Role of Parathyroid Hormone in the Downregulation of Liver Cytochrome P450 in Chronic Renal Failure | Zendy

Josée Michaud | Zendy; Judith Naud | Zendy; JéroCombining Circumflex Accentme Chouinard | Zendy; FrancCOMBINING CEDILLAois Désy | Zendy; Agnès Leblond | Zendy; Karine Desbiens | Zendy; Alain Bonnardeaux | Zendy; Vincent Pichette | Zendy

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Role of Parathyroid Hormone in the Downregulation of Liver Cytochrome P450 in Chronic Renal Failure

Author(s) -

Josée Michaud,

Judith Naud,

JéroCombining Circumflex Accentme Chouinard,

FrancCOMBINING CEDILLAois Désy,

Agnès Leblond,

Karine Desbiens,

Alain Bonnardeaux,

Vincent Pichette

Publication year - 2006

Publication title -

journal of the american society of nephrology

Language(s) - English

Resource type - Journals

SCImago Journal Rank - 4.451

H-Index - 279

eISSN - 1533-3450

pISSN - 1046-6673

DOI - 10.1681/asn.2006010035

Subject(s) - parathyroid hormone , downregulation and upregulation , cytochrome p450 , medicine , endocrinology , chronic renal failure , hormone , chemistry , metabolism , calcium , biochemistry , gene

Chronic renal failure (CRF) is associated with a decrease in drug metabolism secondary to a decrease in liver cytochrome P450 (P450). The predominant theory to explain this decrease is the presence of factors in the blood of uremic patients. This study tested the hypothesis that parathyroid hormone (PTH) could be this factor. The objectives of this study were to determine (1) the role of PTH in the downregulation of hepatocyte P450 induced by rat uremic serum, (2) the role of PTH in the downregulation of liver P450 in rats with CRF, and (3) the effects of PTH on P450 in hepatocytes. For this purpose, (1) hepatocytes were incubated with serum from rat with CRF that was depleted with anti-PTH antibodies or with serum from parathyroidectomized (CRF-PTX) rat with CRF, (2) the effect of PTX on liver P450 was evaluated in rats with CRF, and (3) the effects of PTH on P450 in hepatocytes were determined. The depletion of PTH from CRF serum completely reversed the downregulating effect of CRF serum on P450 in hepatocytes. Addition of PTH (10(-9) M) to depleted CRF serum induced a decrease in P450 similar to nondepleted CRF serum. The serum of CRF-PTX rats had no effect on P450 in hepatocytes compared with CRF serum. Adding PTH to CRF-PTX serum induced a similar decrease in P450 as obtained with CRF serum. Finally, PTX prevented the decrease of liver P450 in rats with CRF. In summary, PTH is the major mediator implicated in the downregulation of liver P450 in rats with CRF.

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