Electrophilic agents Induction

Nowadays, activities of nucleic acids are controlled by interactions of Mg, Ca or Zn, but also by heavy-metal ions or electrophilic agents with certain specific sequences (e.g. in induction of metallothionein). Though this does imply NAs to act as ligands in physiological conditions, it need not imply that they could achieve the above sequence of steps, let alone the problem that up to now not even a hint of a prebiotic NA synthesis pathway was demonstrated, not even when using polyphosphoric acid in organic solvents. The E (L) values for NAs, nucleoside triphosphates or simpler species such as glycerinaldehyde-2,3-diphosphate are way too low to permit the sequence of events on their own. 

Oltipraz [4-methyl-5-(2-pyrazinyl)-l, 2-dithiole-3-thione] (OPZ), a synthetic derivative of 1, 2-dithiole-3-thione, has been extensively investigated for its chemopreventive properties first developed as an antischistosomal agent, this compound was found to increase cellular thiol levels and to induce enzymes involved in the maintenance of reduced glutathione (GSH) pools and in detoxification of electrophilic intermediates. Induction of phase 2 enzymes such as GSTs, epoxide hydrolases, and NADP(H) quinone reductases was considered to represent the key mechanism of chemoprotection of OPZ. More recently this compound was also found to modulate phase 1 enzymes, antioxidant enzymes, and other inactivating proteins, thereby indicating that its chemoprevention mechanism(s) are more complex than first envisaged. In this chapter, current information about the effects of OPZ on phase 1 and phase 2 enzymes is presented. 

PB macromolecules considerably differ in the reactivity due to the polydiene structure. The inductive effect of the alkyl substituents resulting in the increase of the electron density of the inner double bonds of macromolecules determines their high activity in the considered reactions with different electrophilic agents. 

From experiments conducted with OPZ administered before, during, and after AFBl, it was concluded that OPZ acts as a blocking rather than a suppressive chemoprotective agent [29]. Such an anti-initiating agent can, in principle, act at several levels, including inhibition or induction of CYPs, induction of phase 2 enzymes, scavenging of electrophilic metabolites and ROS, and induction of DNA repair [30]. 

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