Liver cancer, predominantly hepatocellular carcinoma (HCC), represents a complex and fatal
malignancy driven primarily by oxidative stress and inflammation. The chemopreventive effect of
omega-3 on inflammatory markers and oxidative damage, caspase-3, antioxidant status and
histopathological alterations in hepatic tissue in N-nitrosodiethylamine (DEN)-induced HCC in male
rats was investigated. To induce HCC, rats were given DEN (200 mg/kg b.wt.,i.p) three times at a 15
day interval. 75 rats were divided into five equal groups. Control group, DEN group, DEN + ω3
protected group received omega-3 (270mg/kg b. wt/day) orally 4 weeks before DEN injection and
continued to 13 weeks, DEN + ω3 treated group firstly injected with DEN and orally treated with omega-
3 from the 8^th week till the end of the experiment (13^th week) and normal -ω3 group received omega-3.
Blood samples and liver tissues were collected at 13^th week. DEN-induced HCC significantly decreased
SOD and CAT activities in liver tissue. However, a marked increase in liver tissue L-MDA, DNA
fragmentation, caspase-3 and Nf-kB P65 and in serum AFP, IL-6 and TNF-α levels were observed in
DEN injected rats. Initiation of HCC was demonstrated by histopathological examination of hepatic
tissue in DEN injected group. Histopathological examination confirmed the pathological improvement
in the liver of rats in omega -3 protected and treated groups. In conclusion, omega-3 demonstrates antiinflammatory property by suppression of TNF-alpha and IL-6 due to inhibition of NF-kB p65 and exerts
its chemopreventive effect on liver carcinogenesis. These data suggest that omega-3 exhibited
significant protection against DEN-induced HCC, which might be related with the enhancement of the
antioxidant activity and the induction of apoptosis.