Abstract
Nitrosamine compounds are known hepatic carcinogens. This study was designed to study the efficacy of dietary supplementation with blueberries (BB) on diethylnitrosamine (DEN)-initiated hepatocarcinogenesis in male wistar rats. Rats were divided into three groups. The first group served as normal control group, the second group received DEN at a dose of 10 mg/kg body weight five times a week for 15 weeks. The third one received DEN as in DEN-treated group simultaneously with 4% BB-supplemented diet. The results showed that BB caused significant decrease in the elevated serum levels of α-fetoprotein (AFP), homocysteine (Hcy) along with levels of glutathione(GSH), deoxyribonucleic acid (DNA), ribonucleic acid (RNA)and activity of glutathione reductase (GR) in liver. Normalization of elevated 2-macroglobulin (2M) and total antioxidant capacity (TAC) levels in serum, hepatic Glutathione-S-transferase (GST), glutathione peroxidase (GPx) activities and liver weight was achieved whereas body weight was significantly decreased. Moreover, no significant change was observed in elevated relative liver weight, hepatic glucose-6-P-dehydrogenase (G6PD), lactate dehydrogenase (LDH) along with serum aminotransferases, alkaline phosphatase (ALP) and ɤ -glutamyltransferase (ɤ-GT) activities. Significant increase in reduced hepatic activity of xanthine oxidase (XO) was achieved and histopathological damage was minimized in BB-treated group. It is suggested that BB suppress DEN-induced hepatocarcinogenesis and could be developed as a promising chemoprotective natural supplement for liver cancer.
Highlights
Diethylnitrosamine (DEN) is an established hepatocarcinogen in rats (Hussein et al, 2015)
No significant change was observed in body weight in the DEN-treated group whereas increased liver weight and relative liver weight was shown as compared with the control group
BB supplementation resulted in normalization of serum α2M and significant decrease of agents. Serum α- fetoprotein (AFP) and Hcy levels whereas no significant change in activities of ALT, AST, alkaline phosphatase (ALP) and ɤ-GT was observed as compared with DEN group
Summary
Diethylnitrosamine (DEN) is an established hepatocarcinogen in rats (Hussein et al, 2015). Diethylnitrosamine (DEN), a hepatocarcinogen, is known to cause perturbations in the nuclear enzymes involved in deoxyribonucleic acid (DNA) repair/replication and is normally used as a carcinogen to induce liver cancer in animal models (Kanda et al, 2015). Epidemiologic and clinical studies have shown that dietary intakes of blueberries (BB) may have potential to reduce various types of cancers (Wang et al, 2013; Coban et al, 2014), including liver cancer (Kumar, 2015). Yi et al (2006) have found that phenolic compounds in blueberries could inhibit HepG2 liver cancer cell population growth and induce apoptosis. The present study aims to carry out a systematic investigation of the protective influences of blueberries against DEN-induced hepatocarcinogenesis by analyzing serum αfetoprotein, α2-macroglobulin and homocysteine levels along with the non-enzymatic and enzymatic anti-oxidants as biochemical end points of chemoprevention
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