NMR-spectroscopy-based metabonomic approach to the analysis of Bay41-4109, a novel anti-HBV compound, induced hepatotoxicity in rats

Shi, Changhong; Wu, Cathy; Cao, Amin; Sheng, He-Zhang; Yan, Xianzhong; Ming-yang, Liao

doi:10.1016/j.toxlet.2007.07.010

Cited by 49 publications

(42 citation statements)

References 18 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…[28][29][30] It was performed in this study to assess the biological impact of SWCNT injection on liver metabolism as a general index of toxicity. HR-MAS 1 H NMR spectroscopy of intact tissue enables the simultaneous measurement of both lipids and low molecular weight metabolites, which is important in a toxicological diagnosis.…”

Section: Hr-masmentioning

confidence: 99%

In vivo biodistribution and biological impact of injected carbon nanotubes using magnetic resonance techniques

Faraj¹,

Fauvelle²,

Luciani³

et al. 2011

IJN

View full text Add to dashboard Cite

International audienceSingle-walled carbon nanotubes (SWCNT) hold promise for applications as contrast agents and target delivery carriers in the field of nanomedicine. When administered in vivo, their biodistribution and pharmacological profile needs to be fully characterized. The tissue distribution of carbon nanotubes and their potential impact on metabolism depend on their shape, coating, and metallic impurities. Because standard radiolabeled or fluorescentlylabeled pharmaceuticals are not well suited for long-term in vivo follow-up of carbon nanotubes, alternative methods are required

show abstract

Section: Hr-masmentioning

confidence: 99%

In vivo biodistribution and biological impact of injected carbon nanotubes using magnetic resonance techniques

Faraj¹,

Fauvelle²,

Luciani³

et al. 2011

IJN

View full text Add to dashboard Cite

show abstract

“…BAY 41-4109 was shown to partially inhibit the virus replication cycle in HBV transgenic mice (24) and in Alb-uPA/ SCID mice (25). HBV BAY 41-4109 was also effective against lamivudine-and adefovir-resistant mutants (22,26) but was hepatotoxic at high doses in rats (27). To build upon these findings, a series of BAY 41-4109 analogs were made, and the analog GLS4 (28) was shown to have potent antiviral activity in vitro in HepG2.2.15 cells (26).…”

mentioning

confidence: 99%

Preclinical Characterization of GLS4, an Inhibitor of Hepatitis B Virus Core Particle Assembly

Liu

Zhang

et al. 2013

Antimicrob Agents Chemother

106

View full text Add to dashboard Cite

Hepatitis B virus (HBV)-associated chronic liver diseases are treated with nucleoside analogs that target the virus polymerase. While these analogs are potent, drugs are needed to target other virus-encoded gene products to better block the virus replication cycle and chronic liver disease. This work further characterized GLS4 and compared it to the related BAY 41-4109, both of which trigger aberrant HBV core particle assembly, where the virus replication cycle occurs. This was done in HepAD38 cells, which replicate HBV to high levels. In vitro, GLS4 was significantly less toxic for primary human hepatocytes (P < 0.01 up to 100 M), inhibited virus accumulation in the supernantant of HepAD38 cells (P < 0.02 up to 100 nM), inhibited HBV replicative forms in the liver with a significantly lower 50% effective concentration (EC 50 ) (P < 0.02), and more strongly inhibited core gene expression (P < 0.001 at 100 to 200 nM) compared to BAY 41-4109. In vivo characterization was performed in nude mice inoculated with HepAD38 cells, which grew out as tumors, resulting in viremia. Treatment of mice with GLS4 and BAY 41-4109 showed strong and sustained suppression of virus DNA to about the same extents both during and after treatment. Both drugs reduced the levels of intracellular core antigen in the tumors. Alanine aminotransferase levels were normal. Tumor and total body weights were not affected by treatment. Thus, GLS4 was as potent as the prototype, BAY 41-4109, and was superior to lamivudine, in that there was little virus relapse after the end of treatment and no indication of toxicity.

show abstract

“…Since 1999, metabonomics has been widely used to assess the pharmacological safety and toxicological mechanism of drugs in animal models. (Shi et al, 2007;Wei et al, 2008).…”

Section: Introductionmentioning

confidence: 99%

Metabolic analysis of the effect of rheum on a taurocholate-induced acute pancreatitis rat model

Chen

Shen

Yang

et al. 2017

Braz. J. Pharm. Sci.

View full text Add to dashboard Cite

The effects of rheum on serum parameters in a taurocholate-induced acute pancreatitis (AP) rat model were investigated using pathological and biochemical tests, and a proton nuclear magnetic resonance ( 1 H NMR)-based metabonomic strategy. Healthy rats and rats with AP were either treated with rheum (7.5% at a dose of 1.5 g/kg) or left untreated. Serum samples were collected from the AP and rheum-treated groups at 6, 12, and 24 h after treatment. The effect of rheum on pathological changes in the pancreatic was investigated to validate the AP model. We obtained 1 H NMR spectra and analyzed the results using the partial least squares discriminant method. The results of the pathological and metabolic analyses revealed an amelioration of multiple metabolic abnormalities and an increase in the aerobic respiration ratio after treatment, compared with the AP groups. These results were attributed to improvements in energy supply and the elimination of metabolic products. The study also promoted NMR-based metabonomic analysis as a feasible method of assessing traditional Chinese drugs.

show abstract

NMR-spectroscopy-based metabonomic approach to the analysis of Bay41-4109, a novel anti-HBV compound, induced hepatotoxicity in rats

Cited by 49 publications

References 18 publications

In vivo biodistribution and biological impact of injected carbon nanotubes using magnetic resonance techniques

In vivo biodistribution and biological impact of injected carbon nanotubes using magnetic resonance techniques

Preclinical Characterization of GLS4, an Inhibitor of Hepatitis B Virus Core Particle Assembly

Metabolic analysis of the effect of rheum on a taurocholate-induced acute pancreatitis rat model

Contact Info

Product

Resources

About