Protective role of chickpea seed coat fibre on N-nitrosodiethylamine-induced toxicity in hypercholesterolemic rats

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Abstract

N-nitrosodiethylamine (NDEA) is one of the important carcinogenic nitrosamines frequently present in human environment and food chain that poses a significant human health hazard. This study was planned to investigate the protective role of dietary fibre on NDEA-induced toxicity in hypercholesterolemic rats. Oral administration of NDEA at a dose of 100 mg/kg diet to experimental rats under hypercholesterolemic conditions evoked severe biochemical and pathological changes. Supplementation of chickpea (Cicer arietinum L.) seed coat fibre in the diet along with NDEA reduced its biochemical and pathological effects. There was a reduction in the hepatotoxic effects of NDEA as evidenced by decreased hepatic degeneration and improved liver weight index. Administration of NDEA resulted in a significant increase in the osmotic fragility of erythrocytes. The antioxidant activity of experimental animals decreased in the NDEA-fed group, which was evident by increased in vitro lipid peroxidation (LPO) of erythrocytes. However, chickpea seed coat fibre considerably reduced the peroxidative damage done by NDEA. Administration of NDEA also resulted in a significant increase in LPO in all the tissues to a varying degree, although the effect on antioxidant potential was variable in different tissues. However, chickpea seed coat fibre reduced the effect of NDEA on LPO and antioxidant potential of various tissues, providing reasonable protection against NDEA-induced oxidative stress and hence its toxicity. Histopathological analysis of different tissues (heart, liver and lungs) showed decrease in the severity of pathological changes among the experimental animals when they were given NDEA along with chickpea seed coat fibre in the diet as compared with giving NDEA alone. Our study therefore, emphasizes the importance of including dietary fibre in the diet, in combating the ill-effects of nitrosamines such as NDEA, particularly on the antioxidant status of the body.

Introduction

N-nitrosamines including N-nitrosodiethylamine (NDEA) are one of the important groups of carcinogens frequently present in human environment and food chain that pose a significant human health hazard (Aiub et al., 2003). Presence of these nitroso compounds, including NDEA, has been widely reported in various foodstuffs such as milk products, meat products, soft drinks and alcoholic beverages (Tricker et al., 1991; Prasad and Krishnaswamy, 1994; van Maanen et al., 1998; Levallois et al., 2000). Although the occurrence and concentration of these nitrosamines in common dietary items have been reduced considerably in the Western countries due to changes in the manufacturing procedures, processing and/or ingredients, their dietary levels in developing countries is still substantially high (Hotchkiss, 1989). In addition to this, tobacco usage in the developed as well as in the developing world is also one of the biggest causes for individual exposure to nitrosamines (Wu et al., 2005). Presence of these nitroso compounds in the diet together with the possibility of their endogenous formation in the human body by reaction of nitrite with amines and amides (Masuda et al., 2000; Ohsawa et al., 2003) has been of great concern since they are suggested to cause oxidative stress and cellular injury due to the involvement of reactive oxygen species (Bartsch et al., 1989; Bansal et al., 2005). In vitro studies from our lab in rat and human erythrocytes have shown that NDEA exposure increases lipid peroxidation (LPO) and decreases the activity of antioxidant enzymes (Bansal et al., 1996; Bansal and Bhatnagar, 1998). It is a well-known fact that oxygen-free radicals and related lipid peroxides also play a key role in the pathogenesis of normal senescence and of age-related chronic degenerative diseases, including atherosclerosis (Stocker and Keaney Jr, 2004; Maxwell and Lip, 1997). Hypercholesterolemia is known to be one of the major risk factors of atherosclerosis, which plays an important role in the pathogenesis of coronary artery disease, a major cause of premature deaths in the world (Maxwell, 2000).

The preventive and therapeutic benefits of dietary fibre including chickpea seed coat fibre against hypercholesterolemia are well known as a variety of epidemiological, animal and human studies have shown over the years (Gardner et al., 2005; Pittaway et al., 2004; Jenkins et al., 2003; Chu and Hanson, 2000). Dietary fibre, a component of food that resists the action of digestive enzymes in the gastrointestinal tract, reduces the rate of diffusion of the products of digestion towards absorptive surfaces (Bennett and Cerda, 1996). Scavenger action of fibre may lead to removal or slowing down of absorption of nitroso compounds such as NDEA, which in turn may reduce the risk of their toxic effects. We have already shown in our previous work, the toxicity of NDEA under hypercholesterolemic dietary conditions (Mittal et al., 2006). We now report the protective effect of chickpea seed coat fibre against this NDEA-induced toxicity and oxidative stress in hypercholesterolemic experimental rats.

Section snippets

Materials and methods

All the chemicals used in the present study were of analytical grade. NDEA was purchased from Sigma Chemical Company, St. Louis, MO, USA. Chickpea (Cicer arietinum L.) seed coat was procured from the local market. Fibre was prepared by the method as described by Mann et al. (2001).

Animal experiments were approved by the Social Justice and Empowerment Committee for the purpose of control and supervision of experiments on animals, Ministry of Government of India, New Delhi. Disease-free male

Results

Oral administration of NDEA to experimental rats under hypercholesterolemic conditions resulted in substantial decrease in feed intake, which improved with addition of chickpea seed coat fibre in the diet. A decrease in body weight was observed, which can be attributed to the decreased food intake (Table 1). NDEA administration also resulted in a significant hepatic degeneration as evident by a significant decrease in liver weight index (Table 1). However, the degenerative effects of NDEA were

Discussion

Although nitrosamines are known carcinogenic agents, their mechanism of action is not very well understood. Nitrosamines such as NDEA have been suggested to cause oxidative stress and cellular injury due to involvement of free radicals (Bansal et al., 2005; Bartsch et al., 1989). The free radicals initiate LPO, causing oxidative deterioration of the membrane lipids and other biomolecules (Gebicki et al., 2000; Spickett et al., 2000; Horton and Fairhust, 1987). NDEA has been shown to be

Acknowledgements

The authors are grateful to the Head, Department of Biochemistry and Chemistry for providing necessary facilities for the study, and to Mr. Avtar Singh for technical help.

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