Olowofolahan Adeola O, Oyebode Olubukola T, Olorunsogo Olufunso O
Laboratory for Membrane Biochemistry Research and Biotechnology, Department of Biochemistry, Faculty of Basic Medical Sciences, College of Medicine, University of Ibadan, Ibadan, Nigeria.
Toxicol Mech Methods. 2021 Jan;31(1):43-52. doi: 10.1080/15376516.2020.1827329. Epub 2020 Oct 6.
Early detection and treatment of endometrial hyperplasia (EH) is mandatory for endometrial cancer prevention. Several bioactive agents of plant origin have been shown to elicit their chemotherapeutic effect against tumors and cancer via induction of mitochondrial permeability transition(mPT) pore opening. This research was therefore aimed at evaluating the potential chemopreventive effect of methyl palmitate (MP), on estradiol benzoate(EB)-induced EH, looking at the mitochondrial-mediated pathway and other possible mechanisms of action. Mitochondria were isolated using differential centrifugation. The mPT pore, mitochondrial ATPase (mATPase) activity, lipid peroxidation and cytochrome c release were determined by standard methods using spectrophotometer. Uterine interleukin 1b, MDA levels and SOD, GSH activities, were determined using commercially available kits. The uterine histological and immunohistochemical assessment of estrogen receptor (ERα), IL-1b and caspas-3 were carried out. The fibroblast cell count density was determined using histomorphometry. At all the concentrations of MP used, there was no significant induction of mPT pore opening, neither any enhancement of mATPase activity nor release of cytochrome c when compared to the control. Similar pattern of results were recorded for the study. However, there was marked increase in the uterine MDA and interleukin 1b levels, with concurrent decrease in SOD and GSH activities, in the EB-treated group, which was significantly reversed by MP co-administration. Endometrial Hyperplasia observed in the EB-treated group was ameliorated by MP co-administration. The immunoexpression of ERα and IL-1b in the EB-treated group was reversed by MP co-administration. This study suggests anti-inflammatory, antioxidant and anti-proliferative potential of MP against EB-induced EH.
早期发现和治疗子宫内膜增生（EH）对于预防子宫内膜癌至关重要。几种植物源生物活性剂已被证明可通过诱导线粒体通透性转换（mPT）孔开放来发挥其对肿瘤和癌症的化疗作用。因此，本研究旨在评估棕榈酸甲酯（MP）对苯甲酸雌二醇（EB）诱导的EH的潜在化学预防作用，研究线粒体介导的途径和其他可能的作用机制。采用差速离心法分离线粒体。使用分光光度计通过标准方法测定mPT孔、线粒体ATP酶（mATP酶）活性、脂质过氧化和细胞色素c释放。使用市售试剂盒测定子宫白细胞介素1β、丙二醛（MDA）水平以及超氧化物歧化酶（SOD）、谷胱甘肽（GSH）活性。对雌激素受体（ERα）、白细胞介素1β和半胱天冬酶-3进行子宫组织学和免疫组织化学评估。使用组织形态计量学确定成纤维细胞计数密度。与对照组相比，在所有使用的MP浓度下，均未观察到mPT孔开放的显著诱导，mATP酶活性也未增强，细胞色素c也未释放。该研究记录了类似的结果模式。然而，在EB治疗组中，子宫MDA和白细胞介素1β水平显著升高，同时SOD和GSH活性降低，而MP共同给药可显著逆转这种情况。MP共同给药改善了EB治疗组中观察到的子宫内膜增生。MP共同给药逆转了EB治疗组中ERα和白细胞介素1β的免疫表达。本研究表明MP对EB诱导的EH具有抗炎、抗氧化和抗增殖潜力。
