Doxorubicin in combination with other cytotoxic drugs has clinical advantages. However, doxorubicin-induced cardiotoxicity negatively impacts clinical utility and outcomes. Cardiotoxicity can result from increased oxidative stress or from a local cytochrome P450 mediated increase in 20-hydroxy-5, 8, 11, 14-eicosatetraenoic acid (20-HETE). Oleanolic acid (OA) is a natural pentacyclic triterpenoid with free radical scavenging, cardioprotective, and P450-mediated cyclooxygenase-upregulating properties. We investigated co-delivery of liposomal OA and doxorubicin in a HepG2 model of hepatocellular carcinoma (HCC). OA attenuated the cardiotoxicity induced by doxorubicin without compromising its anticancer activity. Apoptosis assays revealed that co-delivery of DOX and OA produced a synergistic anticancer effect. However, the drugs had antagonistic effects on cardiomyocytes. Female BALB/c nude mice treated with OA-and DOX-loaded liposomes (ODLs) exhibited reduced tumor growth, stable body weight, and stable organ indices. Reduced 20-HETE production suggested ODLs had limited cardiotoxicity. No changes in biochemical or histopathological markers were observed in mice treated with ODLs. Tailored co-delivery of OA and DOX may thus be an effective therapeutic strategy for treating HCC.
Exposure of Sprague-Dawley rats to a 60 Hz EMF at field strengths of up to 500 microT from day 6 of gestation to day 21 of lactation did not produce any detectable alterations in offspring spermatogenesis and fertility.
In this study, a method of metabolite profiling based on UPLC-QTOF/MS was developed to analyze Platycodon grandiflorum. In the optimal UPLC, various metabolites, including major platycosides, were separated well in 15 min. The metabolite extraction protocols were also optimized by selecting a solvent for use in the study, the ratio of solvent to sample and sonication time. This method was used to profile two different parts of P. grandiflorum, i.e., the roots of P. grandiflorum (PR) and the stems and leaves of P. grandiflorum (PS), in the positive and negative ion modes. As a result, PR and PS showed qualitatively and quantitatively different metabolite profiles. Furthermore, their metabolite compositions differed according to individual plant samples. These results indicate that the UPLC-QTOF/MS-based profiling method is a good tool to analyze various metabolites in P. grandiflorum. This metabolomics approach can also be applied to evaluate the overall quality of P. grandiflorum, as well as to discriminate the cultivars for the medicinal plant industry.
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