Elevated plasma concentrations of soluble VEGFA isoforms are associated with poor prognosis in parallel with improved response to treatment with the anti-VEGFA antibody bevacizumab. To uncover the underlying mechanism to these observations, we administered anti-VEGFA therapy to mice bearing luminescent mouse fibrosarcomas expressing single VEGFA isoforms or their wild-type counterparts expressing all isoforms (fs120, fs164, fs188, or fsWT). Expression of the more soluble isoforms conferred an advantage for lung metastasis from subcutaneous tumors (fs120/164 vs. fs188/WT); fs120 cells also produced more lung colonies than fs188 cells when injected intravenously. Metastasis from subcutaneous fs120 tumors was more sensitive than fs188 to treatment with the anti-VEGFA antibody B20-4.1.1. Despite elevated plasma levels of VEGFA in fs120 tumor-bearing mice and a dependence on VEGF receptor 1 activity for metastasis to the lung, B20-4

Objective: Pregnane X receptor (PXR), member of nuclear receptor family, an integral component of the body defence mechanism against chemical insult are expressed in the liver, gastrointestinal system & lungs. Some studies have shown that the lovastatin is pregnane X receptor (PXR) activation effect. Methods: In the present study the hepatoprotective effect of lovastatin was investigated against lithocholic acid induced liver toxicity. Liver markers in serum and antioxidant enzymes in liver tissue were assessed by using standard procedures. Results: The level of liver marker (such as SGOT & SGPT) and bilirubin were increased significantly (p<0.05) and antioxidant enzyme (i.e. SOD, GSH and CAT) were significantly (p<0.05) decrease in lithocholic acid treated groups as compared to control group. Lovastatin at doses of 0.1, 0.2, 0.3 mg/kg showed significantly (p<0.05) decrease in the levels of liver marker (SGOT & SGPT) and bilirubin as compared to the positive control group in both pre & post treated models. The antioxidant enzymes such as Superoxide dismutase (SOD), Glutathione (GSH) and Catalase (CAT) content in liver tissue were significantly (p<0.05) increase after administration of lovastatin at dose dependent manner in both pre & post treated models. Conclusions: The results of the present study indicates that under the present experimental conditions, lovastatin showed hepatoprotective abilities against lithocholic acid induced hepatotoxicity in albino rat. Keywords: Hepatoprotection, lovastatin, Lithocholic Acid, Pregnane X Receptor