB的表达和上调Nrf2、Cat、Sod1和GPx的表达，补偿了高糖诱导的氧化应激的剧烈影响。还表明，在促卵泡激素存在的情况下，甜菜碱显著恢复了雌二醇和孕酮水平（P<0.001）。
甜菜碱通过在转录水平调节Nrf2/NF-κB，补偿了高血糖条件下小鼠GCs中的抗氧化应激。
由于甜菜碱是一种天然产物，且至今未报道有副作用，我们建议尤其需要对糖尿病患者进行更多研究，以确定使用甜菜碱作为治疗剂的可能性。
