Effect of the dietary brominated phenol, lanasol, on chemical biotransformation enzymes in the gumboot chiton Cryptochiton stelleri (Middendorf, 1846).

The effects of diet and other non-anthropogenic stressors on biochemical defenses and their relationship to susceptibility have been largely ignored in wildlife populations. Lanosol is a compound found in relatively high amounts in various marine species of Rhodophyta, including Odonthalia dentata. While previous studies demonstrated that lanosol is a feeding deterrent to several marine herbivores, Cryptochiton stelleri readily feeds upon O. dentata. To examine the effects of lanosol on the profile of biochemical defenses in C. stelleri, chitons were gavaged daily with 0, 1, 2.5, 5, or 10 mg/kg of lanosol. After three days of exposure, digestive gland microsomes were probed for expression of homologous isoforms of cytochromes P450 (CYP1A, CYP3A, and CYP2) and phase II enzymatic activities. Expression of a 43 kDa CYP3A-like protein was increased by approximately 45%, over control following 2.5, 5, and 10 mg/kg treatments. Estradiol hydroxylase activity tended to increase with the dose of lanosol. UDP-glucuronosyl transferase activity was highly variable but appeared to increase at the two highest treatments, while sulfotranserase activity was significantly decreased at the three highest doses. Kinetic studies of GST activity showed lanosol is a non-competitive inhibitor of both CDNB and GSH in the GST-mediated conjugation reaction. These results show that dietary exposure to the brominated-phenol, lanosol, may alter expression and activity of some phase I and II biotransformation enzymes in chitons, potentially providing a dietary advantage for the species.

Inhibition on inducible nitric oxide synthase.

The scientific community has witnessed an exponential growth curve in the number of nitric oxide (NO) related publications over the last ten years. This diatomic radical is remarkably entangled (directly and indirectly) in a multitude of physiological and pathophysiological processes, including blood pressure regulation, inflammation, apoptosis, platelet adhesion, neurotransmission and host-defense mechanisms. Of the three known isozymes responsible for catalyzing the production of NO from L-arginine (L-Arg), it is the inducible form of nitric oxide synthase (iNOS) that we wish to examine here due to its involvement in a collection of diseases, including septic- and cytokine-induced shock, immune-type diabetes, rheumatoid arthritis, tissue damage, inflammation, and inflammatory bowel disease. Controlling the unregulated overproduction of NO from iNOS has been a formidable task; therapeutic intervention strategies range from preventing iNOS mRNA expression (anticytokine antibodies/receptor antagonists) to impeding NO action (NO scavengers, guanylyl cyclase inhibitors). Within these extremes lies the most conventional tactic, prohibiting NO production from iNOS with L-arginine competitive antagonists or irreversible enzyme inhibitors. This review will cover the more recent accounts gauged toward the identification and development of novel inhibitors of iNOS.