Effects of hexaammine cobalt (III) chloride on oxidative stress-related parameters and drug metabolizing enzymes in mice.

Hexaammine cobalt (III) chloride has been advocated as a potential anticarcinogenic compound. There is no information on the effects of this compound on oxidative stress-related parameters in animals. In the present study the effects of administration of hexaammine cobalt (III) chloride in drinking water to balb/c male mice at doses of 25, 50, and 100 ppm for 14 weeks were examined. The tissue distribution of the compound was seen in liver, kidney, lung, intestine, blood, and spleen. The effects of the compound were monitored on levels of lipid peroxidation, GSH content, and activities of SOD, catalase, GST, and Cyt P450, along with the liver and kidney function tests. The results show that the cobalt accumulated maximally in kidney followed by liver, intestine, blood, spleen, and lung in decreasing order, in a dose-dependent manner. GSH and GST also showed increase in a dose-dependent manner while SOD and catalase showed increase with the highest dose only. Liver and kidney function tests showed no untoward change with any dose at the end of the study. The results suggest an antioxidant potentiating effect of the hexaammine cobalt (III) chloride besides nontoxicity to liver and kidney. Since the ability to induce an increase of GSH and GST along with other detoxifying enzymes by anticarcinogenic agents has been reported to correlate with the inhibition of tumorigenesis, the cobalt complex might qualify as a potential cancer chemopreventive agent.

Effect of monensin, a Na+-specific carboxylic ionophore on the oxidative defense system in rat testis.

The effect of monensin, a Na+-specific ionophore on the oxidative defense system in rat testis was studied. Monensin mixed in the animal diet was administered at the dose levels of 2.5, 5 and 10 mg/kg b.w. to Wistar rats for a period of 67 days. A marked inhibition in the activities of different oxidative defense enzymes such as catalase, glutathione peroxidase, glutathione-S-transferase, superoxide dismutase and glutathione reductase was noticed, which indicates the possible involvement of free radicals in the antispermatogenic effects of monensin in rat testis. This was further substantiated by a significant increase in the generation of lipid peroxides along with the depletion of reduced glutathione. The drug treatment resulted in a significant change in apoptotic cell death as seen by an elevated fragmentation in the testicular genomic DNA. Monensin treatment also resulted in marked degenerative changes in the histoarchitecture of testis, such as depletion of different germ cell populations, vacuole formation and disorganization of seminiferous tubules. The results are indicative of the potential antispermatogenic effects of monensin in the rat.

Anticarcinogenic effects of hexaamminecobalt(III) chloride in mice initiated with diethylnitrosamine.

Hexaamminecobalt(III) chloride ([Co(NH3)6]Cl3) was investigated for its antineoplastic role in relation to tumor marker enzymes, drug metabolizing enzymes, oxidative stress-related parameters, and histopathological analysis of liver and lung tissues of mice. Initiation was performed using a single intraperitoneal injection of diethylnitrosamine (DENA) at a carcinogenic dose of 90 mg/kg body weight. The cobalt complex supplementation at a dose of 100 ppm in drinking water was given ad libitum throughout the experimental period of 14 weeks. In comparison to lung, the cobalt complex supplementation was found to reverse DENA-induced biochemical changes more effectively in liver. Histological examination of liver and lung from DENA-initiated and cobalt-complex-supplemented mice showed considerable protection in the case of liver compared to that of lung. The involvement of the [Co(NH3)6]Cl3 in modulating several factors associated with carcinogenesis induced by DENA thus showed its anticarcinogenic potential against chemically induced hepatocarcinogenesis.