The action of Isoflurane and Sevoflurane on some hemeproteins in a murine genetic model of Acute Intermittent Porphyria. Evaluation of hepatic damage and the instauration of oxidative stress

RUSPINI, SILVINA; ZUCCOLI, JOHANNA; LAVANDERA, JIMENA; BATLLE ALCIRA; BUZALEH ANA MARIA

Dusseldorf

Congreso; INTERNATIONAL CONGRESS ON PORPHYRINS AND PORPHYRIAS 2015; 2015

Isofluraneand Sevoflurane reproduced the typical biochemical signs of Acute IntermittentPorphyria (AIP) when they were administered to CF1 mice. The effects on the Porphobilinogen deaminase (PBG-D)deficient model were more pronounced, indicating a high sensibility to these anaestheticsthat confirmed their porphyrinogenicity.  The aim was to evaluate if there are othermetabolisms, related to the heme pathway, affected by volatile anaestheticsthat could contribute to the known symptomatology observed in porphyricpatients. The activities of Catalase, tryptophan pyrrolase (TRP), glutathionetransferase (GST) and glutathione (GSH) levels were measured in T1 (PBG-Dreduced 50%) and AIP (PBG-D reduced 70%) mice of both sexes received one doseof 2 ml/kg (Isoflurane) or 1.5 ml/kg (Sevoflurane). When Isoflurane wasadministrated to T1 male mice, the activity of Catalase increased in liver(155%, p<0.01), kidney (275%, p<0.01) and encephalon (70%, p<0.05)without any effect in T1 females or AIP groups. In AIP female mice, Isofluraneaffected the kidney, reducing 60% (p<0.01) TRP activity and increasing (50%,p<0.05) GSH levels while liver GST was 55% (p<0.05) increased. Sevofluraneonly altered Catalase in encephalon T1 male mice, reducing 65% (p<0.05) itsactivity. On the contrary, in AIP mice Catalase activity increased in male liver(30%, p<0.05) and in male (50%, p<0.05) and female encephalon (238%,p<0.05). In conclusion, biochemical alterations in the different parametersthat varied according to sex and mutation were observed. The changes in GSH levelsand Catalase in AIP mice seem to indicate the instauration of oxidative stress,and the variation of TRP showed an alteration in the regulatory heme pool.