Combinatorial impact of Chelerythrine and DADS in the restoration of liver physiology during carcinogenic exposure in mice (Mus musculus)

Abstract

Investigation of the efficacy of the combined drugs chelerythrine and DADS in restoring chemically induced hepatocellular carcinoma in Swiss albino mice. 4-6 week-old mice were considered for experimentation. The genotoxic carcinogen para-induced liver cancer--dimethyl-amino azobenzene along with nongenotoxic promoter carcinogen phenobarbital exposure. During the study, animals were co-treated with 100mg/kg body weight DADS and 5mg/kg body weight chelerythrine individually or in combination for 120 days. Bioparametric enzymatic assays of ALT, AST, ALKP, and GGT were performed. The estimation of TBARS, analysis of bone marrow chromosomal abnormalities, sperm head anomalies, and histopathological tissue structure in the co-treated group followed studies. An increase in enzymatic activities of plasma ALT, AST, ALKP, and GGT was observed after carcinogen exposure. Individual treatment of chelerythrine and DADS restored the activities mentioned above to some extent, although combined drugs successfully maintained the enzymatic activities in plasma. Changes in bone marrow chromosomal morphology and sperm head anomalies after carcinogen exposure were prevented in the individual and, most significantly, after combined drug therapy. Histopathological analysis of liver tissue of both male and female mice also demonstrated the preservation of tissue structures in the treated group, most significantly in the combined treatment, even after PB+P-DAB exposure. Chelerythrine and DADS individually protected liver tissue to a certain extent from the tumorigenic toxic effect of PB+P-DAB exposure. The combination of DADS and chelerythrine successfully guarded the tissue from any corrosive, carcinogenic impact and thus instigated further consideration as an effective alternative therapy against chemically induced hepatocarcinoma.