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J Transl Med. 2010 Mar 31;8:32. doi: 10.1186/1479-5876-8-32.

Effect of dipterinyl calcium pentahydrate on hepatitis B virus replication in transgenic mice.

Author information

1
SanRx Pharmaceuticals, Inc,, 603 Colima Street, La Jolla, California 92037-8032, USA. phil.moheno@sanrx.com

Abstract

BACKGROUND:

Dipterinyl calcium pentahydrate (DCP) has previously been shown to inhibit MDA-MB-231 human breast cancer xenographs in nude mice in a manner correlated with increases in plasma IL-12 and IL-4 concentrations, and decreases in plasma IL-6 levels. DCP also inhibits indoleamine 2,3-dioxygenase (IDO), an immuno-inhibitory enzyme, in human PBMCs (Peripheral Blood Mononuclear Cells).

METHODS:

In the present study, DCP was administered per os, once daily for 14 days to hepatitis B virus (HBV) transgenic mice at 23, 7.3, and 2.3 mg/(kg d). Multivariate stepwise regression and MANOVA analyses, by gender and treatment, of liver HBV DNA and RNA measures, liver core and serum HBe antigen assays, serum cytokine/chemokine profiles, and IDO metabolite measurements were performed.

RESULTS:

DCP caused a significant dose-response reduction of log liver HBV DNA as measured by PCR in the female HBV mice. The gender dependence of the anti-HBV DNA activity was explained by the DCP Effects Model (DCP-EM) (p = .001) which includes three serum biomarker changes caused by DCP: 1) decreased MCP-1; 2) decreased Kyn/Trp (an estimation of IDO activity); and 3) increased GM-CSF.

CONCLUSIONS:

Immunomodulation via IDO or TDO (tryptophan 2,3-dioxygenase) pathways, along with serum MCP-1 and GM-CSF are proposed to play roles in the anti-HBV mechanism of DCP based upon their coordinated modulation in the reduction of viral DNA replication in HBV mice.

PMID:
20356392
PMCID:
PMC2853516
DOI:
10.1186/1479-5876-8-32
[Indexed for MEDLINE]
Free PMC Article

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