Ulusu Nuray Nuriye, Gök Müslüm, Sayin Şakul Arzu Ayşe, Ari Nuray, Stefek Milan, Karasu Çimen
Department of Medical Biochemistry, School of Medicine, Koc University, Istanbul, Turkey.
Department of Biochemistry, Faculty of Medicine, Hacettepe University, Ankara, Turkey.
Interdiscip Toxicol. 2017 Dec;10(4):148-154. doi: 10.1515/intox-2017-0021. Epub 2018 Mar 1.
The pentose phosphate pathway and glutathione-associated metabolism are the main antioxidant cellular defense systems. This study investigated the effects of the powerful antioxidant SMe1EC2 (2-ethoxycarbonyl-8-methoxy-2,3,4,4a,5,9b-hexahydro-1H-pyrido[4,3-b] indolinium dichloride) on pentose phosphate pathway (PPP) and glutathione-dependent enzyme activities in aged diabetic and aged matched control rats. Diabetes was induced by streptozotocin injection in rats aged 13-15 months. Diabetic and control rats were divided into two subgroups, one untreated and one treated with SMe1EC2 (10 mg/kg/day, orally) for 4 months. SMe1EC2 ameliorated body weight loss, but not hyperglycemia of aged diabetic rats. Diabetes resulted in decreased glucose-6-phosphate dehydrogenase (G6PD), 6-phosphogluconate dehydrogenase (6PGD) and glutathione-S-transferase (GST), yet in unchanged glutathione reductase (GR) in the liver of aged diabetic rats. In the liver of the aged control rats, SMe1EC2 did not affect G6PDH, 6PGDH and GR, but it inhibited GST. SMe1EC2 also failed to affect diabetes-induced decline in 6PGDH, it ameliorated G6PDH but produced further decline in GST in the liver of aged diabetic rats. In the kidney of aged rats, G6PDH and GST were found to be comparable among the groups, but diabetes up-regulated 6PGDH and GR; these alterations were prevented by SMe1EC2. In the heart of aged diabetic rats, while GST remained unchanged, the recorded increase in G6PD, 6PGD, GR was prevented by SMe1EC2. Furthermore, an unchanged GR and remarkable increases in G6PD, 6PGD and GST were found in the lung of the aged diabetic group. These alterations were completely prevented by SMe1EC2. The results suggest that in aged rats SMe1EC2 can ameliorate the response of the kidney, heart and lung but not that of the liver against diabetes-induced glucotoxicity by interfering with the activity of redox network enzymes.
磷酸戊糖途径和谷胱甘肽相关代谢是细胞主要的抗氧化防御系统。本研究调查了强效抗氧化剂SMe1EC2（2-乙氧羰基-8-甲氧基-2,3,4,4a,5,9b-六氢-1H-吡啶并[4,3-b]吲哚二氯化物）对老年糖尿病大鼠和年龄匹配的对照大鼠磷酸戊糖途径（PPP）及谷胱甘肽依赖性酶活性的影响。通过给13 - 15月龄大鼠注射链脲佐菌素诱导糖尿病。糖尿病大鼠和对照大鼠分为两个亚组，一组不治疗，另一组用SMe1EC2（10 mg/kg/天，口服）治疗4个月。SMe1EC2改善了老年糖尿病大鼠的体重减轻，但未改善高血糖。糖尿病导致老年糖尿病大鼠肝脏中葡萄糖-6-磷酸脱氢酶（G6PD）、6-磷酸葡萄糖酸脱氢酶（6PGD）和谷胱甘肽-S-转移酶（GST）降低，但谷胱甘肽还原酶（GR）不变。在老年对照大鼠肝脏中，SMe1EC2不影响G6PDH、6PGDH和GR，但抑制GST。SMe1EC2也未能影响糖尿病诱导的老年糖尿病大鼠肝脏中6PGDH的下降，它改善了G6PDH，但使GST进一步下降。在老年大鼠肾脏中，各实验组间G6PDH和GST相当，但糖尿病上调了6PGDH和GR；这些改变被SMe1EC2阻止。在老年糖尿病大鼠心脏中，虽然GST不变，但SMe1EC2阻止了记录到的G6PD、6PGD、GR的增加。此外，老年糖尿病组肺中GR不变，G6PD、6PGD和GST显著增加。这些改变被SMe1EC2完全阻止。结果表明，在老年大鼠中，SMe1EC2可通过干扰氧化还原网络酶的活性，改善肾脏、心脏和肺对糖尿病诱导的糖毒性的反应，但不能改善肝脏的反应。
