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链脲佐菌素和四氧嘧啶诱导大鼠B细胞损伤的机制。

Mechanisms of streptozotocin- and alloxan-induced damage in rat B cells.

作者信息

Wilson G L, Patton N J, McCord J M, Mullins D W, Mossman B T

出版信息

Diabetologia. 1984 Dec;27(6):587-91. doi: 10.1007/BF00276973.

DOI:10.1007/BF00276973
PMID:6241574
Abstract

In studies to evaluate possible inhibitors of the B-cell toxin, streptozotocin, the superoxide scavenger, superoxide dismutase, did not prevent or reduce the toxic effects of streptozotocin as determined by loss of insulin secretion from rat pancreatic B cells in monolayer culture. However, 1,1-dimethyl urea, a scavenger of the hydroxyl radical, did afford significant protection. Both scavengers diminished the cytotoxic effects of alloxan. The inhibitors of poly (ADP-ribose) synthetase, 3-aminobenzamide and nicotinamide, also were effective in attenuating alloxan- and streptozotocin-induced B-cell toxicity. Tests of the hydroxyl-scavenging ability of the three streptozotocin antagonists revealed that 3-aminobenzamide, nicotinamide and 1,1-dimethyl urea were effective scavengers of this free radical. Conversely, 1,1-dimethyl urea, although not as potent as 3-aminobenzamide or nicotinamide, was found to inhibit poly (ADP-ribose) synthetase. These data indicate that these chemicals most likely attenuate alloxan-induced toxicity by scavenging the hydroxyl radical and diminish streptozotocin-induced toxicity by inactivation of the poly (ADP-ribose) system.

摘要

在评估B细胞毒素链脲佐菌素可能的抑制剂的研究中,超氧化物清除剂超氧化物歧化酶并不能预防或降低链脲佐菌素的毒性作用,这是通过单层培养的大鼠胰腺B细胞胰岛素分泌丧失来确定的。然而,羟自由基清除剂1,1 - 二甲基脲确实提供了显著的保护作用。两种清除剂都减弱了四氧嘧啶的细胞毒性作用。聚(ADP - 核糖)合成酶抑制剂3 - 氨基苯甲酰胺和烟酰胺在减轻四氧嘧啶和链脲佐菌素诱导的B细胞毒性方面也有效。对三种链脲佐菌素拮抗剂的羟自由基清除能力的测试表明,3 - 氨基苯甲酰胺、烟酰胺和1,1 - 二甲基脲是这种自由基的有效清除剂。相反,虽然1,1 - 二甲基脲不如3 - 氨基苯甲酰胺或烟酰胺有效,但发现它能抑制聚(ADP - 核糖)合成酶。这些数据表明,这些化学物质最有可能通过清除羟自由基来减轻四氧嘧啶诱导的毒性,并通过使聚(ADP - 核糖)系统失活来降低链脲佐菌素诱导的毒性。

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Mechanisms of streptozotocin- and alloxan-induced damage in rat B cells.链脲佐菌素和四氧嘧啶诱导大鼠B细胞损伤的机制。
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5
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J Biol Chem. 1982 Jun 10;257(11):6084-8.
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