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.

The behavioral response, dopamine metabolism, and characteristics of dopamine subtypes after developing the hyperglycemia were studied in the striata of rats. In animals developed hyperglycemia, the on-set and duration of cataleptic behavior responded to SCH 23390 injection was delayed and shortened, respectively. However, the cataleptic responses to spiperone occurred significantly earlier in on-set and prolonged in duration. Dopamine metabolites, dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA), were significantly reduced in the striata of hyperglycemic rats. However, level of DA was significantly increased. It is noted that the ratios of DOPAC and HVA to DA were decreased, suggesting decreased turnover of DA. The affinity of striatal D-1 receptors was significantly increased without changes in the number of binding sites, while the maximum binding number of D-2 receptors was significantly increased without affecting its affinity in the diabetic rats. These results indicate that the dopaminergic activity in the striata was altered in hyperglycemic rats. Furthermore, it suggests that the upregulation of dopamine receptors might be due to the decreased dopamine metabolism.