Antiviral effects of a niobium-substituted heteropolytungstate on hepatitis B virus-transgenic mice.

Abstract

To study the efficacy of a polyoxometalate, Cs2 K4 Na[SiW9 Nb3 O40 ]·H2 O, as an antiviral treatment in HBV transgenic mice. HBV transgenic mice were treated with Cs2 K4 Na[SiW9 Nb3 O40 ]·H2 O by intragastric administration. Adefovir and distilled water were administered as controls. Serum HBV DNA, liver HBV RNA levels were measured by quantitative RT-PCR. Serum HBsAg levels were measured by ELISA. The hepatitis B virus surface antigen (HBsAg) in liver cells was detected by immunohistochemistry (IHC). Pathological changes in the liver tissues were also observed by light and electron microscopy. Cs2 K4 Na[SiW9 Nb3 O40 ]·H2 O significantly decreased serum HBsAg and HBV DNA levels. Cs2 K4 Na[SiW9 Nb3 O40 ]·H2 O resulted in a 98% decrease in serum HBV DNA at 28 days, from 4.3 log10 copies/ml at baseline to 2.5 log10 copies/ml after treatment, and the inhibition rate of HBV DNA was higher than ADV at the same dose. The HBV replication levels in each group slightly increased at 7 days after withdrawal, but rebounded slightly more in the Cs2 K4 Na[SiW9 Nb3 O40 ]·H2 O treatment group compared to the H2 O control group (p < .05). There were no differences in HBV RNA levels. No significant differences were observed in the pathology, but there were decreased HBsAg levels in the Cs2 K4 Na[SiW9 Nb3 O40 ]·H2 O-treated group compared to the control group. The results demonstrated that Cs2 K4 Na[SiW9 Nb3 O40 ]·H2 O displayed potent anti-HBV activity in HBV transgenic mice and supported for future clinic study.