Abstract
Hepatocellular carcinoma (HCC) considers the most common type of primary liver cancer and the fourth cause of cancer death worldwide. Doxorobcin is widely used in chemotherapy but it has many side effects. L-arginine is one of amino acids that could use for many cancer treatments as its metabolism impairs T-cell responses that would remove the tumor cells. Therefore, the aim of the current study is to compare the role of the L-arginine, doxorobcin or their combination in ameliorating HCC-induced changes on the mice liver like the nitric oxide (NO) verproduction and arginase expression downregulation. NO plays an important role in various tumors as it can modulate tumor growth progression via a series of redox reactions. Arginase is known to regulate oxidative stress in various degenerative diseases by modulating NO. Fifty mice were used in the present study (10 mice each): control mice (G.I), mice that received hepatocellular carcinoma cells (HEPG2) at a dose 1 x 10(6) (G. II), mice that received doxorubicin (G. III) at a dose 2 mg/kg, L-argninine (GI. V) at a dose 1.5 g/kg B.wt. or their combination (G. V) at at the same previous doses followed by HEPG2 cell, respectively. HEPG2 injected mice showed an increase in the liver NO, upregulation in the expression of transforming growth factor beta (TGFB1), a decrease in the liver arginase and serum adiponictin (ADIPOQ) and downregulation in the expression of the arginase gene. Both doxorubicin, L-arginine or their combination decreased NO level and hence caused an increment of arginase activity. Also, they improved the serum ADIPOQ and upregulate its gene expression. Remarkabely, the effect of L-arginine is more dominant. So, L-arginine is potential than doxorubicin or their combination in improving hepatocellular carcinoma via improving nitric oxide overproduction and arginase expression downregulation.