The study aimed to investigate the antitumor effect of tetrodotoxin (TTX) and/or doxorubicin (DOX) on Ehrlich ascites carcinoma (EAC)-bearing mice through the investigated biochemical parameters. TTX and/or DOX with or without N-acetylcystiene were administrated after 10 days into EAC-female mice for a period of 2 weeks in six equal doses. Treatment with TTX or DOX caused a significant decrease in the mean tumor weight and an increase in the cumulative mean survival time when compared with EAC group. All the treatments reduced the elevated liver tumor markers and increased liver antioxidant enzymes under investigation in comparison with EAC. Hepatic cells, suffered severely from degeneration and karriolysis in EAC group, revealed some improvement as appearance of healthy hepatocytes by TTX treatment. The present results suggested that TTX had a more powerful inhibitor effect on EAC growth than DOX and TTX plus DOX treatments reflected by antitumor biochemical and histological studies.

Objective: Rifampicin (RIF) could be a recognized therapeutic and preventive agent against tuberculosis. Still, high rates of many side effects and symptoms related to hepatotoxicity have identified during treatment. So, the current study was aimed to evaluate the antioxidant and hepatoprotective activity of methanolic extract of Annona Squamosa Linn (MEAS) and N-Acetyl Cysteine (NAC) against RIF induced hepatic injury in male rats. Methods: The hepatoprotective effects of MEAS (500 mg/kg b.wt.) and NAC (100 mg/kg b.wt.) or co-treatment were assessed in a model of hepatotoxicity by RIF (300 mg/kg b. wt.) in male rats daily for 21 d. Moreover, bilirubin, total protein, albumin, ALT, AST, ALP, GGT, MDA, and GSH were estimated. In addition, the levels of IL-6, IL-10, 8(OH)dG, and Bcl2 were evaluated. Results: The oral administration of MEAS and NAC or their combination resulted in significant reductions in the levels of bilirubin, albumin, hepato-specific markers namely ALT, AST, ALP, GGT, and MDA as compared to the RIF group. Furthermore, MEAS and NAC or the combination of MEAS and NAC treatment significantly up-regulated the levels of total protein, glutathione reductase with concomitant decrease in inflammatory marker level IL-6 and apoptotic marker level 8(OH)dG as well as increment the level of anti-inflammatory marker IL-10 and anti-apoptotic marker Bcl2 as compared to the RIF group. Histological examination of the liver tissue indicated that co-treatment with MEAS and NAC completely abolished the inflammation and degeneration in hepatocytes and restore the liver tissue to its normal structure. Conclusion: The present findings demonstrated that a co-treatment of MEAS and NAC seems to be more productive and curative than alone MEAS or NAC treatment and strongly compensated the liver damage induced by RIF.