Fasting increases the sensitivity of hepatic harmol glucuronidation to hypoxia

Abstract

Livers from fasted (N = 16) and fed (N = 22) rats were perfused with harmol (50 μM) for an initial 30 min with normal oxygen delivery (6-10 μmol/min/g liver), then for 45 min with perfusate equilibrated with O2/N2 mixtures, which reduced hepatic oxygen delivery to 0.9-6 μmol/min/g liver, and finally for a further 30 min period of normal oxygenation. Seventy per cent of the harmol eliminated was accounted for as the glucuronide conjugate and approximately 5% as the sulphate conjugate. During the hypoxia phase with fed preparations, decreasing oxygenation did not reduce harmol clearance or harmol glucuronide formation clearance until oxygen delivery was less than 2.5 μmol/min/ g liver, whereas..