Yadav P, Sarkar S, Bhatnagar D
Department of Biochemistry, D.A. University, Khandwa Road, INDORE, 452001, India.
Pharmacol Res. 1997 Sep;36(3):221-8. doi: 10.1006/phrs.1997.0222.
Alloxan-induced diabetic rats were treated with insulin (i.p.) or with Capparis decidua powder as a hypoglycaemic agent mixed with diet. The effect was assessed on lipid peroxidation (LPO) and the antioxidant defense system in rat tissues. The increased levels of blood glucose in diabetes produce superoxide anions and hydroxyl radicals in the presence of transition metal ions which cause oxidative damage to cell membranes. The heart tissue showed an increased lipid peroxidation (LPO) in diabetic rats while no significant change was observed in the liver and kidney. The treatment with C. decidua lowered LPO in these tissues even more effectively than insulin-treated rats. The superoxide dismutase (SOD) activity increased in the heart and kidneys in the diabetic group of rats probably to increase dismutation of superoxide anions. However, treatment with C. decidua decreased SOD activity in the liver and kidney and was comparable to control rats. Catalase (CAT) activity was not significantly affected in any of the tissues in diabetic and insulin-treated animals, however, CAT activity markedly increased in tissues with C. decidua treatment. Total and Se-dependent glutathione peroxidase (GSH-Px) in the heart was markedly lowered in diabetic rats which recovered with insulin as well as with C. decidua treatment. The increase in GSH-Px and CAT activity with C. decidua treatment may lower H2O2 toxicity and reduce oxidative stress in diabetes. However, glutathione (GSH) content in the heart and kidney and glutathione reductase (GSH-R) activity in all the tissues studied increased in diabetic rats while treatment with insulin lowered GSH content and GSH-R activity in these tissues. The treatment with C. decidua also decreased GSH-R activity in the kidney and heart which resulted in the decrease in GSH content in these tissues. The changes such as the increase in kidney and heart SOD may be an adaptive response in order to neutralize superoxide anions. The increase in GSH content and GSH-R activity in the tissue are in response to neutralize superoxide anions and to counteract oxidative stress in diabetes. Glutathione S-transferase (GST) was not significantly affected in diabetic rat tissue, however, heart GST increased with antidiabetic treatments. The increase in glucose-6-phosphate dehydrogenase (G6PDH) in the kidney and heart of diabetic rats subsequently decreased with C. decidua treatment. The increase in G6PDH in tissues may increase NADPH generation required for GSH-R activity and GSH production. It is suggested that these changes initially counteract the oxidative stress in diabetes, however, a gradual decrease in the antioxidative process may be one of the factors which results in chronic diabetes. The data indicate that C. decidua may have potential use as an antidiabetic agent and in lowering oxidative stress in diabetes.
用四氧嘧啶诱导糖尿病大鼠，分别腹腔注射胰岛素或在饮食中添加刺山柑粉末作为降血糖剂进行治疗。评估其对大鼠组织中脂质过氧化（LPO）和抗氧化防御系统的影响。糖尿病状态下血糖水平升高，在过渡金属离子存在时会产生超氧阴离子和羟基自由基，从而对细胞膜造成氧化损伤。糖尿病大鼠的心脏组织脂质过氧化（LPO）水平升高，而肝脏和肾脏未观察到显著变化。用刺山柑治疗比胰岛素治疗更有效地降低了这些组织中的LPO。糖尿病组大鼠心脏和肾脏中的超氧化物歧化酶（SOD）活性增加，可能是为了增加超氧阴离子的歧化作用。然而，用刺山柑治疗降低了肝脏和肾脏中的SOD活性，与对照大鼠相当。糖尿病和胰岛素治疗的动物各组织中过氧化氢酶（CAT）活性均未受到显著影响，然而，用刺山柑治疗的组织中CAT活性显著增加。糖尿病大鼠心脏中的总谷胱甘肽过氧化物酶和硒依赖性谷胱甘肽过氧化物酶（GSH-Px）显著降低，胰岛素治疗以及刺山柑治疗均可使其恢复。用刺山柑治疗使GSH-Px和CAT活性增加，可能会降低糖尿病中过氧化氢（H2O2）的毒性并减轻氧化应激。然而，糖尿病大鼠心脏和肾脏中的谷胱甘肽（GSH）含量以及所有研究组织中的谷胱甘肽还原酶（GSH-R）活性均增加，而胰岛素治疗降低了这些组织中的GSH含量和GSH-R活性。用刺山柑治疗也降低了肾脏和心脏中的GSH-R活性，导致这些组织中GSH含量降低。肾脏和心脏中SOD的增加等变化可能是一种适应性反应，以中和超氧阴离子。组织中GSH含量和GSH-R活性的增加是为了中和超氧阴离子并对抗糖尿病中的氧化应激。糖尿病大鼠组织中的谷胱甘肽S-转移酶（GST）未受到显著影响，然而，抗糖尿病治疗使心脏GST增加。糖尿病大鼠肾脏和心脏中葡萄糖-6-磷酸脱氢酶（G6PDH）增加，随后用刺山柑治疗使其降低。组织中G6PDH的增加可能会增加GSH-R活性和GSH生成所需的烟酰胺腺嘌呤二核苷酸磷酸（NADPH）的产生。提示这些变化最初可对抗糖尿病中的氧化应激，然而，抗氧化过程的逐渐减弱可能是导致慢性糖尿病的因素之一。数据表明，刺山柑可能具有作为抗糖尿病药物以及降低糖尿病中氧化应激的潜在用途。
