Predominance of released mitochondrial enzymes by partial hepatectomy-induced rat regenerating liver is controlled by hemodynamic changes and not related to mitochondrial damage.
OBJECTIVE
Serum activities of assumed organ-specific enzymes are useful protein markers in the diagnosis of necrotic liver diseases. However, after partial hepatectomy (PH) in rats, remaining hepatocytes proliferate to restore the lost liver mass, even when there is a drastic but selective elevation of serum enzyme activities. The aim of the present study was to elucidate the underlying mechanisms involved in this PH-induced enhancement of enzyme release.


METHODS
Routine spectrophotometric methods were used to measure nine "marker" enzyme activities in sera, in effluents from isolated perfused livers, as well as in the incubation media used for liver slices and isolated cells from either sham-operated or 70%-PH rats.


RESULTS
PH induced a drastic increase in serum activities of liver enzymes, predominantly of mitochondrial localization. In the control and 70%-PH groups, liver enzymes were differentially released by varying in vitro flow rate/liver mass ratio, using livers perfused at variable flow rates. This event was reversible and not associated with liver structural or functional alterations, but was dependent on the flow-bearing physical forces and independent of production of extra-hepatic factors. Liver slices and isolated cells were used to identify additional flow-independent enzyme release. The 70%-PH-induced drastic release of specific enzymes (predominantly those from mitochondria) could be mimicked in control livers by changing the hepatic blood flow/mass ratio, and closely resembled urea production by these livers.


CONCLUSIONS
PH-induced effects were not associated with liver necrosis or mitochondrial dysfunction and evidenced previously unrecognized mechanisms controlling the rate of enzyme release into the bloodstream, which might have clear clinical implications.
Departamento de Biología Celular, Instituto de Fisiología Celular, Universidad Nacional Autónoma de México (UNAM), Mexico.
Julieta
J
Díaz-Juárez
Lorena
L
Rivera-Valerdi
Delia E
DE
Bernal-Cerrillo
Rolando
R
Hernández-Muñoz
D000410:Alanine Transaminase / Q000097:blood*; D000818:Animals; D024442:Aspartate Aminotransferase, Mitochondrial / Q000097:blood*; D015415:Biomarkers / Q000097:blood; D001783:Blood Flow Velocity; D004195:Disease Models, Animal; D006498:Hepatectomy; D007770:L-Lactate Dehydrogenase / Q000097:blood*; D008102:Liver Circulation / Q000502:physiology*; D008107:Liver Diseases / Q000201:enzymology / Q000503:physiopathology / Q000601:surgery*; D008115:Liver Regeneration / Q000502:physiology*; D008297:Male; D008930:Mitochondria, Liver / Q000201:enzymology*; D051381:Rats; D017208:Rats, Wistar; D015427:Reperfusion Injury / Q000201:enzymology / Q000503:physiopathology / Q000601:surgery
D015415:Biomarkers; D007770:L-Lactate Dehydrogenase; D024442:Aspartate Aminotransferase, Mitochondrial; D000410:Alanine Transaminase