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首页> 外文期刊>The Journal of toxicological sciences >Evaluation of hepatic damage by reactive metabolites - Administration with consideration of circadian variation of murine hepatic glutathione levels
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Evaluation of hepatic damage by reactive metabolites - Administration with consideration of circadian variation of murine hepatic glutathione levels

机译：反应性代谢物对肝损害的评估-考虑鼠肝谷胱甘肽水平的昼夜变化而给药

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Generally, reactive metabolites are detoxified by conjugation with glutathione (GSH). A GSH-depleted model was prepared by administering L-buthionine-(S,R)-sulfoximine (BSO), which can be used to detect hepatic damage by reactive metabolites. However, BSO may cause adverse effects on other organs, such as renal damage by reactive metabolites because it depletes GSH in the whole body. The present study was designed to examine whether it was possible to specifically detect hepatic damage by reactive metabolites without reducing renal GSH levels by administering BSO in a time course when hepatic GSH levels are naturally reduced. Male BALB/c mice were administered reverse osmosis (RO) water or 20 mmol/l BSO in drinking water for 4 days. Subsequently, animals in the RO water group were orally administered 500 mg/kg acetaminophen (APAP) at 9:00 or 15:00 and in the BSO group at 9:00 for 4 days. As a result, severe hepatic damage and necrosis of the renal proximal tubules were observed in the BSO/APAP administration at 9:00 group, and all animals died on 1 or 2 days after APAP administration. Hepatic damage was clearly increased in the RO water/APAP administration at 15:00 group compared with the RO water/APAP administration at 9:00 group. However, renal damage and deaths were not observed. This BSO administration model may detect renal damage induced by reactive metabolites. Using an administration time course, whereby hepatic GSH levels were naturally reduced, hepatic damage by reactive metabolites can be detected without secondary renal effects.
机译：通常，反应性代谢产物通过与谷胱甘肽（GSH）结合而被解毒。通过施用L-丁硫氨酸-（S，R）-亚磺酰亚胺（BSO）制备了GSH耗竭模型，该模型可用于检测反应性代谢产物对肝的损害。但是，BSO可能会消耗全身的GSH，因此可能会对其他器官造成不良影响，例如反应性代谢产物对肾脏的损害。本研究旨在检查是否有可能通过在自然降低肝GSH水平的时间内施用BSO来通过反应性代谢物特异性检测肝损害而不会降低肾GSH水平。给雄性BALB / c小鼠饮用饮用水中的反渗透（RO）水或20 mmol / l BSO，持续4天。随后，在RO水组的动物在9:00或15:00口服500 mg / kg对乙酰氨基酚（APAP），在BSO组的动物在9:00口服4天。结果，在9:00组的BSO / APAP给药中观察到严重的肝损伤和肾近端小管坏死，并且在APAP给药后1或2天所有动物死亡。与在9:00组进行RO水/ APAP给药相比，在15:00组进行RO水/ APAP给药对肝损害明显增加。但是，未观察到肾脏损害和死亡。该BSO给药模型可以检测由反应性代谢物引起的肾脏损害。使用给药时程，自然降低肝GSH水平，可以检测到反应性代谢产物对肝的损害，而没有继发性肾脏影响。

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