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.
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.
Tomita
M
M
Department of Legal Medicine, Kawasaki Medical School, Kurashiki 701-0192, Japan.
Okuyama
T
T
Hidaka
K
K