Thioacetamide impairs hepatocyte ureagenesis from ammonia, but not from glutamine or alanine: involvement of mitochondrial aquaporin-8.

ALVAREZ, MARÍA DE LUJÁN; CAPIGLIONI, ALEJO; MARINELLI, RAÚL ALBERTO

Rosario

Congreso; Reunión Anual 2019 de la Sociedad Argentina de Fisiología; 2019

Sociedad Argentina de Fisiología (SAFIS)

Urea is synthetized by hepatocytes as the major end product of nitrogen metabolism and urea production is used as a key marker for hepatocyte functional capacity. Thioacetamide (TAA) is a well-known hepatotoxic agent.Nevertheless, studies on TAA toxicity in rat hepatocytes under similar conditions have reported either reduced or not altered urea synthesis. To clarify this issue, we studied the effect of TAA (0?30 mM for 24 h) on urea synthesisfrom ammonia, glutamine or alanine in primary cultured rat hepatocytes. It is of note that free ammonia has to diffuse into mitochondria, while amino acids represent an intramitochondrial source of ammonia. TAA significantlyimpaired urea synthesis from ammonia (Control: 100 ± 4%; TAA-10mM: 81 ± 8%; TAA-20mM: 69 ± 9%*; TAA30mM: 69 ± 9%*; data are means ± SEM; n=6; *P