敗血症是1999及2000年台灣地區第14大死因，其發生率在1980年代增加了139%，死亡率也逐年上升，葛蘭氏陰性菌是常見的敗血症病原體，位在它細胞外壁上的脂多醣能誘發宿主產生發炎反應及氧化性壓力，嚴重時會引發敗血症，進而造成多重器官衰竭、甚至死亡；研究發現芝麻油具有良好的抗發炎及抗氧化效果，能清除自由基、減少脂質過氧化、改善脂多醣引起的多重器官衰竭、並提高實驗動物敗血症存活率。
本研究探討芝麻油對低劑量脂多醣體誘發輕微內毒素血症24小時內的影響；先以腹腔注射每公斤體重1毫克的脂多醣，誘使實驗動物大白鼠產生輕微的內毒素血症，隨即灌食每公斤體重8毫升的芝麻油，然後在注射脂多醣後第1、3、6、12或24小時抽血，分析血中促發炎細胞激素腫瘤壞死因子a及介白素1b、抗發炎細胞激素介白素10、一氧化氮、超氧自由基的含量，酵素性抗氧化防禦的超氧化物岐化酶及過氧化氫酶活性，非酵素性抗氧化防禦的麩氨基硫、脂質過氧化、天冬胺酸轉化酶、精胺酸轉化酶、鹼性磷酸酶及總膽紅素的量做為肝細胞受傷的指標。
研究結果顯示芝麻油對輕微內毒素血症的影響如下：(1) 明顯增加第1小時的腫瘤壞死因子a，抑制第3小時的腫瘤壞死因子a；(2) 抑制第3小時的介白素1b、增加第12小時的介白素1b；(3) 有抑制介白素10的趨勢；(4) 明顯增加第1、3、6及12小時的一氧化氮；(5) 減少第12及24小時的超氧自由基；(6) 對超氧化物岐化酶及過氧化氫酶活性影響不大；(7) 明顯增加第1、12及24小時的麩氨基硫；(8) 稍微增加脂多醣誘發的脂質過氧化；(9) 加重脂多醣誘發的肝細胞受損。由此推測，大量的芝麻油不但無法改善輕微內毒素血症，還會惡化病情。

Lipopolysaccharide (LPS), the main component of the outer cell wall in all Gram-negative bacteria, triggers severe pathologic alternations, such as systemic inflammation, multiple organ dysfunction (MOD), and death in clinical studies. Despite significant advances in the management of sepsis, MOD remains the leading cause of death in septic patients. It was found that sesame oil (SO) could scavenge free radical, reduce lipid peroxidation (LPO), attenuate the LPS-induced MOD, and increase survival rate of sepsis in animal studies.
Rats were challenged intraperitoneally with 1 mg/kg LPS. SO (8 ml/kg) was given right after LPS administration. Blood samples were collected at 1, 3, 6, 12, or 24 hrs after LPS-injection. Serum levels of asparate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALKP), total bilirubin (TBIL), LPO, superoxide anion, the activities of superoxide dismutase (SOD) and catalse (CAT), serum levels of glutathione (GSH), nitric oxide, pro-inflammatory cytokines tumor necrosis factor-alpha (TNF-a) and interleukin-1 beta (IL-1b), and anti-inflammatory cytokine interleukin-10 (IL-10) were determined.
After LPS injection, SO: (1) up-regulated LPS-induced TNF-a at 1 hr and down-regulated at 3 hrs; (2) reduced IL-1β at 3 hrs, but increased at 12 hrs; (3) slightly but not significantly inhibited IL-10 levels; (4) increased serum levels of nitric oxide at 1, 3, 6, and 12 hrs; (5) reduced LPS-induced superoxide anion at 12 and 24 hrs; (6) failed to affect SOD and CAT activities; (7) up-regulated GSH at 1, 12 and 24 hrs; (8) slightly but not significantly increased LPS-induced LPO; (9) increased LPS-induced liver injury. It is concluded that SO may not protect against low-dose LPS-induced endotoxemia in rats.

Abraham E, Wunderink R, Silerman H, Perl TM, Nasraway S, Levy H, Bone R, Wenzel RP, Balk R, Allred R, Pennington JE, Wherry JC. Efficacy and safety of monoclonal antibody to human tumor necrosis factor-a in patients with sepsis syndrome: a randomized, controled, double-blind, multicenter clinical trial. JAMA 273: 934-41, 1995.
Akimoto K, Kitagawa Y, Akamatsu T, Hirose N, Sugano M, Shimizu S, Yamada H. Protective effect of sesamin against liver damage caused by alcohol or carbon tetrachloride in rodents. Ann Nutr Metab 37: 218-224, 1993.
Balk RA. Severe sepsis and septic shock: Difinitions, epidemiology and clinical manifestations. Crit Care Clin 16: 179-192, 2000.
Ben-Shaul V, Lomnitski L, Nyska A, Zurovsky Y, Bergman M, Grossman S. The effect of natural antioxidants, NAO and apocynin, on oxidative stress in the rat heart following LPS challenge. Toxicol let 123: 1-10, 2001.
Blackwell TS, Christman JW. Sepsis and cytokines: current status. Br J Anaesth 77: 110-117, 1996.
Bone RC, Fisher CJ, Clemmer TP, Slotman GJ, Metz CA, Balk RA. A controled clinical trial of high does methylprednisolone in the treatment of severe sepsis and septic shock. N Engl J Med 317: 653-658, 1987.
Bone RC, Grodzin CJ, Balk RA. Sepsis: A new hypothesis for pathogenesis of the disease process. Chest 112: 235-243, 1997.

Bone RC. Gram-negative sepsis: Background, clinical features, and intervention. Chest 100: 802-808, 1991.
Boughton-Smith NK, Evans SM, Laszlo F, Whittle BJR, Moncada S. The induction of nitric oxide synthase and intestinal vascular permeability by endotoxin in the rat. Br J Pharmacol 110: 1189-1195, 1993.
Cadenas S, Cadenas AM. Fighting the stranger: antioxidant protection against endotoxin toxicity. Toxicology 180: 45-63, 2002.
Callahan LA, She ZW, Nosek TM. Superoxide, hydroxyl radical, and hydrogen peroxide effects on single-diaphragm fiber contractile apparatus. J Appl Physiol 90: 45-54, 2001.
Casey LC. Immunologic response to infection and its role in septic shock. Crit Care Clin 16: 193-213, 2000.
Cerwinka WH, Cooper D, Krieglstein CF, Ross CR, McCord JM, Granger DN. Superoxide mediates endotoxin-induced platelet-endothelial cell adhesion in intestinal venules. Am J Physiol 284: H535-541, 2003.
Chavali SR, Utsunomiya T, Forse RA. Increased survival after cecal ligation and puncture in mice consuming diets enriched with sesame seed oil. Crit Care Med 29: 140-143, 2001.
Chavali SR, Zhong WW, Utsumomiya T, Forse RA. Decreased production of interleukin-1-beta, prostaglandin-E2 and thromboxane-B2, and Elevated levels of interleukin-6 and -10 are associated with increased survival during endotoxic shock in mice consuming diets enriched with sesame oil supplemented with Quil-A saponin. Int Arch Allergy Immunol 114:153-160, 1997.

Demling R, Lalonde C, Ikegami k, Picard L, Nayak U. Alpha-tocopherol attenuates lung edema and lipid peroxidation caused by acute zymosan-induced peritonotos. Surgery 117: 226-231, 1995.
Eieserich JP, Patel RP, O'Donnell VB. Pathophysiology of nitiric oxide and related sepcies: free radical reactions and modification of biomolecules. Mol Aspects Med 19: 221-357, 1998.
Faggioni R, Gatti S, Demitri MT, Delgado R, Echtenacher B, Gnocchi P, Heremans H, Ghezzi P. Role of xanthine oxidase and reactive oxygen intermediates in LPS- and TNF-induced pulmonary edema. J Lab Clin Med 123: 394-399, 1994.
Feihl F, Waeber B, Liaudet L. Is nitric oxide overproduction the target of choice for the management of septic shock? Pharmacol Ther 91: 179-213, 2001.
Fisher CJ, Dhainaut JF, Opal SM, Pribble JP, Balk RA, Slotman GJ, Iberti TJ, Rackow EC, Shapiro MJ, Greenman RL. Recombinant human interleukin-1 receptor antagonist in the treatment of patients with sepsis syndrome. Results from a randomized, double-blind, placebo-controlled trial. Phase III rhIL-1ra Sepsis syndrome Study Group. JAMA 271: 1836-1843, 1994a.
Fisher CJ, Slotman GJ, Opal SM et al. Initial evaluation of human recombinant interleukin-1 receptor antagonist in the treatment of sepsis syndrome: a randomized, open-label, placebo-controlled multicenter trial. Crit Care Med 22: 12-21, 1994b.
Goode HF, Cowley HC, Walker BE, Howdle PD, Webster NR. Decreased antioxidant state and increased lipid peroxidation in patients with septic shock and secondary organ dysfunction. Crit Care Med 23: 646-651, 1995.
Gaetani GF, Galiano S, Canepa L, Ferraris AM, Kirkman HN. Catalase and glutathionee peroxidase are equally active in detoxification of hydrogen peroxide in human erythrocytes. Blood 73: 334-9, 1989.
Halliwell B, Gutteridge JMC (Eds): Free radicals in biology and medicine. Clarendon Press, Oxford p86-187, 1989.
He P, Noda Y, Sugiyama K. Green tea suppresses lipopolysaccharide-induced liver injury in D-Galactosamine-sensitized rats. J Nutr 131: 1560-1567, 2001.
Hinshaw LB. Sepsis / septic shock: An abbreviated review. Crit Care Med 24: 1072-1078, 1996.
Hirose N, Doi F, Ueki T, Akazawa K, Chijiiwa K, Sugano M, Akimoto K, Shimizu S, Yamada H. Suppressive effect of sesamin against 7,12-dimethl-benz[a]-anthracene induced at mammary carcinogenesis. Anticancer Res 12: 1259-1266, 1992.
Hirose N, Inove T, Nishihara K, Sugano M, Akimoto K, Shimizu S, Yamada H. Inhibition of cholesterol absorption and synthesis in rats by sesamin. J Lipid Res 32: 629-639, 1991.
Hon WM, Lee KH, Khoo HE. Nitric oxide in liver disease: friend, foe or just passerby? Ann N Y Acad Sci 962: 275-295, 2002.
Hsu DZ, Liu MY. Sesame oil attenuates multiple organ failure and increases survival rate during endotoxemia in rats. Crit Care Med 30: 1859-1862, 2002.
Increased in national hospital discharge survey rates for septicemia-United States. 1979-1987. Morbid Mortal Weekly Rep 39: 31-34, 1990.
Kang MH, Naito M, Sakai K, Uchida K, Osawa T. Mode of action of sesame lignans in protection low-density lipoprotein against oxidative damage in vitro. Life Sci 66: 161-171, 2000.
Kheir-Eldin AA, Motawi TK, Gad MZ, Abd-ElGawad HM. Protective effect of vitamin E, b-carotene and N-acetylcysteine from the brain oxidative stress induced in rats by lipopolysaccharide. Int J Biochem Cell Biol 33: 475-482, 2001.
Kim YM, Talanian RV, Li J, Billiar TR. Nitric oxide prevents IL-1b and IFN-g-induced factor (IL-18) releasing from macrophage by inhibiting caspase-1 (IL-1b-converting enzyme). J Immunol 161: 4122-4128, 1998.
Kita S, Matsumura Y, Morimoto S, Akimoto K, Fruya M, Oka N, Tanaka T. Antihypertensive effect of sesamin II: protection against two-kidney, one clip renal hypertension and cardiovascular hypertrophy. Biol Pharm Bull 18: 1283-1285, 1995.
Klebanoff SJ, Vadas MA, Harlan JM, Sparks LH, Gamble JR, Agosti JM, Waltersdorph AM. Stimulation of neutrophils by tumor necrosis factor. J Immunol 136: 4220-4225, 1986.
Kreger BE, Craven DE, McCabe WR. Gram-negative bacteremia. IV. Re-evaluation of clinical features and treatment in 612 patients. Am J Med 68: 344-355, 1980.
László F, Whittle BJR, Evans SM, Moncada S. Association of microvascular leakage with induction of nitric oxide synthase: effect of nitric oxide synthase inhibitors in various organs. Eur J Pharmacol 283: 47-53, 1995.
Levy MM, Fink MP, Marshall JC, Abraham E, Angus D, Cook D, Cohen J, Opal SM, Vincent JL, Graham Ramsay for the international sepsis definitions conference. 2001/SCCM/ESICM/ACCP/ATS/SIS international sepsis definitions conference. Intensive Care Med 29: 530-538, 2003.
Manhart N, Oismuller C, Lassning A, Spittler A, Sautner T, Gotzinger P, Fugger R, Roth E. Receptor and non-receptor mediated formation of superoxide anion and hydrogen peroxide in neutrophils of intensive care patients. Wien Klin Wochenschr 110: 796-801, 1998.
Miles AM, Bohle DS, Glassbrenner PA, Hansert B, Wink DA, Grisham MB. Modulation of superoxide-dependent oxidation and hydroxylation reactions by nitric oxide. J Biol Chem 271: 40-47, 1996.
Minamiya Y, Abo S, Kitamura M, Izumi K, Kimura Y, Tozawa K, Saito S. Endotoxin-induced hydrogen peroxide production in intact pulmonary circulation of rat. Am J Respir Crit Care Med 52: 348-354, 1995.
Miura T, Muraoka S, Fujimoto Y. Lipid peroxidation inducede by phenylbutazone radicals. Life Sci 70: 2611-2621, 2002.
Miyahara Y, Hibasami H, Katsuzaki H, Imai K, Osawa T, Ina K, Komiya T. Sesaminol from sesame seed induced apoptosis in human lumphoid oeukemia Molt 4B cells. Int J Mol Med 7: 485-488, 2001.
Oberholzer A, Oberholzer C, Moldawer LL. Interleukin-10: A complex role in the pathogenesis of sepsis syndromes and its potential as an anti-inflammatory drug. Crit Care Med 30 (suppl): S58-S63, 2002.
Poll TVD, Büller HR, Cate HT, Wortel CH, Bauer KA, Deventer SJHV, Hack CE, Sauerwein HP, Rosenberg RD, Cate JWT. Activation on coagulation after administration of tumor necrosis factor to normal subjects. N Engl J Med 322: 1622-1627, 1990.

Rangel-Frausto MS, Pittet D, Costigan M, Hwang T, Davis RS, Wenzel RP. The natural history of the systemic inflammatory response syndrome (SIRS). JAMA 273: 117-123, 1995.
Schmidt H, Weigand MA, Li C, Schmidt W, Martin E, Bardenheuer HJ. Intestinal formation of hypoxanthine and uric acid during endotoxemia. J Surg Res 71: 61-66, 1997.
Shimizu S, Akimoto K, Shinmen Y, Kawashima H, Sugano M, Yamada H. Sesamin is a potent and specific inhibitor of △-5 desaturase in polyunsaturated fatty acid biosynthesis. Lipids 26: 512-516, 1991.
Simon JE, Chadwick AF, Craker LE. Herbs: An indexed bibliography 1971-1980. The scientific literature on selected herbs, and aromatic and medicinal plants of the temperate zone. Hamden: Archon Books, 1984 (http://www.hort. purdue.edu/newcrop/med-aro/factsheets/SESAME.html).
Spolarics Z, Wu JX. Role of glutathionee and calalase in H2O2 detoxification in LPS-activated hepatic endothelial and kupffer cells. Am J Physiol 273: G1304-1311, 1997.
Takeyama N, Shoji Y, Ohashi K, Tanaka T. Role of reactive oxygen intermediates in lipopolysaccharide-mediated hepatic injury in the rat. J Surg Res 60: 258-262, 1996.
Taylor DE, Ghio AJ, Piantadosi CA. Reactive oxygen species produced by liver mitochondria of rats in sepsis. Arch Biochem Biophys 316: 70-76, 1995.
The Veterans administration systemic sepsis cooperative study group. Effect of high-does glucocorticoid therapy on mortality in patients with clinical signs of systemic sepsis. N Engl J Med 317: 659-665, 1987.
Vincent JL. New therapies in sepsis. Chest 112: 330S-338S, 1997.
Wink DA, Mitchell JB. Chemical biology of nitric oxide: insight into regulatory, cytotoxic and cytoprotective mechanism of nitric oxide. Free Radic Biol Med 25: 434-456, 1998.
Wolde ST, Engels F, Miltenburg AMM, Kuijpers EAP, Struijk-Wielinga GI, Dijkmans BAC. Sesame oil in injectable gold: two drugs in one? Br J Rheumatol 36: 1012-1015, 1997.
Yokoyama H, Mizukami T, Kamegaya Y, Fukuda M, Okamura Y, Matsumoto M, Kato S, Ishii H. Formation of superoxide anion in the hepatic sinusoid after lipopolysaccharide challenge. Alcohol Clin Exp Res 22 (3 suppl) 133S-136S, 1998.
Zhang H, Rogiers P, Friedman G, Preiser JC, Spapen H, Buurman WA, Vincent JL. Effects of nitric oxide donor SIN-1 on oxygen availability and regional blood flow during endotoxic shock. Arch Surg 131: 767-774, 1996.
Zimmerman JJ. Difinition the role of oxyradicals in the pathogenesis of sepsis. Crit Care Med 23: 616-617, 1995.