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脂质体钆-二乙三胺五乙酸的详细毒性研究。

Detailed toxicity studies of liposomal gadolinium-DTPA.

作者信息

Fritz T, Unger E, Wilson-Sanders S, Ahkong Q F, Tilcock C

机构信息

Department of Radiology, University of Arizona Health Sciences Center, Tucson 85724.

出版信息

Invest Radiol. 1991 Nov;26(11):960-8. doi: 10.1097/00004424-199111000-00007.

DOI:10.1097/00004424-199111000-00007
PMID:1835967
Abstract

Acute, subacute, and delayed toxicity testing was assessed in mice for liposomal gadolinium-DTPA (Gd-DTPA), blank liposomes, and nonliposomal Gd-DTPA. In the subacute experiments mice were injected intravenously (IV) with 0.3 mmol/kg Gd-DTPA per day for 30 days in the form of either free Gd-DTPA, liposomal Gd-DTPA, or an equivalent amount of lipid in blank liposomes without Gd-DTPA. The interpolated acute LD50 of liposomal and nonliposomal Gd-DTPA, estimated as a means of identifying the approximate level, was similar (LD50 = 5.7 mmol/kg Gd-DTPA). In subacute toxicity testing, prolonged high doses of liposomal Gd-DTPA caused splenomegaly, cardiomegaly, lymphocytopenia and hypergammaglobulinemia (P less than .05). Nonliposomal Gd-DTPA caused mild cardiomegaly and altered liver enzymes (P less than .05). Blank liposomes caused relatively mild splenomegaly (P less than .05) but few other changes. Delayed testing three months after the subacute testing showed that most of the changes caused by the liposomal Gd-DTPA were reversible.

摘要

对小鼠进行了脂质体钆-二乙三胺五乙酸(Gd-DTPA)、空白脂质体和非脂质体Gd-DTPA的急性、亚急性和延迟毒性测试。在亚急性实验中,以游离Gd-DTPA、脂质体Gd-DTPA或不含Gd-DTPA的空白脂质体中等量脂质的形式,每天给小鼠静脉注射(IV)0.3 mmol/kg Gd-DTPA,持续30天。脂质体和非脂质体Gd-DTPA的内插急性半数致死量(LD50)估计相似(LD50 = 5.7 mmol/kg Gd-DTPA),以此作为确定大致水平的一种方法。在亚急性毒性测试中,长期高剂量的脂质体Gd-DTPA导致脾肿大、心脏肥大、淋巴细胞减少和高球蛋白血症(P < 0.05)。非脂质体Gd-DTPA导致轻度心脏肥大和肝酶改变(P < 0.05)。空白脂质体导致相对轻度的脾肿大(P < 0.05),但其他变化很少。亚急性测试三个月后的延迟测试表明,脂质体Gd-DTPA引起的大多数变化是可逆的。

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