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荷瘤动物的蛋白质摄入量与5-氟尿嘧啶毒性

Protein intake and 5-fluorouracil toxicity in tumor-bearing animals.

作者信息

Torosian M H, Jalali S, Nguyen H Q

机构信息

Department of Surgery, University of Pennsylvania School of Medicine, Philadelphia.

出版信息

J Surg Res. 1990 Oct;49(4):298-301. doi: 10.1016/0022-4804(90)90024-v.

Abstract

The administration of chemotherapy is limited in clinical situations by lack of selective antineoplastic activity resulting in significant host toxicity. Although it has been suggested that nutrition support can reduce chemotherapy-related toxicity, few controlled studies exist to document this clinical impression. This study was performed to determine the effect of enteral protein intake on 5-fluorouracil toxicity in tumor-bearing animals. Seventy-nine female Lewis/Wistar rats with subcutaneous mammary tumor implants (AC-33) were randomized to receive either standard protein (22.0% protein; 4.27 kcal/g) or an isocaloric, protein-depleted diet (0.03% protein; 4.20 kcal/g). One-half of the animals in each group received daily injections of 5-fluorouracil (15- or 25 mg/kg ip) or placebo (saline) for 4 or 5 days. Standard protein intake significantly increased host body weight and decreased leukopenia at low (15 mg/kg) and high (25 mg/kg) 5-fluorouracil therapy. At high-dose 5-Fluorouracil (25 mg/kg), the incidence and duration of diarrhea were decreased in animals receiving standard protein intake. Thus, enteral protein intake significantly reduced clinical and objective 5-fluorouracil toxicity and improved body weight in this tumor-bearing animal model.

摘要

化疗在临床应用中受到限制,因为缺乏选择性抗肿瘤活性,会导致明显的宿主毒性。尽管有人提出营养支持可以降低化疗相关毒性,但很少有对照研究能证实这一临床印象。本研究旨在确定肠内蛋白质摄入量对荷瘤动物5-氟尿嘧啶毒性的影响。将79只皮下植入乳腺肿瘤(AC-33)的雌性Lewis/Wistar大鼠随机分为两组,分别给予标准蛋白质饮食(蛋白质含量22.0%;4.27千卡/克)或等热量、低蛋白饮食(蛋白质含量0.03%;4.20千卡/克)。每组动物中有一半每天注射5-氟尿嘧啶(15或25毫克/千克,腹腔注射)或安慰剂(生理盐水),持续4或5天。在低剂量(15毫克/千克)和高剂量(25毫克/千克)5-氟尿嘧啶治疗时,标准蛋白质摄入量显著增加宿主体重并减少白细胞减少。在高剂量5-氟尿嘧啶(25毫克/千克)时,接受标准蛋白质摄入量的动物腹泻的发生率和持续时间降低。因此,在这个荷瘤动物模型中,肠内蛋白质摄入量显著降低了5-氟尿嘧啶的临床和客观毒性,并改善了体重。

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