Permeability changes in hepatic mitochondria and altered glucose and urea metabolism in aroclor 1254-treated rats.

Abstract

The influence of Aroclor 1254 (ARO) treatment or pair-feeding (PF) on gluconeogenesis and urea synthesis and on isolated hepatic mitochondria was studied in rats of different ages. ARO (300 mg/kg, po on 4 consecutive days) induced variable weight loss in young (153 +/- 10 g (initial wt), -10.9%), intermediate-age (195 +/- 10 g, -17.0%), and old (232 +/- 23 g, -4.9%) rats. Isolated mitochondria contained equal amounts of cytochromes aa3, b, c1 and c with exception that c1 and c were lower in the young ARO rats than in the PF controls. Mitochondria from ARO rats, which lost more weight than ad libitum-fed (AF) rats, showed suppression of ADP-stimulated H+ and oxygen uptake and succinate plus valinomycin maximal swelling in a potassium acetate and sucrose medium. Mitochondria from young ARO rats absorbed less incident light than mitochondria from PF or AF rats. Maximally swollen mitochondria from intermediate-age ARO rats, contracted more rapidly with antimycin addition than those from PF or AF controls. These findings showed greater permeability of ARO mitochondria to impermeable and accumulated ions. In contrast, mitochondria from ARO rats without significant weight loss showed activation of ADP-stimulated H+ and oxygen uptake and maximal swelling in comparison to mitochondria from AF and PF rats, but contracted like these controls after the antimycin addition. Urea synthesis in ARO rats, which lost 9.9% of initial body wt (173 +/- 6 g) and experienced a nitrogen deficit (Ebner et al., 1986), was significantly increased 12 min postinjection of NH4 acetate, and was greater than the urea level in AF rats at this time point. In comparison, gluconeogenesis was significantly increased in AF rats 12 min postinjection of NH4 acetate and was greater than in ARO rats at this time point. These differences were also observed when the data were expressed as the rate of glucose or urea appearance in peripheral blood per 100 g body wt. In PF rats, blood glucose and urea concentrations were intermediate to and indistinguishable from the ARO and AF groups. These data demonstrate that hepatic mitochondria from ARO rats that experienced a significant loss of body weight were suppressed and more permeable to ions than AF and PF controls. These mitochondrial properties may have predisposed the ARO rats toward urea formation rather than glucose synthesis and nitrogen retention.