Sesamol Ameliorates Cyclophosphamide-Induced Hepatotoxicity by Modulating Oxidative Stress and Inflammatory Mediators
S. Jnaneshwari, M. Hemshekhar, R.M. Thushara, M. Shanmuga Sundaram, M. Sebastin Santhosh, K. Sunitha, R.L. Shankar, K. Kemparaju and K.S. Girish
Affiliation: Department of studies and Research in Biochemistry, University of Mysore, Mysore-06 and Tumkur University, Tumkur, Karnataka, India.
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.
Keywords: Cyclophosphamide, hepatic damage, lipid peroxidation, organ toxicity, oxidative stress, sesamol.
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