Jnaneshwari S, Hemshekhar M, Thushara R M, Sundaram M Shanmuga, Santhosh M Sebastin, Sunitha K, Shankar R L, Kemparaju K, Girish K S
Department of studies and Research in Biochemistry, University of Mysore, Mysore-06 and Tumkur University, Tumkur, Karnataka, India.
Anticancer Agents Med Chem. 2014;14(7):975-83. doi: 10.2174/1871520613666131224123346.
In current scenario of human health and diseases, drug-induced hepatic injury has been recognized as a serious and unresolved problem. Particularly, chemotherapeutic agents have been reported to induce organ toxicity. The aim of the present study is to evaluate organ toxicity and oxidative damage induced by cyclophosphamide (CP), a chemotherapeutic drug and its amelioration by sesamol, an antioxidant from sesame seeds. CP (150 mg/kg) is injected intraperitonially to experimental rats and from day 2 rats were orally treated with sesamol. Rats were sacrificed to evaluate non-enzymatic and enzymatic oxidative stress parameters in serum and tissue homogenates on day 8. Besides, liver function parameters and pro-inflammatory mediators were assessed. Histopathological studies of liver and kidney were also carried out. Elevated levels of endogenous reactive oxygen species, lipid peroxidation and decreased levels of glutathione, total thiols, along with the reduction in antioxidant enzymes including superoxide dismutase, catalase, glutathione-stransferase and glutathione peroxidase, were evident in CP-intoxicated animals. Pro-inflammatory mediators like tumor necrosis factor - α, interleukin (IL)-1β, IL-6 and cyclooxygenase-2 were also elevated. Moreover, the levels of liver function markers like serum alanine aminotransferase and aspartate aminotransferase were also altered. Histology of liver and kidney tissues further supported CP-induced organ damage. Altered parameters were significantly restored to normal by oral administration of sesamol (50 mg/kg) suggesting its antioxidative stress, anti-inflammatory and hepatoprotective abilities. The study clearly demonstrated the potentiality of sesamol against CPinduced organ toxicity and oxidative stress suggesting its applicability in treatment regime of cancer and other stress-associated disorders as a supportive/auxiliary therapy.
在当前人类健康与疾病的背景下，药物性肝损伤已被公认为一个严重且尚未解决的问题。特别是，据报道化疗药物会引发器官毒性。本研究的目的是评估化疗药物环磷酰胺（CP）诱导的器官毒性和氧化损伤，以及芝麻籽中的抗氧化剂芝麻酚对其的改善作用。将CP（150毫克/千克）腹腔注射给实验大鼠，从第2天起给大鼠口服芝麻酚。在第8天处死大鼠，以评估血清和组织匀浆中的非酶促和酶促氧化应激参数。此外，还评估了肝功能参数和促炎介质。同时也对肝脏和肾脏进行了组织病理学研究。在CP中毒的动物中，内源性活性氧水平升高、脂质过氧化增加、谷胱甘肽、总硫醇水平降低，同时包括超氧化物歧化酶、过氧化氢酶、谷胱甘肽-S-转移酶和谷胱甘肽过氧化物酶在内的抗氧化酶活性降低，这些变化都很明显。肿瘤坏死因子-α、白细胞介素（IL）-1β、IL-6和环氧化酶-2等促炎介质水平也升高。此外，血清丙氨酸氨基转移酶和天冬氨酸氨基转移酶等肝功能标志物水平也发生了改变。肝脏和肾脏组织的组织学进一步证实了CP诱导的器官损伤。口服芝麻酚（50毫克/千克）可使改变的参数显著恢复正常，表明其具有抗氧化应激、抗炎和肝保护能力。该研究清楚地证明了芝麻酚对抗CP诱导的器官毒性和氧化应激的潜力，表明其作为一种支持性/辅助治疗方法在癌症和其他应激相关疾病治疗方案中的适用性。
