Adisa R A, Ajewole I, Omolohunnu I, Olorunsogo O O
Laboratories for Biomembrane Research and Biotechnology, Department of Biochemistry, College of Medicine, University of Ibadan, Ibadan, Nigeria.
Afr J Med Med Sci. 2010 Dec;39 Suppl:129-38.
Apoptosis involves a phenomenon termed mitochondrial permeability transition (MPT) which induces permeability of a voltage-dependent pore to solutes of smaller than 1500Da. Induction of MPT pore is beneficial in case of tumour cells while inhibition of the pore is relevant in conditions such as tissue wastage. The effects of methanol extracts of Buccholzia coriacea (MEBC) commonly known as 'wonder kola' on MPT wa s assessed in vitro in normal rats inthe presence and absence of exogenous calcium- the triggering agent. MPT was estimated by the extent of mitochondrial swelling monitored spectrophotometrically as decreases in absorbance at 540nm. The results revealed that in the absence ofexogenous calcium, MPT pore opening was induced by MEBC at 200 microg/ml, 600 microg/ml, 1000 microg/ml and 1400 microg/ml in a concentration-dependent manner by 21.0, 7.6, 4.2, 3.5 folds, although higher concentrations of MEBC reduced pore opening. Pre-incubation of mitochondria with similar concentrations of MEBC for 5 minutes in the absence of calcium induced pore opening by 1.47, 10, 8.7 and 10.1 folds, respectively. Furthermore, mitochondrial membrane treated with MEBC (200 microg/ml, 600 microg/ml, 1000 microg/ml and 1400 microg/ml) in the presence of exogenous calcium induced pore opening by 63.9%, 44.0%, 23.4% and 64.4%, respectively. Oral administration of MEBC at varying doses of 50 - 200mg/kg b.w to rats for 30 days had no significant effects (p>0.05) on MPT pore opening in the absence of calcium when compared to untreated animals. The liver function tests revealed that the activities of alanine and aspartate amino transferases, alkaline phosphatase, and ã-glutammyl transferase were significantly (p>0.05) increased in serum of animals exposed to MEBC compared to control animals. Overall, Buccholzia coriacea induced MPT pore opening in vitro thus suggesting that certain bioactive components in the extract may prove useful in chemotherapy of tumor cells however, these bioactive agents seem to have been completely metabolized in vivo.
细胞凋亡涉及一种称为线粒体通透性转换(MPT)的现象,它会诱导电压依赖性孔对分子量小于1500Da的溶质产生通透性。MPT孔的诱导在肿瘤细胞情况下是有益的,而在诸如组织消耗等情况下抑制该孔则具有重要意义。在正常大鼠体外评估了俗称“神奇可乐”的厚叶布枯甲醇提取物(MEBC)对MPT的影响,实验分别在有和没有外源性钙(触发剂)的情况下进行。通过分光光度法监测线粒体肿胀程度来估计MPT,即通过540nm处吸光度的降低来衡量。结果显示,在没有外源性钙的情况下,MEBC在200μg/ml、600μg/ml、1000μg/ml和1400μg/ml浓度下以浓度依赖性方式诱导MPT孔开放,分别增加了21.0倍、7.6倍、4.2倍和3.5倍,尽管更高浓度的MEBC会减少孔开放。在没有钙的情况下,用相似浓度的MEBC对线粒体进行5分钟预孵育,分别诱导孔开放1.47倍、10倍、8.7倍和10.1倍。此外,在有外源性钙存在的情况下,用MEBC(200μg/ml、600μg/ml、1000μg/ml和1400μg/ml)处理线粒体膜分别诱导孔开放63.9%、44.0%、23.4%和64.4%。与未处理的动物相比,以50 - 200mg/kg体重的不同剂量给大鼠口服MEBC 30天,在没有钙的情况下对MPT孔开放没有显著影响(p>0.05)。肝功能测试显示,与对照动物相比,暴露于MEBC的动物血清中丙氨酸和天冬氨酸转氨酶、碱性磷酸酶以及γ-谷氨酰转移酶的活性显著升高(p>0.05)。总体而言,厚叶布枯在体外诱导MPT孔开放,因此表明提取物中的某些生物活性成分可能在肿瘤细胞化疗中有用,然而,这些生物活性剂似乎在体内已被完全代谢。