Hemeoxygenase 1 inhibition exacerbates cholestatic injury in bile duct ligated rats

MARTÍN, PAMELA; TAURIZANO, DENISSE; RAZORI, MARÍA VALERIA; MASSA, ESTEFANÍA; ROMA STELLA; ROMA, MARCELO G; BASIGLIO, CECILIA L

Rosario

Congreso; REUNIÓN ANUAL DE LA SOCIEDAD ARGENTINA DE FISIOLOGÍA; 2021

Sociedad Argentina de Fisiología

Introduction: We showed that hemeoxygenase-1 (HO1) induction, and consequent bilirubin (BR) elevation, protects the liver from oxidative-stress (OS)-induced cholestasis in vivo. Aim: To further characterize the protective role of BR, by evaluating the effect of HO1 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, alanine-aminotransferase (ALT), alkaline phosphatase (ALP) and pseudocholinesterase (CHE) were determined. Liver was removed to assess lipid 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