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过量摄入抗坏血酸对大鼠肝脏和肝外I相及II相药物代谢的影响

Effect of excessive intake of ascorbic acid on hepatic and extra-hepatic phase I and phase II drug metabolism in rat.

作者信息

Khanduja K L, Gupta M P, Koul A, Koul I B, Sharma R R

出版信息

Biochem Int. 1987 Jan;14(1):135-44.

PMID:3566772
Abstract

Guinea pig is the animal model of choice for studies on effects of ascorbic acid (AA). However, rat is one of the largely used animals for investigations related to chemical carcinogenesis. Therefore, the present study was designed to evaluate the changes induced by high intake of the vitamin in xenobiotic and carcinogen metabolizing status of the organs. Male Wistar rats, dosed daily with 50 mg AA/100 g body weight for 10 weeks, demonstrated a small non-significant increase in hepatic, pulmonary and colon cytochrome P-450 (Cyt. P-450) contents, which was accompanied with a significant increase in hepatic and pulmonary arylhydrocarbon hydroxylase (AHH) activities. Phase II enzymes of drug metabolism responded in different ways to increased intake of AA. UDP-glucuronyltransferase (UDPGT) activity was unaffected in liver and colon, but it was increased (p less than 0.005) in lung. Activities of glutathione S-transferase (GST) were decreased in the three organs. Inducibility of AHH by 3-methylcholanthrene (MCA) or phenobarbital (PB) was largely reduced due to AA feeding. Besides this, MCA and PB had differential effects on enzymatic levels in AA fed rats. When compared with our earlier observations in guinea pig, it was found that rat responded similarly to guinea pig to increased intake of AA with regard to hepatic AHH, Cyt. P-450, UDPGT and GST, pulmonary AHH, Cyt. P-450 and Cyt. b5, and all studied colon enzymes, except GST.

摘要

豚鼠是研究抗坏血酸(AA)作用的首选动物模型。然而,大鼠是化学致癌研究中广泛使用的动物之一。因此,本研究旨在评估高剂量摄入该维生素对器官中异生物质和致癌物代谢状态所诱导的变化。雄性Wistar大鼠,每天按50mg AA/100g体重给药10周,肝脏、肺和结肠细胞色素P-450(Cyt. P-450)含量有小幅但无显著意义的增加,同时肝脏和肺芳烃羟化酶(AHH)活性显著增加。药物代谢的Ⅱ相酶对AA摄入量增加的反应各不相同。尿苷二磷酸葡萄糖醛酸转移酶(UDPGT)活性在肝脏和结肠中未受影响,但在肺中增加(p<0.005)。谷胱甘肽S-转移酶(GST)活性在三个器官中均降低。由于喂食AA,3-甲基胆蒽(MCA)或苯巴比妥(PB)对AHH的诱导能力大幅降低。除此之外,MCA和PB对喂食AA大鼠的酶水平有不同影响。与我们早期在豚鼠中的观察结果相比,发现大鼠在肝脏AHH、Cyt. P-450、UDPGT和GST、肺AHH、Cyt. P-450和Cyt. b5以及所有研究的结肠酶(除GST外)方面,对AA摄入量增加的反应与豚鼠相似。

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Biochem Int. 1987 Jan;14(1):135-44.
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