帝鉑是臨床上重要的抗癌藥物，它可以用來治療多類型的癌症。然而，它會產生腎毒性和肝毒性等副作用。氧化性壓力的產生可能是帝鉑誘發的腎毒性和肝毒性的原因之一。研究指出芝麻油可以減輕氧化性壓力及改善肝腎傷害，而芝麻油對帝鉑所引起的氧化性壓力和肝腎毒性的影響仍不清楚。因此本研究目的為探討芝麻油是否能對抗帝鉑所引起的氧化性壓力和肝腎毒性，且不會影響到帝鉑抗癌的藥效。在此實驗中，給予小鼠以腹腔注射帝鉑(20 mg/kg BW)並同時灌食芝麻油(8 ml/kg BW/day)，之後再持續灌食兩天後犧牲。進行肝腎切片及採集血液和肝腎組織樣本，測定超氧化陰離子、羥自由基、過亞硝酸基、一氧化氮含量、脂質過氧化反應、測定肝腎功能指標及觀察肝腎切片，此外每三天一次測量腫瘤成長情形。結果顯示，給予芝麻油可以降低帝鉑引起之超氧化陰離子、過亞硝酸基、羥自由基的生成、脂質過氧化反應，改善肝腎功能異常來減輕肝腎傷害，不會減低帝鉑抑制腫瘤的藥效。本研究結論，芝麻油可以降低氧化壓力來改善帝鉑所引起的肝腎傷害，不影響帝鉑在黑色素細胞癌的治療藥效。

Cisplatin is one of the most important antineoplastic agents used for several types of solid tumors; however, a number of side effects of cisplatin have been reported, including hepatotoxicity and nephrotoxicity. Recent studies indicate that oxidative stress plays an important role in the pathogenesis of cisplatin-associated organ toxicity. Sesame oil, a potent antioxidant, reduces reactive oxygen species and lipid preoxidation, and attenuates multiple organ failure during oxidative stress. However, the effects of sesame oil on cisplatin-induced hepatic and renal injuries have never been reported. The aim of present study was to assess the protective effects of sesame oil against cisplatin-induced oxidative stress-associated hepatic and renal injuries in mice. Oxidative stress-associated hepatic and renal injuries were induced by single dose of cisplatin (20 mg/kg, ip) in mice. Sesame oil (8 ml/kg, po) was given daily for three days. Sesame oil reduced lipid peroxidation and attenuated hepatic and renal injuries. Sesame oil significantly decreased cisplatin-induced hydroxyl radical, superoxide anion, peroxynitrite, and nitric oxide productions. In addition, sesame oil did not affect the anti-tumor efficacy of cisplatin against skin tumor in mice. It was suggested that sesame oil could reduce the cisplatin-induced organ toxicity by inhibiting oxidative stress without affecting the anti-tumor efficacy of cisplatin.

Anand AJ, Bashey B. Newer insights into cisplatin nephrotoxicity. Ann Pharmacother 27:1519-1525, 1993.
Antunes LMG, Darin JDC, Bianchi MDP. Protective effects
of vitamin C against cisplatin-induced nephrotoxicity and lipid peroxidation in adult rats: A dose-dependent study. Pharmacol
Res 41:405-411, 2000.
Appenroth D, Frob S, Kersten L, Splinter FK, Winnefeld K. Protective effects of vitamin E and C on cisplatin nephrotoxicity in developing rats. Arch Toxicol 71:677-683, 1997.
Baliga R, Ueda N, Walker PD, Shah SV. Oxidant mechanisms in toxic acute renal failure. Drug Metab Rev 3:971-997, 1999.
Baliga R, Zhang Z, Baliga M, Ueda N, Shah SV. In vitro and in vivo evidence suggesting a role for iron in cisplatin-induced nephrotoxicity. Kidney Int 53:394-401, 2001.
Comporti M. Lipid peroxidation and cellulardamage in toxic liver injury. Lab Invest 53:599-623, 1985.
Crul, M., Schellens, J.H.M., Beijnen, J.H. and Maliepaard, M. Cisplatin resistance and DNA repair. Cancer Treat. Rev 23: 341-366.1997.
Cersosimo RJ. Hepatotoxicity associated with cisplatin chemotherapy. Ann Pharm 27:438-441, 1993.
Calvert AH, Harland SJ, Newell DR. Early clinical studies with cis-diammine-1,1-cyclobutane dicarboxylate platinum II. Cancer Chemother Pharmacol 9:140-147, 1982.
Campbell KCM, Rybak LP, Meech RP, Hughes L. Dmethionine provides excellent protection from cisplatin ototoxicity in the rat. Hear Res 102:90-98, 1996.
Choie DD, Longnecker DS, Del Campo AA. Acute and chronic cisplatin nephropathy in rats. Lab Invest 44:397-402, 1981.
Chen YC, Lin-Shiau SY, Lin JK. Involvement of reactive oxygen species and caspase 3 activation in arsenite induce apoptosis. J Cell Physiol 177:324-333, 1988.
Chak I, Ozbek H, Karaayvaz M, Ozturk HS. Cisplatin induces acute renal failure by impairing antioxidant system in guinea pigs: effects of antioxidant supplementation on the cisplatin nephrotoxicity. Drug Chem Toxicol 25:1-8, 2002.
Cummings BS, Schnellmann RG. Cisplatin-induced renal cell apoptosis: Caspase 3-dependent and -independent pathways. J Pharmacol Exp Ther 302:8-17, 2002.
Cavalli F, Tschopp L, Sonntag RW, Zimmerman A. A case of liver toxicity following cis-dichlorodiammineplatinum(II) treatment. Cancer Treat Rep 62:2125-2126, 1978.
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.
Dobyan DC, Levi J, Jacobs C, Kosek J, Weiner MW. Mechanism of cis-platinum nephrotoxicity: Morphologic observations. J Pharmacol Exp Ther 213: 551-556, 1980.
Davis CA, Nick HS, Agarwal A. Manganese superoxide dismutase attenuates cisplatin-induced renal injury: importance of superoxide. J Am Soc Nephrol. 12:2683-2690, 2001.
De Groot CJ, Ruuls SR, Theeuwes JW, Dijkstra CD ,Van der Valk P. Immunocytochemical characterization of the expression of inducible and constitutive isoforms of nitric oxide synthase in demyelinating multiple sclerosis lesions. J Neuropathol Exp Neurol 56:10-20, 1997.
Eastman A . Mechanisms of resistance to cisplatin, in Molecular and Clinical Advances in Anticancer Drug Resistance Ozols RF ed 24:233-249, 1991.
Fleck C, Kretzschel I, Sperschneider T. Renal amino acid transport in immature and adult rats during chromate and cisplatinum-induced nephrotoxicity. Amino Acids 20:201-215, 2001.
Gtteridge JMC. Lipid peroxidation and antioxidants as biomarkers of tissue damage. lin Chem 41:1819-1828, 1995.
Goligorsky MS, Brodsky SV, Noiri E. Nitric oxide in acute renal failure: NOS versus NOS. Kidney Int. 61:855-861, 2002.
Glasco A, Lippard SJ. Anticancer activity of cisplatin and related compounds. Top Biol Inorg Chem 1:1-43, 1993.
Goldstein RS, Mayor GH. The nephrotoxicity of cisplatin. Life Sci 32:685–690, 1983.
Godwin A, Meister A, O’Dwyer P, Huang C, Hamilton M, Anderson M. High resistance to cisplatin in human ovarian cell lines is associated with marked increase glutathione synthesis. Proc Natl Acad Sci USA 89:3070-3074, 1992.
Gutteridge JMC, Mitchell J. Redox imblance in the critically ill. Br Med Bull 55:49-75, 1999.
Giri A, Khynriam D, Prasad SB. Vitamin C mediated protection on cisplatin-induced mutagenicity in mice. Mut Res 421: 139–48, 1998.
Hsu DZ, Chiang PJ, Chien SP, Huang BM, Liu MY. Parenteral sesame oil attenuates oxidative stress after endotoxin intoxication in rats. Toxicology 196:147-153, 2004.
Hartmann JT, Fels LM, Knop S. A randomized trial comparing the nephrotoxicity of cisplatin/ifosfamide-based combination chemotherapy with or without amifostine in patients with solid tumors. Invest New Drugs 18:281-289, 2000.
Halliwell B, Gutteridge JMC. Lipid peroxidation: a radical chain reaction. In: Halliwell B, Gutteridge JMC. (Eds.), Free radicals in biology and medicine. Clarendon Press, Oxford, UK 13:188-276, 1999.
Hibino Y, Kamiuchi S, Kusashio E, Sugano N. Enhancement of DNA repair activity in rat-liver cells exposed to cisplatin. Biochem. Mol. Biol Int. 38:973-979, 1996.
Hsu DZ, Liu MY. Sesame oil attenuates multiple organ failure and increase survival rate during endotoxemia in rats. Critical Care Medicine 30:1859-1862, 2002.
Hsu DZ, Liu MY. Effects of sesame oil on oxidative stress after the onset of sepsis in rats. Shock 22:582-585, 2004.
Hsu DZ, Liu MY. Sesame oil protects against lipopolysaccharide-stimulated oxidative stress in rats. Critical Care Medicine 32:227-231, 2004.
Hsu DZ, Li YH, Chien SP, Liu MY. Effects of sesame oil on oxidative stress and hepatic injury after cecal ligation and puncture in rats. Shock 21:466-469, 2004.
Husain K, Morris C, Whitworth C, Trammell GL, Rybak LP, Somani, SM. Protection by ebselen against cisplatin-induced nephrotoxicity: antioxidant system. Mol Cell Biochem 178:127-133, 1998.
Hrushesky WJ, Shimp W, Kennedy BJ. Lack of age-dependent
cisplatin nephrotoxicity. Am J Med. 76:579-584, 1984.
Huang Y, Zhou S, Qui L, Wu J, Xu C. Effects of zinc gluconate on nephrotoxicity and glutathione metabolism disorder induced by cisplatin in mice. Drug Metab. Drug Interact. 14: 41-46, 1997.
Ignarro LJ, Cirino G, Casini A, Napoli C. Nitric oxide as a signaling molecule in the vascular system: an overview. J Cardiovasc Pharmacol 34:879-883, 1999.
Iino K, Iwase M, Sonoki K, Yoshinari M. Combination treatment of vitamin C and desferrioxamine suppresses glomerular superoxide and prostaglandin E production in diabetic rats. Diabetes Obes Metab 7:106-109, 2005.
Jamieson ER, Lippard SJ. Structure, recognition, and processing of cisplatin-DNA adducts. Chem Rev 99:2467-2498, 1999.
Kakkar B, Das PN, Viswanathan. Modified spectrophotometric assay of SOD. Ind J Biochem Biophys 21:130-132, 1984.
Kamal EA, Pettersson D, Appelqvist LA. Sesamin (a compound from sesame oil) increases tocopherol levels in rats fed ad libitum. Lipids 30:499-505, 1995.
Kang MH, Naito M, Tsujihara N, Osawa T. Sesamolin inhibits lipid peroxidation in rat liver and kidney. J Nutr 128:1018-1022, 1998.
Kaur IP, Saini A. Sesamol exhibits antimutagenic activity against oxygen species mediated mutagenicity. Mutat Res 470:71-76, 2000.
Kirkebo’en KA, Strand QA. The role of nitric oxide in sepsis- an overview. Acta Anaesthesiol Scand 43:275-288, 1999.
Komers R, Lindsley JN, Oyama TT, Anderson S. Effects of long-term inhibition of neuronal nitric oxide synthase (NOS1) in uninephrectomized diabetic rats. Nitric Oxide 11:147-155, 2004.
Kruidering M, van de Water B, de Heer E, Mulder GJ, Nagelkerke JF.
Cisplatin-induced nephrotoxicity in porcine proximal tubular cells, mitochondrial dysfunction by inhibition of complexes I to IV of the respiratory chain. J Pharmacol Exp Ther 280:638-649, 1997.
Kukreja RC, Kontas A, Hess ML, Ellis ES. PG synthase and lipoxygenase generates superoxide in the presence of NAD or NADPH. Circ Res 59:612-619, 1986.
Lau AH. Apoptosis induced by cisplatin nephrotoxic injury. Kidney Int 56:1295-1298, 1999.
Lebwohl D, Canetta R. Clinical development of platinum complexes in cancer therapy: an historical perspective and an update. Eur J Cancer 34:1522-1534, 1998.
Lieberthal W, Triaca V, Levine J. Mechanisms of death induced by cisplatin in proximal tubular epithelial cells: apoptosis vs. necrosis. Am J Physiol 270:F700-F708, 1996.
Lindauer E, Holler E. Cellular distribution and cellular reactivity of platinum(II) complexes. Biochem Pharmacol 52:17-24, 1996.
Matsushima H, Yonemura K, Ohishi K, Hishida A. The role of oxygen free radicals in cisplatin-induced acute renal failure in rats. J Lab Clin Med 131:518-526, 1998.
Mollman JE, Glover DJ, Hogan WM, Furman RE.Cisplatin neurophaty risk factors, prognosis and protection by WR-2721. Cancer 61:2192-2195, 1998.
Mora Lde O, Antunes LM, Francescato HD, Bianchi Mde L: The effects of oral glutamine on cisplatin-induced nephrotoxicity in rats. Pharmacol Res 47:511-522, 2003.
Nazýroglu M: Enhanced testicular antioxidant capacity in streptozotocin induced diabetic rats: protective role of vitamins C, E and selenium. Biol Trace Elem Res 94:61-71, 2003.
Nisar S, Feinfeld DA. N-Acetylcysteine as salvage therapy in cisplatin nephrotoxicity. Renal Fail 24:529-533, 2002.
Ozen S, Akyol O, Iraz M, Sogut S, Ozugurlu F, Ozyurt H, Odaci E, Yildirim Z. The role of caffeic acid phenethyl ester, an active component of propolis, against cisplatin-induced nephrotoxicity in rats. J Appl Toxico 24:27-35, 2004.
Peyrone M. Cisplatin .Ann Chemie Pharm 51:129, 1845.
Placer ZA, Cushman L, Johnson BC. Estimation of products of lipid peroxidation (malonyl dialdehyde) in biological fluids. Anal Biochem 16:359-364, 1996.
Rosenberg B, Vancamp L, Krigas T. Inhibition of cell division in Escherichia coli by electrolysis products from a platinum electrode. Nature 205:698-699, 1965.
Rosenberg, B. Fundamental studies with cisplatin. Cancer 55: 2303-2315, 1985.
Safirstein RL. Lessons learned from ischemic and cisplatin-induced nephrotoxicity in animals. Renal Failure 21:359-361, 1999.
Sueishi K, Mishima K, Makino K, Itoh Y, Tsuruya K, Hirakata H, Oishi R. Protection by a radical scavenger edaravone against cisplatin-induced nephrotoxicity in rats. Eur J Pharmacol 451: 203-208, 2002.
Sugihara K, Gemba M. Modification of cisplatin toxicity by antioxidants. Jpn J Pharmacol 40:353-355, 1986.
Tsutsumishita Y, Onda T, Okada K, Takeda M, endou H, Futaki S, Niwa M. Involvement of H2O2 production in cisplatin-induced nephrotoxicity. Biochem Biophys Res Commun 242:310-312, 1998.
Walker EM Jr, Gale GR. Methods of reduction of cisplatin nephrotoxicity. Ann Clin Lab Sci 11:397-410, 1981.
Weijl, N.I., Cleton, F.J. and Osanto, S. Free radicals and antioxidants in chemotherapy-induced toxicity. Cancer Treat. Rev. 23: 209-240, 1997.
Yildirim Z, Sogut S, Odaci E, Iraz M, Ozyurt H, Kotuk M, Akyol. Oral erdosteine administration attenuates cisplatin-induced renal tubular damage in rats. Pharmacol Res 47:149-156, 2003.
Zhang JG, Viale M, Esposito M, Lindup WE. Tiopronin protects against the nephrotoxicity of cisplatin in the rat. Hum Exp Toxicol 18:713-717, 1999.