1). Liver weight of NDEA alone treated rats increased significantly (p ≤ 0.05) at the end of the 20th week of exposure when compared with normal rats. But treatment with MEWF prevented the increase in liver weight in rats exposed to NDEA. MEWF alone treated rats did not show any significant changes when compared to normal control ( Table 1). NDEA treated rats showed significantly (p ≤ 0.05) elevated serum levels of AFP, ALP, LDH and bilirubin when compared to normal control. A significant (p ≤ 0.05) reduction was observed in serum Duvelisib in vivo markers in the animals treated with Silymarin (100 mg/kg), MEWF (100 mg/kg and 200 mg/kg) compared

to NDEA treated group ( Fig. 2). In morphology and morphometry evaluation, NDEA treated rat liver become very large in size and a large number of hepatic nodules were observed (Fig. 3). Administration of Silymarin and MEWF (100 mg/kg b.w, 200 mg/kg) showed significant reduction in the nodule incidence in NDEA induced hepatocarcinogenesis (Table 2). Tissue biochemical analysis showed a significant (p ≤ 0.05) reduction in GSH, CAT and increased levels of MDA in NDEA treated group compared to normal control. A significant (p ≤ 0.05) elevation in GSH, CAT and MDA were observed in animals treated with Silymarin (100 mg/kg), MEWF (100 mg/kg and 200 mg/kg) compared to NDEA treated group ( Table 3). In NDEA intoxicated rat tissue enlarged nuclei, hyperchromatism, scattered masses of necrotic tissues,

proliferating hepatocytes and mild congestion of sinusoids with central vein dilation were detected VE-822 chemical structure in histopathological studies. However, treatment with MEWF at a dose of 200 mg/kg showed almost normal architecture with normal hepatocytes and uniform secondly sinusoids (Fig. 4). In immunohistochemical

analysis NDEA intoxicated rat tissue showed localization of VEGF around periportal area (arrow heads). A significant down regulation of VEGF was spotted in MEWF at a dose of 200 mg/kg treated group (Fig. 5) The dose-dependent cytotoxic effect of MEWF on PLC/PRF/5 cells was evaluated by MTT assay. The cells were treated with 50 and 100 μg/ml of MEWF and the inhibition of cell proliferation was assessed after 12 h, 24 h, 48 h and 72 h. MEWF exerted cytotoxic effect on PLC/PRF/5 cells in a dose-dependent manner with percentage of cell inhibition values 12.4 ± 0.8, 23.1 ± 0.9, 44.4 ± 1.7 and 55.8 ± 2.2 for 50 μg/ml and 24.2 ± 1.3, 33.8 ± 1.2, 56.8 ± 2.0 and 65.3 ± 2.5 for 100 μg/ml after 12 h, 24 h, 48 h and 72 h respectively. 5-flourouracil, used as positive control, showed an inhibition of 26.8 ± 1.0, 36.2 ± 1.5, 59.2 ± 2.3 and 70.2 ± 2.8 for 50 μg/ml and 14.7 ± 1.1, 25.2 ± 0.8, 47.9 ± 1.8 and 59.1 ± 2.3 for 25 μg/ml after 12 h, 24 h, 48 h and 72 h respectively. Treatment with MEWF exhibited significant cytotoxic effect on PLC/PRF/5 cells (p ≤ 0.05) when compared to the cells treated alone with DMSO. The results were graphically expressed in Fig. 6.