Effects of Amantadine and Biphenyl Dimethyl Dicarboxylate on Hepatitis B Virus in Hepatitis B Virus Replication Mice_Journal of Biomedical Engineering

Authors：

 LIUFengjun ¹ , JIANGZhi ² , ZHOUQiaoling ³ , YUYi ¹ , MENGHuanghua ¹ , SHIYao ¹

1. Department of Infectious Diseases, Affiliate Hospital, North Sichuan Medical College, Nanchong 637000, China;
2. Department of Emergency, Affiliate Hospital, North Sichuan Medical College, Nanchong 637000, China;
3. Center of Infectious Diseases;Division of Molecular Biology of Infectious Diseases, National Key Laboratory of Biotherapy(Sichuan University;

Corresponding author：

LIUFengjun, Email: lfj116@126.com

Keywords：

amantadine; biphenyl dimethyl dicarboxylate; hepatitis B virus; animal model; hydrodynamics-based in vivo transfection

DOI：

10.7507/1001-5515.20140075

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This study sought to investigate the in vivo antiviral effect of amantadine (AM) and biphenyl dimethyl dicarboxylate (DDB) on hepatitis B virus (HBV) in HBV replication mice. HBV replication-competent plasmid was transferred into male BALB/c mice by using hydrodynamics-based in vivo transfection procedure to develop HBV replication mouse model. The model mice were matched by body weigh, age and serum levels of hepatitis B e antigen (HBeAg) and were divided into four groups:AM group, DDB group, AM+DDB group and NS group, with the last one as control, and the mice of each group were administered corresponding agent orally twice a day, in a medication course lasting 3 d. On the third day, the mice were sacrificed 4-6 h after the last oral intake. HBV DNA replication intermediates in liver were analyzed by Southern blot hybridization. The serum hepatitis B surface antigen (HBsAg) and HBeAg were detected by enzyme linked immunosorbent assay (ELISA). Compared to the animals in the control group, HBV DNA replication intermediates in liver and HBsAg and HBeAg in serum from the AM and AM plus DDB group of mice decreased, and there was no difference between these two groups of mice. The levels of HBV DNA intermediate from liver and the serum HBsAg and HBeAg between the control and DDB group, however, were not obviously different. In conclusion, the inhibition effect of AM on HBV was detected, but treatment with DDB for 3 days did not influence the viral replication and expression of HBV in the HBV replication mice.

Citation： LIUFengjun, JIANGZhi, ZHOUQiaoling, YUYi, MENGHuanghua, SHIYao. Effects of Amantadine and Biphenyl Dimethyl Dicarboxylate on Hepatitis B Virus in Hepatitis B Virus Replication Mice. Journal of Biomedical Engineering, 2014, 31(2): 400-404. doi: 10.7507/1001-5515.20140075 Copy

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11.	LIU F J,LIU L,HE F,et al.Establishment and primary application of a mouse model with hepatitis B virus replication[J].World J Gastroenterol,2007,13(40):5324-5330.
12.	刘凤君,刘丽,蒋智,等.恩替卡韦抑制乙型肝炎病毒复制型小鼠体内病毒的复制[J].基础医学与临床,2009,29(10):1017-1020.
13.	GAO Z,LIU F J,LEI J,et al.Application value of HBV replication mouse model in HBV study[J].World J Gastroenterol,2010,16(16):1979-1985.
14.	LIU F J,CHEN E Q,ZHOU Q L,et al.Functional characterization of interferon regulatory element of HBV genome in vivo[J].Indian J Virol,2012,23(3):278-285.
15.	DELTENRE P,HENRION J,CANVA V,et al.Evaluation of amantadine in chronic hepatitis C:a meta-analysis[J].J Hepatol,2004,41(3):462-473.
16.	MANGIA A,LEANDRO G,HELBLING B,et al.Combination therapy with amantadine and interferon in naïve patients with chronic hepatitis C:meta-analysis of individual patient data from six clinical trials[J].J Hepatol,2004,40(3):478-483.
17.	KRONENBERGER B,BERG T,HERRMANN E,et al.Efficacy of amantadine on quality of life in patients with chronic hepatitis C treated with interferon-alpha and ribavirin:results from a randomized,placebo-controlled,double-blind trial[J].Eur J Gastroenterol Hepatol,2007,19(8):639-646.

1. BRILLANTI S,LEVANTESI F,MASI L,et al.Triple antiviral therapy as a new option for patients with interferon nonresponsive chronic hepatitis C[J].Hepatology,2000,32(3):630-634.
2. BERG T,KRONENBERGER B,HINRICHSEN H,et al.Triple therapy with amantadine in treatment-naive patients with chronic hepatitis C:a placebo-controlled trial[J].Hepatology,2003,37(6):1359-1367.
3. TEUBER G,PASCU M,BERG T,et al.Randomized,controlled trial with IFN-alpha combined with ribavirin with and without amantadine sulphate in non-responders with chronic hepatitis C[J].J Hepatol,2003,39(4):606-613.
4. FARGIO B,BORZIO M,MARASCHI A,et al.T riple antiviral therapy in HCV positive patients who failed prior combination therapy[J].World J Gastroenterol,2006,12(33):5293-5330.
5. KIM J H,MUN Y J,CHUN H J,et al.Effect of biphenyl dimethyl dicarboxylate on the humoral immunosuppression by ethanol[J].Int J Immunopharmacol,2000,22(11):905-913.
6. KIM J H,KANG T W.Effect of biphenyl dimethyl dicarboxylate on the cellular and nonspecific immunosuppressions by ketoconazole in mice[J].Arch Pharm Res,1999,22(3):255-261.
7. JOO S S,LEE D I.The potential anti-HBV effect of amantadine in combination with ursodeoxycholic acid and biphenyl dimethyl dicarboxylate in HepG22.2.15 cells[J].Arch Pharm Res,2005,28(4):451-457.
8. JOO S S,WON J W,KIM M J,et al.Interferon signal transduction of biphenyl dimethyl dicarboxylate/amantadine and anti-HBV activity in HepG22.2.15[J].Arch Pharm Res,2006,29(5):405-411.
9. 崔速南,汪明明,范桂玲.大剂量联苯双酯抗乙型肝炎病毒疗效的临床观察[J].中华医学杂志,2002,82(8):538-540.
10. 崔速南,王兆红,李新立,等.长期服用联苯双酯治疗慢性乙型肝炎的病毒学疗效探讨[J].中西医结合肝病杂志,2002,12(3):144-146.
11. LIU F J,LIU L,HE F,et al.Establishment and primary application of a mouse model with hepatitis B virus replication[J].World J Gastroenterol,2007,13(40):5324-5330.
12. 刘凤君,刘丽,蒋智,等.恩替卡韦抑制乙型肝炎病毒复制型小鼠体内病毒的复制[J].基础医学与临床,2009,29(10):1017-1020.
13. GAO Z,LIU F J,LEI J,et al.Application value of HBV replication mouse model in HBV study[J].World J Gastroenterol,2010,16(16):1979-1985.
14. LIU F J,CHEN E Q,ZHOU Q L,et al.Functional characterization of interferon regulatory element of HBV genome in vivo[J].Indian J Virol,2012,23(3):278-285.
15. DELTENRE P,HENRION J,CANVA V,et al.Evaluation of amantadine in chronic hepatitis C:a meta-analysis[J].J Hepatol,2004,41(3):462-473.
16. MANGIA A,LEANDRO G,HELBLING B,et al.Combination therapy with amantadine and interferon in naïve patients with chronic hepatitis C:meta-analysis of individual patient data from six clinical trials[J].J Hepatol,2004,40(3):478-483.
17. KRONENBERGER B,BERG T,HERRMANN E,et al.Efficacy of amantadine on quality of life in patients with chronic hepatitis C treated with interferon-alpha and ribavirin:results from a randomized,placebo-controlled,double-blind trial[J].Eur J Gastroenterol Hepatol,2007,19(8):639-646.

Journal of Biomedical Engineering

Effects of Amantadine and Biphenyl Dimethyl Dicarboxylate on Hepatitis B Virus in Hepatitis B Virus Replication Mice

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