Cleistanthus collinus is a poisonous shrub used for deliberate self-harm in rural areas of South India and intake of boiled decoction of leaves is a common method of self-harm. Distal renal tubular acidosis (dRTA) is an important clinical symptom observed in C. collinus poisoning, and renal V-ATPases may be potential targets of damage. However, a lack of understanding of molecular mediators involved hampers medical management, which is mainly supportive. We hypothesized that C. collinus poisoning induces renal oxidative stress; probably by inducing mitochondrial uncoupling, which compromises V-ATPase activity to ultimately produce dRTA. This was tested by exposing renal BBMV, kidney cells in culture, and Wistar rats to C. collinus poisoning. Exposure to C. collinus aqueous extract resulted in significant elevations in the lipid peroxidation marker, conjugated dienes, in cell culture and in vivo. A significant decrease in mitochondrial respiratory control ratio was observed in kidneys from C. collinus-treated animals suggesting that mitochondrial oxidative phosphorylation is uncoupled. This was accompanied by significant increase in ADP levels and a decrease in proton pump activity. Thus, these results demonstrate that C. collinus poisoning induces oxidative stress which influences proton pump activity, probably due to feedback inhibition by elevated ADP levels because of mitochondrial dysfunction in the rat kidney.

Cleistanthus collinus是一种有毒灌木，用于在印度南部农村地区有意进行自我伤害，摄入煮沸的叶子水煎剂是一种常见的自我伤害方法。远端肾小管性酸中毒（dRTA）是在柯氏梭菌中毒中观察到的重要临床症状，肾脏V-ATPases可能是潜在的损伤靶标。但是，由于缺乏对分子介体的了解，因此妨碍了医疗管理，这主要是对医疗管理的支持。我们假设C. collinus中毒会诱发肾脏氧化应激。可能是通过诱导线粒体解偶联，从而破坏了V-ATPase活性最终产生了dRTA。通过将肾BBMV，培养的肾细胞和Wistar大鼠暴露于C. collinus进行测试中毒。暴露于C. collinus水提取物会导致脂质过氧化标记物，共轭二烯在细胞培养和体内显着升高。在来自C. collinus处理的动物的肾脏中观察到线粒体呼吸控制比的显着降低，表明线粒体的氧化磷酸化是不耦合的。这伴随着ADP水平的显着增加和质子泵活性的降低。因此，这些结果表明，结肠念珠菌中毒诱导氧化应激，该氧化应激影响质子泵的活性，这可能是由于大鼠肾脏中线粒体功能障碍引起的ADP水平升高引起的反馈抑制。