Effects on antioxidant status of liver following atrazine exposure and its attenuation by vitamin E

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Abstract

In the present investigation, the effect of atrazine on antioxidant enzymes and body weight was studied in male Wistar rats. Atrazine (300 mg/kg bw) was administered by gavage for 7, 14 and 21 days. A significant increase in hepatic lipid peroxidation (LPO) was observed following atrazine administration. Vitamin E treatment (100 mg/kg bw), on the otherhand, attenuated atrazine-induced LPO in liver. In addition, vitamin E treatment restored the GSH content and glucose-6-phosophate dehydrogenase activity that was found to be lowered after atrazine administration. The activities of antioxidant enzymes: superoxide dismutase, catalase, glutathione peroxidase and glutathione-s-transferase were significantly increased following atrazine administration and vitamin E treatment could restore these activities. In conclusion, the results of the study demonstrate that atrazine induces oxidative stress in terms of enhanced lipid peroxidation. However, vitamin E treatment ameliorated the effects of atrazine suggesting it as potential antioxidant against atrazine-induced oxidative stress.

Introduction

Herbicides control or kill plants through a variety of mechanisms, including the inhibition of biological processes, such as photosynthesis, mitosis, cell division, enzyme function, root growth, or leaf formation, interference with the synthesis of pigments, protein or DNA, destruction of cell membranes; or the promotion of uncontrolled growth (William et al., 1995). Atrazine is a triazine herbicide that is used as a selective pre-emergence and post-emergence herbicide for the control of weeds in asparagus, maize, sorghum, sugarcane and pineapple. It is also used in forestry and for non-selective weed control on non-crop areas. It has been employed extensively in agriculture in the US and worldwide for over 40 years (Worthing 1991; US EPA, 1994). Atrazine is readily absorbed through the gastrointestinal tract. On administration of a single dose of atrazine (0.53 mg) to rats by gavage, 20% of it was excreted in feces within 72 h and 80% was absorbed across the gastrointestinal tract into the bloodstream (Hayes and Laws, 1990). Human exposure pathways for this chemical include occupational exposure through both inhalation and dermal absorption during its manufacture, its formulation and its application by spraying. Although, atrazine generally has low level of bioaccumulation in fish, it does accumulate in brain, gall bladder, liver and gut of some fishes (Eisler, 1989). Therefore, consumption of contaminated fish can also contribute to human exposure. Earlier studies from our laboratory have suggested that atrazine induces genotoxicity in liver and alters erythrocyte membrane structure in rats (Singh et al., 2008a, Singh et al., 2008b).

Previously, Gojmerac et al. (1995) had reported hepatic degeneration in pigs following atrazine exposure. Pesticides and herbicides induce hepatotoxicity, as liver is major site for detoxification of these compounds. The detoxification reactions of atrazine can be divided into phase I and phase II reactions. The major phase I metabolic reaction in plants and mammals is cytochrome P450-mediated N-dealkylation, while the phase II reaction is the glutathione-s-transferases (GST) catalyzed conjugation with glutathione (GSH) (Elia et al., 2002). Herbicides such as paraquat are known to exert their effects by inducing oxidative stress in tissues of mammals and fish (Winston and Di Giulio,1991). To prevent oxidation-induced damage, there are effective antioxidant systems in organisms. Some components of these systems are GSH and certain antioxidant enzymes including free radical scavenging enzymes, such as glutathione peroxidase (GPx), superoxide dismutase (SOD) and catalase. Other associated antioxidant enzymes are glutathione reductase (GR) and GST.

Non-enzymatic antioxidants such as α-tocopherol (vitamin E), ascorbate (vitamin C), β-carotene (vitamin A), flavonoids (quercetin, rutin, etc.), selenium and thiol containing compounds such as glutathione (GSH) can also act to overcome the oxidative stress, being a part of total antioxidant system (Sies et al., 1992). Vitamin E is an important biological free radical scavenger in the cell membranes (Horwitt, 1976). In the present investigation we studied whether vitamin E has the potential to attenuate atrazine-induced oxidative stress.

Section snippets

Chemicals

Atrazine (technical grade 97.83%) was a gift from Meghmani Industries Ltd. (India). Vitamin E (α-tocopheryl acetate, trade name – Evion) was obtained from Merck Pharmaceuticals, India. All other chemicals used were of analytical grade procured from local commercial sources.

Animals

Male rats (wistar strain), weighing about 100–120 g, were used throughout the studies. The animals were procured from the Central Animal House of the Panjab University. The animals were housed in polypropylene cages, provided

Body weight and liver weight

The changes in the body weight of the animals of various groups are shown in Table 1. A progressive increase in the body weight of rats was observed in the control and vitamin E treated groups. Maximum gain in the body weight was observed in the vitamin E treated rats as compared to all other groups. The administration of atrazine resulted in the loss of body weight of the rats. The reduction in body weight was pronounced in animals treated with atrazine for 21 days. After exposure with

Discussion

The decrease in the body weight following atrazine administration is in accordance with reports in literature of decrease in body weight following exposure to pesticides (Kennedy, 1986; Sharma et al., 2005). Roloff et al. (1992) observed decrease in body weight after the atrazine administration in mice. The decrease in the body weight after atrazine administration could be due to reduced diet intake or due to necrotic changes in the various body tissues (Gojmerac et al.,1995). The gain in body

Conclusion

From the above observations it can be concluded that exposure of atrazine results in increased oxidative stress and altered antioxidant status of the liver. Administration of vitamin E along with atrazine resulted in partial normalization of the toxic effects of atrazine thus highlighting the protective action of vitamin E.

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