Therapeutic efficacy of decreased nitrite production by bezafibrate in patients with primary biliary cirrhosis.
BACKGROUND
The therapeutic efficacy of bezafibrate, a hypolipidemic drug, has been shown in patients with primary biliary cirrhosis (PBC) in some pilot studies; however, little is known regarding the mechanism of action of bezafibrate in PBC. This study was conducted to evaluate the therapeutic efficacy, as well as to gain insight about the possible mechanism of action, of bezafibrate in PBC.


METHODS
Sixteen patients with PBC were administered with bezafibrate (400 mg/day) either with (n = 10) or without ursodeoxycholic acid (UDCA; n = 6). The peripheral blood of these patients was collected before and at different times after therapy commencement, and antigen-presenting dendritic cells (DCs) were then cultured. The DCs were enriched and cultured with Staphylococcus aureus Cowan strain-1 for 48 h to evaluate their capacity to produce nitrite.


RESULTS
One month after the start of bezafibrate therapy, the serum levels of alkaline phosphatase (P = 0.0005), gamma-glutamyl transpeptidase (P = 0.0006), total cholesterol (P = 0.0072), and immunoglobulin M (P = 0.0281) were decreased significantly compared to those before patients started bezafibrate therapy. The levels of nitrite produced by DCs decreased in all patients with PBC within 1 month of commencement of bezafibrate therapy. Moreover, decreased nitrite production by DCs was also seen when nitrite production was evaluated 1 year after the start of bezafibrate therapy.


CONCLUSIONS
This study reconfirms the therapeutic efficacy of bezafibrate in patients with PBC, including those with UDCA-resistant PBC. Downregulation of nitrite production by DCs may have some relationship with the therapeutic efficacy of bezafibrate; however, further study will be needed to clarify whether or not the antiinflammatory activity of bezafibrate is mediated through nitrite production.
Akbar
Sk Md Fazle
SM
Third Department of Intenal Medicine, Ehime University School of Medicine, Shigenobu-Cho, Ehime, 791-0295, Japan.
Furukawa
Shinya
S
Nakanishi
Seiji
S
Abe
Masanori
M
Horiike
Norio
N
Onji
Morikazu
M
D000328:Adult; D001629:Bezafibrate / Q000494:pharmacology / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D000960:Hypolipidemic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D008105:Liver Cirrhosis, Biliary / Q000188:drug therapy* / Q000503:physiopathology; D008111:Liver Function Tests; D008875:Middle Aged; D009573:Nitrites / Q000378:metabolism*
D000960:Hypolipidemic Agents; D009573:Nitrites; D001629:Bezafibrate