还原型谷胱甘肽增强恶性肿瘤化疗患者抗氧化能力的研究

背景与目的:还原型谷胱甘肽(reducedglutathione,GSH)对肿瘤化疗患者的影响尚未明了,本研究观察GSH对恶性肿瘤化疗患者的脂质过氧化和抗氧化酶活性的作用。方法:62例肿瘤化疗患者随机自身交叉分为AB和BA组,AB组第1周期为化疗加GSH治疗,第2周期单纯化疗;BA组第1周期单纯化疗,第2周期为化疗加GSH治疗。每21～28天为1个周期,每次化疗持续2～5天,依不同化疗方案而不同。GSH用法为1500mg·(m2·d)-1,静脉滴注15min,从化疗第1天用起,每天1次,连用7天。于化疗前、化疗第7、28天(或每21天为1个化疗周期者,改为第21天)检测患者血清丙二醛(malondialdehyde,MDA)浓度、超氧化物歧化酶总活力(totalsuperoxidedismutase,T-SOD)、谷胱甘肽过氧化物酶(glutathioneperoxidase,GSH-Px)活力。结果:(1)单纯化疗第7天与化疗前相比,血清MDA浓度明显升高,分别为(6.12±1.94)μmol/L与(4.63±1.87)μmol/L(P<0.01),在第28天(或第21天)时下降至(5.05±2.07)μmol/L,但仍高于化疗前(P<0.05)。(2)单纯化疗第7天与化疗前相比,T-SOD、GSH-Px活力水平明显降低(P<0.01),在第28天(或第21天)时部分恢复,但低于化疗前(P<0.05,P<0.01)。(3)化疗加GSH治疗能明显减轻化疗引起的脂质过氧化,并能明显减轻化疗引起的抗氧化酶活性的下降。(4)在AB

Enhancement of antioxidant capability of cancer patients during chemotherapy by reduced glutathione

BACKGROUND & OBJECTIVE: It is unknown how administration of reduced glutathione (GSH) affects chemotherapy of cancer patients. This study was designed to investigate the effect of GSH on lipid peroxidation, and activities of antioxidant enzyme among cancer patients with chemotherapy. METHODS: Sixty-two cancer patients with chemotherapy were enrolled randomly into AB or BA group in cross-over pattern. In AB group, combination of chemotherapy and GSH was administrated first, then following chemotherapy alone was given 21 or 28 days later. In group BA, chemotherapy alone was administrated first, then the combination therapy was given. Duration of chemotherapy was 2-5 days, 21-28 days for a cycle, depended on chemotherapy strategies. GSH was given as a 15 minute intravenous infusion at the dose of 1 500 mgx(m(2)xd)(-1) for 7 days from day 1. Serum samples were collected from the patients on the day just before the chemotherapy, the 7(th) day, and the 21(st) (if 21 days per cycle of the chemotherapy) or 28(th) day of treatment. Concentration of malondialdehyde (MDA), activity of glutathione peroxidase (GSH-Px), and total superoxide dismutase (T-SOD) of serum samples were analyzed biochemically. RESULTS:(1)Administration of chemotherapy significantly increased serum MDA level on the 7(th) day compared with that before chemotherapy (mean+/-SD,6.12+/-1.94 micromol/L versus 4.63+/-1.87 micromol/L,P< 0.01). The increased serum MDA level was restored partially (5.05+/-2.07)micromol/L on the 21(th) or 28(th) day, but still higher than that before chemotherapy (P< 0.05). (2)Serum activity of T-SOD and GSH-Px decreased on the 7(th) day (P< 0.01) and restored partially on the 21(th) or 28th day, but still lower than that before chemotherapy (T-SOD, P< 0.05;GSH-Px,P< 0.01).(3)Co-treatment of GSH prevents lipid peroxidation and depletion of antioxidant enzymes by chemotherapy partially but significantly (P< 0.01). (4)Similar results were obtained in both AB group and BA group. CONCLUSION: Chemotherapy depletes antioxidant capability of cancer patients and co- treatment of GSH might prevent such depletion.