Elsevier

Toxicology

Volume 189, Issue 3, 1 August 2003, Pages 223-234
Toxicology

Changes in some hematological and biochemical indices of rabbits induced by isoflavones and cypermethrin

https://doi.org/10.1016/S0300-483X(03)00145-8Get rights and content

Abstract

Protective effect of isoflavones on cypermethrin-induced changes in blood hematology, and plasma lipids, lipoproteins, glucose, urea, creatinine, total bilirubin and protein concentrations of male New Zealand White rabbits was studied. Rabbits were orally given sublethal dose of cypermethrin (24 mg/kg BW; 1/100 LD50), while isoflavones (2 mg/kg BW) was given alone or in combination with cypermethrin. The tested doses were given to rabbits every other day for 12 weeks. Results showed that cypermethrin caused a significant (P<0.05) increase in the levels of plasma total lipids (TL), cholesterol, triglyceride (TG), low density lipoprotein (LDL) and very low density lipoprotein (VLDL), while the level of high density lipoprotein (HDL) decreased. Isoflavones alone significantly (P<0.05) decreased the levels of TL, cholesterol, TG, LDL and VLDL, and increased HDL, and alleviated the harmful effects of cypermethrin on lipid profiles. Cypermethrin caused a significant (P<0.05) increase in glucose, urea, creatinine and total bilirubin. The concentrations of plasma total protein (TP) and albumin (A) were significantly (P<0.05) decreased in plasma of rabbits treated with cypermethrin, while globulin concentration and A/G ratio were not affected. Results showed that cypermethrin significantly (P<0.05) decreased hemoglobin (Hb), total erythrocytic count (TEC) and packed cell volume (PCV), while total leukocyte count (TLC) increased. Isoflavones alone did not cause any significant change in these parameters, but minimized the toxic effect of cypermethrin. Results demonstrated the beneficial influences of isoflavones in reducing the negative effects of cypermethrin on blood hematology and biochemical parameters of male rabbits.

Introduction

Pesticides are used widely in agriculture for control of insects all over the world with more than 10,000 commercial formulation of approximately 450 pesticidal compound currently in use (Cengiz et al., 2001). Pyrethroid insecticides were used preferably over organochlorines, organophosphates and carbamates due to their high effectiveness against a wide range of insects, low toxicity to non-target organisms (mammals) and easy biodegradibility. In spite of claims of low mammalian toxicity of synthetic pyrethroids, evidence is gradually accumulated against it (Shakoori et al., 1988). The presence of cypermethrin in environmental and occupational settings represents a true risk for exposed human beings. Cypermethrin is a widely used pyrethroid pesticide in the agricultural and hygienic application as well as in the household. Population at highest risk of high dose exposure are producers, hygienic and pesticide workers, and small farm owners applying cypermethrin for plant protection; low dose exposure originates mainly from the household application of insecticides (WHO-IPCS, 1989). During pyrethroid metabolism, reactive oxygen species (ROS) were generated and caused oxidative stress in intoxicated animals (Kale et al., 1999). Also, Ramasarma (2000) reported that free radicals produce oxidative deterioration of lipids, proteins and DNA. In vertebrates and invertebrates, cypermethrin acts mainly on the nervous system. Cypermethrin is both a stomach poison and a contact insecticide (Jin and Webster, 1998). Cypermethrin has been shown to inhibit ATPase enzymes involved in movement of ions against a concentration gradient, which are regulated by active transport (Siegfried, 1993).

During the past few years, estimation of free radical generation and antioxidant defense has become an important aspect of investigation in mammals (Zini et al., 1993). Recent studies were carried out to evaluate the potential role of antioxidant vitamins, such as, vitamin C, vitamin E, and β-carotene (Bagchi et al., 2000, Yousef et al., 1999a), and antioxidant minerals, such as, zinc and selenium (Pregiosi et al., 1998) for the protection of cells against oxidative damage due to pesticides toxicity. Soy beans and most soy products contain large amounts of the isoflavones genistein and daidzein (Franke et al., 1995). Isoflavones are currently receiving much attention because of their antioxidant activities (Widyarini et al., 2000). Genistein and diadzein, the most significant isoflavones, are heterocyclic phenols that have a structure similar to estrogen (Kaldas and Hugh, 1989). Naturally occurring phenolics have shown antioxidant activity in different model systems. These phenolics include soybean isoflavone glycosides (genistein, daidzein, glycitein) (Yurttas et al., 2000). Isoflavones are protective antioxidants, which they reduce the formation of radicals and reactive oxygen by decomposition of hydrogen peroxide without generating radicals, by quenching active singlet oxygen, and by trapping radicals before they reach a cellular target (Fran et al., 2000). Sierens et al. (2001) reported that antioxidant species (isoflavones) may act in vivo to decrease oxidative damage to DNA, protein and lipids thus reducing the risk of coronary disease and cancer. Possible mechanisms of isoflavones that have been studied in animals and humans include enhancement of bile acid excretion, reduced cholesterol metabolism, increased thyroid hormones, and reduced insulin to glucagon ratios (Potter, 1998). The hypocholesterolemic mechanisms of soy foods are still under investigation and the constituents of soy responsible for these serum lipid effects are under discussion (Sirtori et al., 1997). Therefore, the objectives of this study were to determine (1) the effects of sublethal dose of cypermethrin on blood hematology, lipids, lipoproteins, protein, glucose, urea, creatinine and total bilirubin concentrations of male rabbits, (2) the role of isoflavones in alleviating the negative effects of cypermethrin, and (3) the effect of isoflavones alone on hemato-biochemical parameters.

Section snippets

Materials and methods

Cypermethrin 25% E.C [(RS)-cyano-(3-phenoxyphenyl) methyl-(IRS)-cis-trans-3-(2,2-dichloroethenyl)-2,2-dimethyl-cyclopropane carboxylate] was purchased from Mitchell Cotts Chemicals, West Yorkshire, UK. Isoflavones (genistein/daidzein from soy concentrate) were supplied from California Health Products, Inc. 11577W. Olympic Bivd. Los Angeles, and CA90064. The dose of isoflavones was 2 mg/kg BW every other day. This dose was equivalent to double therapeutic dose for menopausal women (60 mg total

Results and discussion

Table 1 showed the over all means of plasma total lipid (TL), cholesterol, TG, HDL, LDL and VLDL concentrations, and Fig. 1, Fig. 2 represent these parameters expressed as % of control. The data indicated that plasma TL, cholesterol, TG, LDL and VLDL were significantly (P<0.05) increased by cypermethrin treatment, while HDL levels were decreased, and these results agree with the previous studies on sheep (Al-Qarawi et al., 1999), goats (Bose et al., 1996) and workers (Kossmann et al., 1993).

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