LaLonde C, Nayak U, Hennigan J, Demling R H
Brigham & Women's Hospital, Boston, Massachusetts 02115, USA.
J Burn Care Rehabil. 1997 May-Jun;18(3):187-92. doi: 10.1097/00004630-199705000-00002.
We studied the effect of the oral administration of a water-soluble antioxidant solution containing ascorbic acid, glutathione, and a precursor for glutathione synthesis, N-Acetyl-L-cysteine, on liver antioxidant activity, liver cell energetics, and mortality in rats in response to a 20% third-degree burn injury challenged 5 days later with an intraperitoneal injection of 30 mg/kg endotoxin. Rats with burns were fluid-resuscitated with subcutaneous Ringer's lactate solution according to the Parkland formula (4 cc/kg/%burn). Rats challenged with endotoxin 5 days after burn were given an additional 100 ml/kg of subcutaneous Ringer's lactate solution immediately after the injection of endotoxin. A group of rats with burns challenged with endotoxin 5 days after burn were given an oral antioxidant solution beginning after burn injury. Liver cell energetics were measured as tissue energy charge potential (ECP), adenosine triphosphate (ATP) content, and total adenine nucleotides. The levels of endogenous liver glutathione, catalase, vitamin C, and vitamin E were measured to monitor antioxidant status. We found that burn injury alone did not produce any mortality over the 6-day period despite a 35% decrease in liver energy charge potential resulting from a decrease in ATP, a 34% decrease in liver catalase activity, and a 20% decrease in liver vitamin C. It was interesting that glutathione increased and vitamin E remained unchanged. We found that endotoxin injury combined with burn injury produced a 61% mortality rate with a 63% decrease in liver energy charge potential, again resulting from a decrease in ATP, a 74% decrease in liver catalase activity, a 16% decrease in vitamin C, and a 29% decrease in vitamin E. Glutathione was significantly decreased compared with burn alone. We compared the liver antioxidant status of survivors with that of nonsurvivors who were killed when appearing moribund and found that glutathione was decreased by 51% and vitamin C by 73% in nonsurvivors over that in survivors, whereas catalase and vitamin E levels were comparable between the two groups. The oral administration of the antioxidants prevented mortality and the decrease in antioxidant activity and attenuated the decrease in energy charge potential. We conclude that a 20% burn produces a modest decrease in liver energy charge potential and antioxidant defenses without producing mortality. The addition of endotoxin further decreases liver antioxidant defenses, liver energy charge potential, and markedly increases mortality. Antioxidants, given post-burn, restored antioxidant defenses, attenuated the altered cell energetics, and prevented mortality, indicating oxidants to be the cause of mortality. This data also suggests that a critical value of decreases in antioxidant defenses and ATP exists, resulting in mortality.
我们研究了口服一种含有抗坏血酸、谷胱甘肽以及谷胱甘肽合成前体N - 乙酰 - L - 半胱氨酸的水溶性抗氧化剂溶液，对大鼠肝脏抗氧化活性、肝细胞能量代谢及死亡率的影响。这些大鼠先遭受20%的三度烧伤，5天后腹腔注射30mg/kg内毒素进行刺激。烧伤大鼠按照帕克兰公式（4cc/kg/%烧伤面积）用皮下乳酸林格氏液进行液体复苏。烧伤后5天接受内毒素刺激的大鼠在注射内毒素后立即额外给予100ml/kg皮下乳酸林格氏液。一组烧伤后5天接受内毒素刺激的大鼠在烧伤后开始口服抗氧化剂溶液。肝细胞能量代谢通过组织能荷电位（ECP）、三磷酸腺苷（ATP）含量及总腺嘌呤核苷酸来测定。测定肝脏内源性谷胱甘肽、过氧化氢酶、维生素C和维生素E的水平以监测抗氧化状态。我们发现，仅烧伤在6天内未导致任何死亡，尽管由于ATP减少肝脏能荷电位下降35%，肝脏过氧化氢酶活性下降34%，肝脏维生素C下降20%。有趣的是，谷胱甘肽增加而维生素E保持不变。我们发现内毒素损伤与烧伤联合导致死亡率为61%，肝脏能荷电位下降63%，同样是由于ATP减少，肝脏过氧化氢酶活性下降74%，维生素C下降16%，维生素E下降29%。与单纯烧伤相比，谷胱甘肽显著降低。我们比较了存活大鼠与濒死时处死的非存活大鼠的肝脏抗氧化状态，发现非存活大鼠的谷胱甘肽比存活大鼠降低51%，维生素C降低73%，而两组之间过氧化氢酶和维生素E水平相当。口服抗氧化剂可预防死亡及抗氧化活性的降低，并减轻能荷电位的下降。我们得出结论，20%的烧伤会使肝脏能荷电位和抗氧化防御适度降低，但不会导致死亡。内毒素的加入进一步降低肝脏抗氧化防御、肝脏能荷电位，并显著增加死亡率。烧伤后给予抗氧化剂可恢复抗氧化防御，减轻细胞能量代谢改变，并预防死亡，表明氧化剂是死亡的原因。该数据还表明，抗氧化防御和ATP的降低存在一个临界值，会导致死亡。
