塩化水銀誘導性ラット腎障害モデルを用いたストレス耐性獲得機序に関する研究 : ACTHによる細胞内グルタチオン増加の役割

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The cellular defense systems protect the living body against stress exposure and raise its resistance to harmful stress. The cellular mechanism of this stress-induced resistance, however, remains unknown. The present study was conducted to clarify this mechanism. We found that laparotomy, conducted two days before the subcutaneous administration of HgCl_2, reduced the extent of HgCl_2-induced acute renal tubular necrosis (oxidative stress). Glutathione (GSH), the most abundant and ubiquitous cellular antioxidant, was found to have increased in the kidneys, but not in the adrenals or liver of rats two days after laparotomy. This finding suggests that laparotomy-induced elevation of GSH content raises resistance against oxidative stress. LLC-PK1 cells, i.e., porcine renal tubule-derived cells, were cultured with butionine salfoximine (BSO), a γ-glutamylcysteine synthetase inhibitor, and cellular GSH contents were reduced. Cells were then exposed to HgCl_2. LDH leakage in the medium increased significantly in BSO-pretreated cells, but not in nontreated cells. This in vitro finding confirmed the protective role of GSH against oxidative stress. We then examined the possible participation of the pituitary-adrenal axis in the laparotomy-induced increase in renal GSH. Laparotomy stress activates the pituitary-adrenal axis as is evidenced by the fact that rats undergoing laparotomy had significantly heavier adrenals than those not undergoing it. Two days' administration of ACTH increased renal and adrenal GSH contents significantly in a dose-dependent manner, but not hepatic content. Pretreatment with ACTH also prevented HgCl_2-induced renal damage. In conclusion, we demonstrated that laparotomy-induced resistance to oxidative stress may be mediated by the activation of the pituitary-adrenal axis and the elevation of renal GSH contents.
1997-02-25

塩化水銀誘導性ラット腎障害モデルを用いたストレス耐性獲得機序に関する研究 : ACTHによる細胞内グルタチオン増加の役割

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