Studies on mode of action of hexaammine Co(III) chloride against diethylnitrosamine-induced hepatocarcinogenesis in mice.
We recently reported the anticarcinogenic potential of hexaammine cobalt(III) chloride, a synthetic complex of cobalt, on diethylnitrosamine (DENA)-induced carcinogenesis. The present study was conducted to ascertain the possible mode of action of this compound on DENA-induced hepatocarcinogenesis in male BALB/c mice. Time course evaluation of liver injury markers showed that the low dose of the compound is more effective in ameliorating DENA-induced changes when administered for longer duration of time. Long-term exposure of the compound significantly reversed the levels of diacylgylcerol (DAG) and nitric oxide synthase (NOS) induced by DENA, thus suggesting that the compound may hinder the process of chemical carcinogenesis potentially by downregulating the signal transduction mechanism involving DAG and NOS. Furthermore, short-term intraperitoneal injection of the compound to mice 26 weeks after DENA initiation reduced the cell viability count in preneoplstic liver lesions in a dose-dependent manner. In conclusion, our results showed that anticarcinogenic effects of hexaammine cobalt(III) chloride result from its influence on signal transduction events mediated through DAG together with its direct cytotoxic action against preneoplastic hepatic lesions induced by DENA in mice.
Naura
Amarjit S
AS
Department of Biochemistry, Panjab University, Chandigarh-160014, India.
Sharma
Rajeshwar
R
D000477:Alkylating Agents / Q000633:toxicity*; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D014408:Biomarkers, Tumor / Q000378:metabolism*; D003035:Cobalt / Q000494:pharmacology*; D004052:Diethylnitrosamine / Q000633:toxicity*; D004075:Diglycerides / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D008099:Liver / Q000378:metabolism*; D008114:Liver Neoplasms, Experimental / Q000139:chemically induced / Q000188:drug therapy / Q000378:metabolism*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D019001:Nitric Oxide Synthase / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D013997:Time Factors
D000477:Alkylating Agents; D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D004075:Diglycerides; C030862:cobalt ammonium complex; D003035:Cobalt; D004052:Diethylnitrosamine; D019001:Nitric Oxide Synthase