Ketoisocaproate infusion improves survival from experimental sepsis by an antioxidant mechanism.

Circulatory shock Pub Date : 1993-12-01
T Yonekura, S Matsusue, M Walser
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Abstract

Sepsis was induced in rats by cecal ligation and puncture. A nutrient mixture was infused that also contained either (A) sodium 2-ketoisocaproate (NaKIC) or (B) NaHCO3, at 18.75 mmol kg/day. In group A, 34 of 43 rats (79%) survived, while only 24 of 44 rats (55%) in group B survived (P < 0.02). In a second experiment, cecal ligation and puncture were performed 1 week after bilateral adrenalectomy or sham adrenalectomy. All adrenalectomized rats died within 2 days of CLP, whether corticosterone replacement level was low, normal, or high. Four of eight sham-adrenalectomized rats receiving NaHCO3 died, but none of seven receiving NaKIC died. Combining both experiments by ANOVA, the effect of KIC on survival in adrenal-intact animals is highly significant (P = 0.002). In NaKIC-infused rats, blood level of pyruvate was higher on day 5 (P < 0.01), and plasma as well as blood levels of oxidized glutathione and ratio of oxidized/reduced glutathione were significantly lower. We conclude that KIC infusion improves survival of septic rats by an antioxidant mechanism, probably involving reaction with hydrogen peroxide.

酮异己酸输注通过抗氧化机制提高实验性败血症的生存率。
用盲肠结扎法和穿刺法诱导大鼠脓毒症。同时注入含有(A) 2-酮异己酸钠(NaKIC)或(B) NaHCO3的营养混合物,剂量为18.75 mmol kg/d。A组43只大鼠中有34只(79%)存活,B组44只大鼠中只有24只(55%)存活(P < 0.02)。在第二个实验中,在双侧肾上腺切除术或假肾上腺切除术后1周进行盲肠结扎和穿刺。无论皮质酮替代水平低、正常或高,所有肾上腺切除大鼠均在CLP后2天内死亡。接受NaHCO3治疗的8只假肾上腺切除大鼠中有4只死亡,但接受NaKIC治疗的7只没有死亡。经方差分析,KIC对肾上腺未损伤大鼠的存活率有显著影响(P = 0.002)。注射nakic的大鼠第5天血中丙酮酸水平升高(P < 0.01),血浆和血中氧化谷胱甘肽水平及氧化/还原性谷胱甘肽比值显著降低。我们得出结论,KIC输注通过抗氧化机制提高脓毒症大鼠的存活率,可能涉及与过氧化氢的反应。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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