NUTRITIONSupplementation of selenium reduces chemical hepatocarcinogenesis in male Sprague-Dawley rats
Introduction
Hepatocellular carcinoma (HCC) is common in the developing countries such as China, Korea and Africa [1]. Although, it is low in the developed countries, recent study of But et al. [2] showed that HCC is increasing in the developed countries such as USA, UK and France. Chronic infection with hepatitis B and C are the major risk factors for HCC worldwide. Other factors that contribute to the formation of HCC include exposure to aflatoxin, alcohol abuse, hemochromatosis, fatty liver disease and androgenic steroid use [3].
Selenium is a naturally occurring mineral element found mostly in soils and rocks. It functions as an essential micronutrient at a level of about 0.1 mg/kg in the animal diet, and selenium becomes toxic at levels of 8–10 mg/kg [4]. It is an essential component of glutathione peroxidase and thioredoxin reductase [5]. Experimental, epidemiological and clinical studies have shown that selenium can protect against the development of certain cancers [6], [7], [8]. A variety of clinical studies from different countries have shown that supplementation of selenium for a certain period of time reduces the incidence of certain cancers [6], [9], [10], [11]. In 1986, Combs and Combs [12] estimated that in more than 100 animal studies for which tumor or pre-neoplastic endpoints had been measured, two thirds of these studies showed reductions in the tumor incidence with half showing reductions of 50% or more. They observed that only a few studies have found selenium to be ineffective. In addition, other researchers have reported the chemoprevention effect of selenium against certain cancers in rodents [7], [13], [14]. Numerous epidemiological studies have shown that cancer patients have lowered selenium level, on average, than healthy controls [8], [15], [16], [17]. To date, the use of selenium in preventing or treating cancers is limited and controversial. Thus, the purpose of this study was to investigate the macro and microscopic effects of pre and post-selenium treatments on chemically induced liver cancer in rats.
Section snippets
Chemicals
Sodium selenite, diethyl nitrosamine (DEN) and 2-acetylaminofluorene (2-AAF) were obtained from Sigma Chemical Co., Germany. Hematoxylin, eosin and silver nitrate from BDH, UK. Paraffin waxes, xylene, denatured ethyl alcohol and formaldehyde from MERCK, Germany.
Animals and diet
Male Sprague-Dawley rats (120–190 g) (6–8 weeks) were obtained from the Laboratory Animal Resource Unit, Faculty of Medicine, Universiti Kebangsaan Malaysia, Kuala Lumpur, Malaysia. They were housed in plastic cages (3–4 rats per cage)
Results
During the entire period of the study, no obvious symptoms or changes in hair, nails or skin were seen among all the groups of rats. Water intakes for all groups were 10.5–12.5 mL per 100 g body weight. However, food intakes differed; treated groups (2, 3 and 5) had an average of 5.30–7.10 g per 100 g body weight whereas untreated groups (1, 4 and 6) had an average of 9.20–11.0 g per 100 g body weight. For unknown reasons, 3 rats died before the end of the study, one from Group 3 (week 4), Group 4
Discussion
The results of this study show that dietary administration of sodium selenite (4 mg/kg) has reduced the extent of liver cancer on chemically induced hepatocarcinogenesis in rats. An interesting finding in this study was that dietary selenium concentration (0.2 mg/kg, which is at the recommended range level) had no effect on the numbers and sizes of liver nodules as seen in the positive control. This might indicate that a high dose of selenium is required to inhibit or slow down the formation of
Acknowledgments
This study was supported by grant from the Ministry of Science, Technology and Innovation (MOSTI), Malaysia (no 05-01-02-SF0014).
References (42)
- et al.
The antioxidant role f selenium and seleno-compounds
Biomed Pharmacother
(2003) - et al.
Micronuclei and carcinogen DNA adducts as intermediate end points in nutrient intervention trial of precancerous lesions in the oral cavity
Eur J Cancer B Oral Oncol
(1995) - et al.
Effect of dietary selenite on N-nitrosodiethylamine induced and Phenobarbital promoted multistage hepatocarcinogenesis in rats; reflection in some minerals
Biomedicine and Pharmacotherapy
(2003) - et al.
A report of high dose selenium supplementation: response and toxicities
J Trace Elem Med Biol
(2004) - et al.
Endemic selenium intoxication of humans in China
Am J Clin Nutr
(1983) Clonal adaptation during carcinogenesis
Biochem Pharmacol
(1990)- et al.
Global cancer statistics, 2002
CA. Cancer J Clin
(2005) - et al.
Natural history of hepatitis related hepatocellular carcinoma
World J Gastroenterol
(2008) Trace element concentration in primar liver cancers – a systematic review
Biol Trace Res
(2007)- et al.
Toxicological effects of sodium selenite in Sprague-Dawley rats
J Toxicol Environ Health
(1981)
The nutritional prevention of cancer with selenium 1983–1993: a randomized clinical trial
JAMA
Selenium prevents tumor development in rat module for chemical carcinogenesis
Carcinogenesis
Serum selenium contents and the risk of cancer
Gan To Kagaku Ryoho
Protective role of selenium against hepatitis B virus and primary liver cancer in Qidong
Biol Trace Elem Res
Selenium and cancer
Effects of dietary selenium hepatic and renal tumorigenesis induced in rats by diethyl nitrosamine
Hepatology
Regional variation of cancer mortality incidence and its relation to selenium levels in China
Biol Trace Elem Res
Serum selenium and subsequent risk of cancer among Finnish men and women
J Nat Cancer Inst
The Linxian trials: mortality rates by vitamin–mineral intervention group
Am J Clin Nutr
New principle for the analysis of chemical analysis
Nature
Cited by (20)
The Regulation of Pathways of Inflammation and Resolution in Immune Cells and Cancer Stem Cells by Selenium
2017, Advances in Cancer ResearchCitation Excerpt :On the other hand, constitutive activation of the NF-κB pathway allows LSCs to evade mechanisms of apoptosis (Bosman, Schuringa, & Vellenga, 2016; Konopleva & Jordan, 2011; Zhou, Ching, & Chng, 2015). As part of the intrinsic pathway, selenium is shown to suppress activation of NF-κB in murine model of esophageal carcinogenesis (Yang, Jia, Chen, Yang, & Li, 2012), human prostate cancer cells (Christensen, Nartey, Hada, Legg, & Barzee, 2007), during hepatocarcinogenesis (Alwahaibi, Mohamed, & Alhamadani, 2010) and in colorectal cancer (Méplan & Hesketh, 2012; Ravasco et al., 2010). While it is known that LSCs can also endogenously produce CyPGs in response to supplementation with selenium, albeit at much lower concentration than macrophages, these CyPGs can diffuse into cells to bind to intracellular receptors such as PPARγ.
Long-term study of ovine pulmonary adenocarcinogenesis in sheep with marginal vs. sufficient nutritional selenium supply: Results from computed tomography, pathology, immunohistochemistry, JSRV-PCR and lung biochemistry
2013, Journal of Trace Elements in Medicine and BiologyCitation Excerpt :Research on the influence of nutritional factors on cancer insertion and progression is currently of increasing interest due to the potential use of functional food approaches for prevention and therapy. Several studies suggested a protective effect of selenium (Se) on cancer incidence [2,3], although it might be restricted to individuals entering the study with lower baseline plasma Se concentrations [4,5]. Recently, a meta-analysis study summarised that most investigations suggested moderate but not very high Se levels for reduced lung cancer risk [5].
Impact of zinc, selenium and lycopene on capsaicin induced mutagenicity and oxidative damage in mice
2013, Journal of Trace Elements in Medicine and BiologyCitation Excerpt :Preneoplastic and neoplastic lesions in rat liver were reduced on supplementation of diet with sodium selenite (5 μg/ml/100 g) for periods ranging from 1 day to several weeks [50]. Alwahaibi et al. observed that sodium selenite (4 mg/kg) could avert hepatocellular carcinoma by an antioxidant action and improve DNA repair [51]. A 4-fold decline in the extent of lipid peroxidation was observed with the combination.
Preventive effect of Metformin against N-nitrosodiethylamine-initiated hepatocellular carcinoma in rats
2012, Saudi Pharmaceutical JournalCitation Excerpt :The protocol was approved by the Institutional Animal Ethics Committee (IAEC) as per the guidance of the Committee for the Purpose of Control and Supervision of Experiments on Animals (CPCSEA); Ministry of Social Justice and Empowerment, Government of India. Liver cancer was induced by a carcinogenic dose of 200 mg/kg body weight, I.P. DENA when associated with fasting/refeeding (Alwahaibi et al., 2010; Gonul et al., 1996; Muzio et al., 1999; Xu-yinga et al., 2009). The rats were acclimatized and randomly divided into five groups each having 6 rats for a 16 week study.