Liver expression of CAT-1 in rat model of acute hepatotoxicity by Thioacetamide

VIRGINIA PERDOMO; LUCIANA PRETTO; STELLA DANIELE; ANALÍA NOCITO; JAVIER PALATNIK; LUIS VEGGI

Tandil

Congreso; XL Reunión Anual de la Sociedad Argentina de Farmacología Experimental; 2008

Sociedad Argentina de Farmacología Experimental

The cationic amino acid transporter 1 (CAT-1) is expressed fairly ubiquitously in mammalian cells but its levels vary significantly in different cells and conditions. CAT-1 is required in the regenerating liver, being essential for liver cells to enter mitosis. The expression of CAT-1 is regulated by miR-122. The liver damage produced by thioacetamide (TA) in rats is a classic model of hepatotoxicity. Adult male wistar rats were treated with TA (i.p.,400 mg/kg, n=3) and saline solution (vehicle, i.p., n=3) being sacrificed 24 hs later. Serum samples were analyzed for liver markers of toxicity. Livers were extracted and used for histological and expression studies. We confirmed the hepatotoxicity in TA treated rats by Liver histopathological examination (perivenous injury) and serum toxicity markers (an increased activity of ALT, AST, ALP and LDH). We observed an induction of CAT-1 protein expression by western blot (relative expression, TA 2.01±0.49 vs C 1.00±0.28,p less than 0,05) and CAT-1 mRNA by quantitative real time PCR (relative expression, TA 27.44±7.33 vs C 1.00±0.55,p less than 0,05). We found that the expression of proliferating cell nuclear antigen (PCNA), a marker for cell proliferation, in the liver is significantly elevated in rats treated with TA by western blot (relative expression, TA 3.28±0.50 vs C 1.00±0.34,p less than 0,05). We observed by immunohistochemisty that both protein increased their expression mainly in perivenous hepatocytes. These experiments indicates that CAT-1 is induced in liver rats in zones related to cell proliferation associated to acute toxicity by TAA.