이트라코나졸 전처치가 내독소로 유도된 백서의 급성 폐손상에 미치는 영향
The Effect of Itraconazole Pretreatment in Lipopolysaccharide-Induced Acute Lung Injury in Rats
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Background: Despite the fact that a randomized controlled trial did not support the use of ketoconazole for treatment of acute lung injury (ALI), there is evidence that pretreatment with ketoconazole might prevent ALI in critically ill patients. An in vitro study showed, however, that itraconazole was a more potent inhibitor of thromboxane and leukotriene formation than was ketoconazole. We investigated the effect of itraconazole pretreatment in lipopolysaccharide (LPS)-induced ALI in rats. Methods: Twenty-one pathogen free, male Sprague-Dawley rats were administered either saline or LPS (5 mg/kg of body weight) intratracheally, with or without intraperitoneal pretreatment of itraconazole (2.5 mg/kg). Six hours after saline or LPS treatment (7 h after itraconazole pretreatment), samples were obtained. Results: Compared with the saline group, LPS group had increased total cell count, polymorphonuclear leukocyte differential count, protein, lactate dehydrogenase (LDH) and cytokines in BAL fluid. Itraconazole pretreatment decreased polymrphonuclear leukocyte differential count, protein and LDH in BAL fluid compared with those of LPS-treated rats without itraconazole pretreatment. Itraconazole pretreatment also decreased the elevated BAL fluid levels of interleukin-1β (IL-1β) and cytokine-induced neutrophil chemoattractant (CINC) by LPS. There was, however,no difference in the BAL fluid tumor necrosis factor α (TNF-α) level in terms of itraconazole pretreatment in LPS-treated rats. Histopathologic features of LPS-induced ALI were attenuated by itraconazole pretreatment. Conclusions: These results suggest that itraconazole pretreatment attenuated LPS-induced ALI in rats. Decreases in levels of IL-1β and CINC would likely be associated with attenuation of LPS-induced ALI in rats by itraconazole pretreatment.
Abstract
Background: Despite the fact that a randomized controlled trial did not support the use of ketoconazole for treatment of acute lung injury (ALI), there is evidence that pretreatment with ketoconazole might prevent ALI in critically ill patients. An in vitro study showed, however, that itraconazole was a more potent inhibitor of thromboxane and leukotriene formation than was ketoconazole. We investigated the effect of itraconazole pretreatment in lipopolysaccharide (LPS)-induced ALI in rats. Methods: Twenty-one pathogen free, male Sprague-Dawley rats were administered either saline or LPS (5 mg/kg of body weight) intratracheally, with or without intraperitoneal pretreatment of itraconazole (2.5 mg/kg). Six hours after saline or LPS treatment (7 h after itraconazole pretreatment), samples were obtained. Results: Compared with the saline group, LPS group had increased total cell count, polymorphonuclear leukocyte differential count, protein, lactate dehydrogenase (LDH) and cytokines in BAL fluid. Itraconazole pretreatment decreased polymrphonuclear leukocyte differential count, protein and LDH in BAL fluid compared with those of LPS-treated rats without itraconazole pretreatment. Itraconazole pretreatment also decreased the elevated BAL fluid levels of interleukin-1β (IL-1β) and cytokine-induced neutrophil chemoattractant (CINC) by LPS. There was, however,no difference in the BAL fluid tumor necrosis factor α (TNF-α) level in terms of itraconazole pretreatment in LPS-treated rats. Histopathologic features of LPS-induced ALI were attenuated by itraconazole pretreatment. Conclusions: These results suggest that itraconazole pretreatment attenuated LPS-induced ALI in rats. Decreases in levels of IL-1β and CINC would likely be associated with attenuation of LPS-induced ALI in rats by itraconazole pretreatment.
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