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In micronodular cirrhosis, hepatocytes retain a normal C‐25 hydroxylation capacity toward vitamin D 3 : A study using the rat carbon tetrachloride–induced cirrhotic model
Author(s) -
Dubé Catherine,
Vallières Sylvie,
Éthier Chantal,
Benbrahim Nawel,
Tremblay Chantale,
GasconBarré Marielle
Publication year - 1991
Publication title -
hepatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.488
H-Index - 361
eISSN - 1527-3350
pISSN - 0270-9139
DOI - 10.1002/hep.1840130317
Subject(s) - carbon tetrachloride , cirrhosis , hydroxylation , chemistry , vitamin , medicine , biochemistry , endocrinology , enzyme , organic chemistry
To test further the competence of the cirrhotic liver to metabolize vitamin D 3 at C‐25, hepatocytes were isolated from controls and from CCl 4 ‐induced cirrhotic rat livers, as well as from partially hepatectomized rats. The transformation of D 3 into 25‐hydroxyvitamin D 3 was studied in the presence of 10 7 hepatocytes at D 3 concentrations of 20 nmol/L to 15.4 μmol/L. Histologically, micronodular cirrhosis was present in all CCl 4 ‐treated rats, whereas controls had normal livers; portal venous pressure (p < 0.008) and intrahepatic collagen content (p < 0.0001) were significantly increased in CCl 4 ‐treated rats, whereas no difference was found between the two groups in the total and ionized serum calcium, D 3 metabolites, ALT, AST and alkaline phosphatase. Cytochrome P‐450 was 0.27 ± 0.02 and 0.25 ± 0.02 nmol/10 6 hepatocytes in controls and cirrhotic rats (N.S.), and it significantly increased in both groups after phenobarbital or 3‐methylcholanthrene administration (p < 0.0001). 25‐Hydroxyvitamin D 3 formation was best described by power law equations and varied between 0.02 ± 0.0004 and 29.57 ± 2.8 in controls, and 0.024 ± 0.0004 and 32.0 ± 7.0 pmol ± hr −1 ± 10 6 hepatocytes −1 in cirrhotic rats. No statistically significant difference was found in the slopes of the 25‐hydroxyvitamin D 3 formation, but the y‐axis intercept was found to be lower in cirrhotic rats under basal resting conditions (p < 0.005). Inducers of the mixed function oxidases significantly increased 25‐hydroxyvitamin D 3 formation in controls as well as in cirrhotic rats (p < 0.005). Moreover, both groups were found to respond similarly to the addition of modulators of the enzyme such as the calcium ionophore A23187 and parathyroid hormone. Partial hepatectomy was also without effect on the activation of D 3 . Furthermore, the cell sequestration of D 3 was also found to be unperturbed in hepatocytes obtained from either cirrhotic or partially hepatectomized livers. The data indicate that in well‐compensated micronodular cirrhosis, the C‐25 hydroxylation of D 3 is generally intrinsically normal at the cellular level and that it also remains fully responsive to in vivo and in vitro modulators of its activity. (H EPATOLOGY 1991;13:489–499.)