MULTI-ORGAN METABOLIC PERTURBATION STUDY OF DEXTRAN SULFATE SODIUM-INDUCED ULCERATIVE COLITIS USING GLYCOLYTIC AND MITOCHONDRIAL METABOLIZING ENZYMES AS INDICES

Ulcerative colitis is an inflammatory bowel disease, which includes chronic inflammation of the gastrointestinal tract. Recent studies have suggested that the etiology of inflammatory bowel disease is multifactorial, resulting from the interplay of immunological, molecular, genetic, microbial, diet, drug use-related, and environmental factors. This study was designed to investigate multiple organ toxicity of Dextran sulfate sodium-induced (DSS) ulcerative colitis using glycolytic and mitochondrial metabolizing enzymes as indices Twelve mice were divided into two groups of six mice each. Group A (Control) received normal drinking water while group B was fed with 2.5% DSS for 7 days in their drinking water, and the dextran sulfate sodium solution was replenished daily. The liver, kidney, colon, spleen was excised from the mice after the last administration of DSS, glycolytic and mitochondrial metabolizing enzymes were assessed in all the organs and lymphocytes. Activities of glycolytic enzymes lactate dehydrogenase and NADase were down-regulated in all the organs. Hepatic hexokinase activity significantly reduced as opposed to the increase observed in other organs, while aldolase activities were up-regulated in all the organs. Furthermore, DSS administration caused perturbation in the activities of mitochondrial metabolizing enzymes in all the organs. Activities of succinate dehydrogenase, malate dehydrogenase, Combined Complexes I+III, II+III, and IV were down-regulated. All observations are relative to control. ata from this study demonstrated that administration of DSS induced ulcerative colitis which invariably perturbs the glycolytic enzymes while mitochondrial metabolizing enzymes are down-regulated leading to decreased energy availability for cellular processes during ulcerative colitis pathological condition.溃疡性结肠炎（Ulcerative Colitis）是一类炎症性肠病（Inflammatory Bowel Disease），涵盖胃肠道慢性炎症。现有研究表明，炎症性肠病的病因呈多因素特征，由免疫、分子、遗传、微生物、饮食、药物相关及环境等多种因素相互作用所致。本研究旨在以糖酵解及线粒体代谢酶为指标，探究葡聚糖硫酸钠（Dextran Sulfate Sodium, DSS）诱导的溃疡性结肠炎对多器官的毒性作用。将12只小鼠分为两组，每组6只。A组（对照组）给予正常饮用水，B组小鼠饮用含2.5% DSS的饮用水，持续7天，且每日更换DSS溶液。末次给予DSS后，处死小鼠并摘取肝脏、肾脏、结肠及脾脏，对所有器官及淋巴细胞中的糖酵解酶与线粒体代谢酶进行检测评估。结果显示，所有器官中的糖酵解酶乳酸脱氢酶（Lactate Dehydrogenase）与烟酰胺腺嘌呤二核苷酸酶（NADase）活性均呈下调趋势。与其他器官中活性升高的情况相反，肝脏己糖激酶（Hexokinase）活性显著降低，而所有器官中的醛缩酶（Aldolase）活性则均上调。此外，给予DSS可扰动所有器官中线粒体代谢酶的活性：琥珀酸脱氢酶（Succinate Dehydrogenase）、苹果酸脱氢酶（Malate Dehydrogenase）以及线粒体复合物I+III、II+III与IV的活性均出现下调，所有观测结果均以对照组为参照。本研究数据显示，给予DSS可诱导溃疡性结肠炎，该病理状态下糖酵解酶活性紊乱，同时线粒体代谢酶活性下调，最终导致细胞进程所需的能量可用性降低。