Effect of cyclosporine on hepatic energy status and on fructose metabolism after portacaval shunt in dog as monitored by phosphorus-31 nuclear magnetic resonance spectroscopy in vivo.
The effect of cyclosporin A on the hepatic energy status and intracellular pH of the liver and its response to a fructose challenge has been investigated using in vivo phosphorus-31 nuclear magnetic resonance spectroscopy in dogs. Three experimental groups were studied: (a) control dogs (n = 5), (b) dogs 4 days after the creation of an end-to-side portacaval shunt (n = 5), and (c) dogs 4 days after portacaval shunt and continuous infusion of cyclosporin A (4 mg/kg/day) by way of the left portal vein (portacaval shunt plus cyclosporin A, n = 5). The phosphorus-31 nuclear magnetic resonance spectra were obtained at 81 MHz using a Bruker BIOSPEC II 4.7-tesla nuclear magnetic resonance system equipped with a 40-cm horizontal bore superconducting solenoid. The phosphomonoesters (p less than 0.01), inorganic phosphate and ATP levels (p less than 0.05) were decreased significantly in portacaval shunt-treated and in portacaval shunt-plus-cyclosporin A-treated dogs compared with unshunted control dogs. After a fructose challenge (750 mg/kg body wt, intravenously), fructose-1-phosphate metabolism was reduced in portacaval shunt-treated dogs compared with either the normal or portacaval shunt-plus-cyclosporin A-treated dogs (p less than 0.05). Both portacaval shunt- and portacaval shunt-plus-cyclosporin A-treated dogs demonstrated a reduced decline in ATP levels after fructose infusion when compared with the controls (p less than 0.05). Immediately after the fructose challenge, the intracellular pH decreased from 7.30 +/- 0.03 to 7.00 +/- 0.05 in all animals (p less than 0.01) and then gradually returned to normal over 60 min.(ABSTRACT TRUNCATED AT 250 WORDS)
Rossaro
L
L
Department of Medicine, University of Pittsburgh School of Medicine, Pennsylvania 15261.
Mazzaferro
V
V
Scotti-Foglieni
C L
CL
Williams
D S
DS
Simplaceanu
E
E
Simplaceanu
V
V
Francavilla
A
A
Starzl
T E
TE
Ho
C
C
Van Thiel
D H
DH
D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D003524:Cyclosporins / Q000494:pharmacology*; D004285:Dogs; D004734:Energy Metabolism / Q000187:drug effects*; D005260:Female; D005632:Fructose / Q000378:metabolism* / Q000494:pharmacology; D005636:Fructosephosphates / Q000378:metabolism; D008099:Liver / Q000378:metabolism* / Q000473:pathology; D009682:Magnetic Resonance Spectroscopy; D010758:Phosphorus / Q000378:metabolism; D011167:Portacaval Shunt, Surgical; D012016:Reference Values
D003524:Cyclosporins; D005636:Fructosephosphates; C032284:fructose-1-phosphate; D010758:Phosphorus; D005632:Fructose; D000255:Adenosine Triphosphate