HEMEOXYGENASE 1 INHIBITION INDUCES A LOSS OF ANTIOXIDANT PROTECTION IN RATS WITH BILE DUCT LIGATION

TAURIZANO, D; MARTÍN, PL; RAZORI, MV; MASSA, EM; PISANI, GB; ARRIAGA, SM; SANCHEZ POZZI, EJ; ROMA MG; BASIGLIO, CL

Rosario

Congreso; Reunión Anual 2019 Sociedad Argentina de Fisiología; 2019

Sociedad Argentina de Fisiología

We had demonstrated that hemeoxygenase 1 (HO1) induction, and consequently elevated bilirubin (BR), protects the liver from oxidative stress-induced cholestatic injury in vivo. To corroborate this protective role of BR, we evaluated the effect of HO1 inhibition on endogenous BR levels and BR antioxidant capacity in animals subjected to a cholestatic insult. Wistar rats were subjected to bile duct ligation (BDL, n=6) or sham surgery (Sh, n=5). HO1 was inhibited by Zn(II) protoporphyrin IX (PP, 30 mg/Kg b.w., i.p.) administered 24h before BDL (PP+BDL, n=6) or Sh (n=5). Animals were euthanized 7 days after BDL. Blood samples were obtained before surgery (BS1) and before euthanasia (BS2) and BR, alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), gamma-glutamyltransferase (gGT) and lipid peroxidation were determined. At euthanasia, liver samples were obtained for the assessment of lipid peroxidation. Results (media±SD for BS1/BS2 in Sh; BDL; PP+BDL) were, respectively: BR(mg/dL) 0.13±0.05/0.11±0.04; 0.35±0.02/8.60±0.15a; 0.13±0.01/0.50±0.08a,b. ALT(U/L) 48±7/39±3; 136±10/188±15a; 172±32/211±21a. AST(U/L) 131±38/136±22; 385±25/474±40a; 343±49/449±36a. ALP(U/L) 570±24/707±79; 343±1/1047±84a; 510±90/1015±120a. gGT(U/L) 0.2±0.1/0.3±0.1; 0.5±0.1/12.6±3.1a; 0.8±0.1/1.5±0.2a,b; (a)p