title: Changes in mRNAs of inducible nitric oxide synthase and interleukin-1 beta in the liver, kidney and lung tissues of rats acutely exposed to paraquat.
abstract: Nitric oxide (NO) reacts with superoxide to form the potent oxidant peroxynitrite, which causes serious cell damage. Interleukin-1 beta (IL-1 beta) is known to be a strong activator of NO production via induction of inducible nitric oxide synthase (iNOS). Since paraquat (PQ) undergoes redox cycling in vivo, resulting in a constant generation of superoxide, peroxynitrite may be a pathogenetic factor in the oxidative cell damage. In this study, we have investigated whether mRNAs of iNOS and IL-1 beta are affected in rat liver, kidney and lung tissues by exposure to non-lethal and lethal doses of PQ. Suppression and then marked stimulation of the iNOS mRNA were observed in the liver tissues of rats exposed to a lethal dose of PQ, while the kidney and lung tissues showed little changes. We also detected nitrotyrosine in liver tissues of rats exposed to a lethal dose by immunohistochemistry, suggesting the simultaneous generation of NO and superoxide in liver injury during acute lethal PQ poisoning. On the other hand, the IL-1 beta mRNA in the liver tissues decreased throughout the experiments, suggesting that this cytokine is not responsible for stimulation of the iNOS gene. IL-1 beta mRNA in lung tissues in the non-lethal group showed an increase, with maximum levels at 16-24 h, while little changes were observed in iNOS mRNA in this organ. These data suggest that acute lethal poisoning and non-lethal poisoning by PQ undergo different mechanisms of action of NO and IL-1 beta systems; the former is due, at least in part, to an increase in NO production, while the latter is due to stimulation of IL-1 beta and/or other cytokines.
authors.affiliation: Department of Legal Medicine, Kawasaki Medical School, Kurashiki 701-0192, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Tomita
authors.forename: T
authors.initials: T
authors.lastname: Okuyama
authors.forename: K
authors.initials: K
authors.lastname: Hidaka