Inhibitory Effect of Selenium on N-Nitrosodiethylamine and Phenobarbital-Promoted Rat Liver Carcinogenesis.

J Trace Elements Exper Med

Selvedhiran

Singh

et al. 2003

As part of a substantial effort to curtail the adverse health effects posed by hepatoma, studies have been conducted to elucidate the possible mechanism for the anticarcinogenic action of sodium selenite against N-nitrosodiethylamine-induced hepatoma. Several investigations recognize selenium as potent antioxidant, as well as an anticarcinogen, in both animal and human systems. Sodium selenite was administered to Wistar rats bearing hepatoma induced by N-nitrosodiethylamine to study the alterations in the concentration of lipid profiles and in activities of some lipid-metabolizing enzymes. Control and tumor-bearing animals were fed 4 ppm of sodium selenite before initiation or during initiation and/or during promotion phases of carcinogenesis. Hepatic total cholesterol, free cholesterol, triglycerides, free fatty acids, and phospholipids were significantly lowered, whereas cholesterol esters was greater because of selenite administration in N-nitrosodiethylamine-induced tumor-bearing rats. Total lipase, lipoprotein lipase, lecithin: cholesterol acyl transferase, and cholesterol ester synthetase registered greater activities in hepatoma of selenite administered rats with tumor whereas the activity of cholesterol ester hydrolase in hepatoma-bearing animals was lower as a result of selenite administration. These observations clearly indicate the effect of selenite in correcting the abnormalities of lipid metabolism in tumor-induced animals. Previous evidence from this laboratory and present observations it can be concluded that the anticancer property of selenite my also be by its strong hypolipidemic capacity in vivo system.

Section: Discussionsupporting

confidence: 64%

Section: Discussionmentioning

confidence: 53%

Effect of sodium selenite on lipids and lipid‐metabolizing enzymes in N‐nitrosodiethylamine‐induced hepatoma‐bearing rats

J Trace Elements Exper Med

Selvedhiran

Singh

et al. 2003

“…either before initiation or during initiation and/or during promotion can significantly reduce cancer incidence and morbidity. 12 At the same concentration it did not affect the control animals. 12 The purpose of the present study is to demonstrate the protective response of sodium selenite by modulating marker enzyme changes in rat hepatocarcinogenesis induced by N-nitrosodiethylamine.…”

Section: Introductionmentioning

confidence: 84%

“…12 At the same concentration it did not affect the control animals. 12 The purpose of the present study is to demonstrate the protective response of sodium selenite by modulating marker enzyme changes in rat hepatocarcinogenesis induced by N-nitrosodiethylamine. This may help us further to understand the additive inhibitory effect of sodium selenite on the biochemistry of DEN-induced rat liver carcinogenesis.…”

Section: Introductionmentioning

confidence: 84%

Sodium selenite modulates tumour marker indices in N‐nitrosodiethylamine‐initiated and phenobarbital‐promoted rat liver carcinogenesis

Cell Biochemistry & Function

Sakthisekaran

2003

The effect of sodium selenite (Se) was investigated against two-stage rat liver carcinogenesis initiated by a single intraperitoneal injection of N-nitrosodiethylamine (DEN, 200 mg kg(-1) i.p.) followed by promotion with phenobarbital (PB, 0.05%) in a basal diet. Se (4 p.p.m.) was administered per os daily throughout the entire experiment, before the initiation, or during the promotion stage. The plasma, liver (hepatoma and surrounding tissue) and kidney tissue were investigated biochemically for lactate dehydrogenase, aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase and 5'-nucleotidase. These enzyme activities were increased (p < 0.001) in plasma of hepatoma-bearing rats compared with normal control rats. The elevation of these enzyme activities in plasma was indicative of the persistent deteriorating effect of DEN in cancer-bearing animals. Aminotransferase levels were decreased in hepatoma and surrounding liver tissue, whereas lactate dehydrogenase, alkaline phosphatase and 5'-nucleotidase were increased in the cancer condition. These enzyme activities were reversed to near normal control values in animals treated with Se. It is apparent that the beneficial effect of Se is primarily exerted on the initiation phase and secondarily during the promotion stage of DEN-initiated rat liver carcinogenesis. The analysis of marker enzyme activities taken together with our previous findings clearly indicates the antitumour efficacy of sodium selenite on DEN-induced hepatoma animals.

“…Previous studies from our laboratory had shown that an increased concentration of Se in different organs of tumour-bearing rats is not directly proportional to the chemopreventive effectiveness of this compound. 11 However the chemopreventive/chemotherapeutic effect of Se is not ruled out. A striking observation of the present study was that Se supplementation before initiation, selenite against hepatoma with reference to non-enzymic antioxidants 269 during initiation and during promotion stages, demonstrated a pronounced effect in inhibiting the appearance of hepatic nodules of more than 3 mm in size from 41.9% (group 2) to 12.7% (group 3), 23.4% (group 5) and 27.8% (group 7) respectively.…”

Section: Discussionmentioning

confidence: 99%

Antioxidant‐associated chemoprevention by sodium selenite in N‐nitrosodiethylamine‐induced and phenobarbital‐promoted hepatocarcinogenesis in rats

Cell Biochemistry & Function

Babu

Ebrahim

et al. 2004

The anticarcinogenic/antioxidant potential of sodium selenite (Se), a micronutrient, was evaluated on liver tumourigenesis induced by N-nitrosodiethylamine (DEN) and promoted by phenobarbital (PB; 0.05% in diet). Male, albino rats of the Wistar strain were exposed intravenously to a single dose of DEN (200 mg x kg(-1) body weight). Se (4 ppm in drinking water) was supplemented before initiation, or during initiation and/or during the promotion period of carcinogenesis. At the end of 16 weeks (after DEN administration) nodular incidence, the total number of nodules and non-enzymic antioxidants such as vitamin E, vitamin C, total thiol, protein thiol and non-protein thiol contents were measured in hepatoma, surrounding tissue and kidney tissue of control and experimental groups. In hepatoma-bearing animals the above biochemical changes were decreased when compared with normal control animals. On Se treatment throughout the study, (20 weeks) the above biochemical changes reverted to normal levels. Pre- and post-treatment with Se also shows a tendency to reverse the above changes. The results indicate that prior application of Se significantly reverses the adverse changes produced during the tumourigenesis. Furthermore, prior applications of Se significantly reduced the cumulative number of tumours per tumour-bearing animals. The present study reveals the antitumour potential of Se against DEN-induced liver carcinogenesis.