Comparison of the chemopreventive potentials of melatonin and vitamin E plus selenium on 7,12-dimethylbenz[a]anthracene-induced inhibition of mouse liver antioxidant enzymes.

Chemoprevention is a rapidly growing area of oncology that is identifying agents with a potentially preventive role in cancer. In this study, it was our goal to compare the chemopreventive effects of vitamin E plus selenium, and melatonin. Forty female mice were divided into four equal groups. The first group served as control. The second group had i.p. injections of 7,12-dimethylbenz[a]anthracene (DMBA) (20 mg/kg body weight) in corn oil for 21 days. The third group had the same procedure of DMBA injections as the second group and received vitamin E + selenium (90 microg + 1.8 microg/day), simultaneously. The fourth group had DMBA injections and melatonin (4.2 mg/kg body weight), simultaneously. DMBA alone caused significant inhibition of hepatic glutathione peroxidase (GSHPx), catalase (CAT), and superoxide dismutase (SOD) in the second group. In the third group, vitamin E + selenium restored DMBA-induced GSHPx inhibition significantly whereas CAT and SOD inhibition remained essentially unchanged. In the fourth group, melatonin not only significantly decreased DMBA-induced GSHPx inhibition but also fully reversed CAT and SOD inhibitions caused by DMBA. We speculate that melatonin alone provides better chemoprevention against DMBA-induced oxidative stress than the vitamin E+selenium combination.

Cyanogen as a selective probe for carbonic anhydrase hydrolase activity.

The salt bridge probe cyanogen (ethanedinitrile, C2N2; N identical to C-C identical to N) inhibits the bovine carbonic anhydrase (EC 4.2.1.1.) hydrolase activity toward various types of esters without significant effect on its hydrolyase activity. Two sets of pyridine derivatives that were isosteric substrates for the two activities were differentially affected. Acetazolamide and salamide are reversible inhibitors of the enzyme; only salamide affords protection of the hydrolase activity against the action of C2N2. Since each is known to bind in different positions within the active site, the selective effect of salamide may arise from its position covering one CO2 site as well as a site important for hydrolase activity. The C2N2 concentration dependence of the time course of hydrolase inhibition is consistent with the existence of a high C2N2 affinity site with slow covalent change and a second site with lower C2N2 affinity, but higher rate of covalent modification of the enzyme.