Hintz S R, Kim C B, Vreman H J, Stevenson D K
Department of Pediatrics, Stanford University School of Medicine, California 94305.
Pediatr Res. 1988 Jan;23(1):50-3. doi: 10.1203/00006450-198801000-00011.
We assessed the in vivo and in vitro effects of antibiotics and tin-protoporphyrin (TP) on intestinal heme oxygenase (HO) activity using a gas chromatographic assay. This method measures the carbon monoxide produced from heme in the presence of NADPH. After in vivo administration of kanamycin (10 mg/kg body weight), ampicillin (200 mg/kg body weight) or neomycin (60 mg/kg body weight) with or without TP (65 mumol/kg body weight) to suckling rats, no significant difference in HO activity along the small intestine was observed. In vitro exposure of adult rat intestinal preparations to the antibiotics showed no significant decrease in HO activity between control and experimental tissue preparations. A concentration-dependent stimulatory effect of neomycin was observed. Subcutaneous administration of TP (25 mumol/kg body weight) to adult male Wistar rats revealed no significant inhibition of the intestine. However, in vitro addition of TP (12.5 microM) to the control tissue preparations of adult Wistar rats revealed highly significant inhibition in liver and spleen when compared to the unexposed control tissues. In contrast, when TP was added to control intestinal preparations no inhibition was observed. These findings suggest that suckling rat intestinal heme oxygenase is not inhibited by in vivo treatment with high concentrations of kanamycin, ampicillin, or neomycin. Furthermore, these antibiotics are not in vitro inhibitors of adult rat intestinal HO. Finally, adult rat intestinal HO is not inhibited either in vivo or in vitro by a concentration of TP that significantly inhibits liver and spleen activity.
我们使用气相色谱分析法评估了抗生素和锡原卟啉（TP）对肠道血红素加氧酶（HO）活性的体内和体外作用。该方法测量在烟酰胺腺嘌呤二核苷酸磷酸（NADPH）存在下血红素产生的一氧化碳。对乳鼠体内给予卡那霉素（10毫克/千克体重）、氨苄青霉素（200毫克/千克体重）或新霉素（60毫克/千克体重），无论是否同时给予TP（65微摩尔/千克体重），沿小肠的HO活性均未观察到显著差异。成年大鼠肠道制剂在体外暴露于抗生素后，对照组织制剂和实验组织制剂之间的HO活性没有显著降低。观察到新霉素有浓度依赖性刺激作用。对成年雄性Wistar大鼠皮下给予TP（25微摩尔/千克体重），未发现对肠道有显著抑制作用。然而，与未暴露的对照组织相比，在成年Wistar大鼠的对照组织制剂中体外添加TP（12.5微摩尔）后，肝脏和脾脏出现了高度显著的抑制。相反，当向对照肠道制剂中添加TP时，未观察到抑制作用。这些发现表明，高浓度的卡那霉素、氨苄青霉素或新霉素体内治疗不会抑制乳鼠肠道血红素加氧酶。此外，这些抗生素不是成年大鼠肠道HO的体外抑制剂。最后，显著抑制肝脏和脾脏活性的TP浓度在体内或体外均不会抑制成年大鼠肠道HO。
