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Inhibition of in vitro HBsAg production by amphotericin B and ketoconazole
Abstract:
The effects of amphotericin B, ketoconazole, and adenine arabinoside on production of hepatitis B surface antigen (HBsAg) particles by the human hepatoma cell line PLC/PRF/5 were examined. In addition, the effects of these drugs on cellular protein synthesis were determined. These drugs caused a dose-dependent decrease in HBsAg production that was paralleled by a decrease in cellular protein synthesis. Ketoconazole was the most active of these drugs and the most specific, causing a 72% reduction in HBsAg production with only a 38% reduction in protein synthesis. These data suggest that further studies evaluating ketoconazole for the treatment of chronic hepatitis B virus infection in animals are warranted.
Insights
Antiviral drugs, including ketoconazole, reduced hepatitis B surface antigen (HBsAg) production in a human liver cancer cell line. Ketoconazole showed the most promise for treating chronic hepatitis B virus infection.
Area of Science:
- Hepatology
- Virology
- Pharmacology
Background:
- Chronic hepatitis B virus (HBV) infection remains a significant global health concern.
- Current treatments have limitations, necessitating the exploration of novel therapeutic agents.
Purpose of the Study:
- To investigate the impact of amphotericin B, ketoconazole, and adenine arabinoside on hepatitis B surface antigen (HBsAg) production.
- To assess the effects of these drugs on cellular protein synthesis in a human hepatoma cell line.
Main Methods:
- Utilized the human hepatoma cell line PLC/PRF/5.
- Administered varying doses of amphotericin B, ketoconazole, and adenine arabinoside.
- Quantified HBsAg particle production and cellular protein synthesis.
Main Results:
- All tested drugs demonstrated a dose-dependent reduction in HBsAg production.
- This reduction in HBsAg was accompanied by a decrease in overall cellular protein synthesis.
- Ketoconazole exhibited the greatest efficacy and specificity, reducing HBsAg by 72% with only a 38% impact on protein synthesis.
Conclusions:
- Ketoconazole shows potential as a specific inhibitor of HBsAg production.
- Further preclinical studies in animal models are warranted to evaluate ketoconazole for chronic HBV infection treatment.