Hemeoxygenase 1 inhibition exacerbates cholestatic injury in bile duct ligated rats

MARTÍN, PL; TAURIZANO, D; RAZORI, MV; MASSA, EM; ROMA, S; ROMA, MG; BASIGLIO, CL

Virtual

Congreso; Reunión Anual de la Sociedad Argentina de Fisiología (SAFIS); 2021

SAFIS

Introduction: We showed that hemeoxygenase-1 (HO1) induction, and consequent bilirubin (BR) elevation, protects the liver fromoxidative-stress (OS)-induced cholestasis in vivo. Aim: To further characterize the protective role of BR, by evaluating the effect ofHO1 inhibition at early stages of obstructive cholestasis. Methodology: Male Wistar rats were subjected to a 7-day bile-duct ligation(BDL, n=6) or sham surgery (Sh, n=5). HO1 was inhibited with Zn (II) protoporphyrin IX (PP, 25 mg/Kg b.w., i.p., 24h before BDL(PP+BDL, n=6) or Sh (PP+Sh, n=5). Blood samples were obtained before surgery (BS1) and before euthanasia (BS2), and BR, alanineaminotransferase(ALT), alkaline phosphatase (ALP) and pseudocholinesterase (CHE) were determined. Liver was removed to assesslipid peroxidation and histological damage. Results (media±SD for BS1/BS2 in Sh; PP+Sh; BDL; PP+BDL) were, respectively: BR (mg/dL)N.D./0.11±0.04; N.D./0.17±0.05; N.D./8.60±0.15a; N.D./0.50±0.08a,b. ALT(U/L) 49±6/40±4; 72±18/52±21; 153±35/206±39a;169±24/211±35a. ALP(U/L) 447±94/731±80; 469±77/740±107; 423±96/1430±184a; 487±90/1931±220a,b; CHE(U/L) 311±70/337±71;274±40/315±29; 417±60/363±70; 296±51/253±48; (a)p