血液生化参数
相关主题
- 1、下载文档前请自行甄别文档内容的完整性，平台不提供额外的编辑、内容补充、找答案等附加服务。
- 2、"仅部分预览"的文档,不可在线预览部分如存在完整性等问题,可反馈申请退款(可完整预览的文档不适用该条件!)。
- 3、如文档侵犯您的权益，请联系客服反馈,我们会尽快为您处理(人工客服工作时间：9:00-18:30)。
*To whom correspondence should be addressed at: Laborataire de Toxicologic et d’Hygiene Faculte de Pharmacie, Universite de Bordeaux 2, 146 Rue Leo Saignat, 33076 Bordeaux, France. 535 Appliquee,
MATERIALS AND METHODS
Zearalenone(Sigma Chemical.
(5 mg/ml) for the stock injection into animals.
Animals and treatments
solution
St Louis, MO, U.S.A.) was dissolved in pure sterile olive oil which was diluted in the same oil when necessary, before
K. Maaroufi, L. Chekir, E. E. Creppy, F. Ellouz and H. Bacha. Zearalenone induces modifications of haematological and biochemical parameters in rats. Toxicon 34, 5355540, 1996.-Zearalenone produced by the fungus Fusarium roseum causesimportant perturbations in the gestation cycle of the rat with hormonal disorders and infertility. In order to find out other eventual toxic effects, female rats were given intraperitoneally (i.p.) (1.5, 3 and 5 mg/kg) zearalenone in sterile olive oil. Forty-eight hours later, some blood parameters changed (hematocrit, MCV, the number of platelets and WBC) as well as some biochemical markers such as aminotransferases (ALT, AST), alkaline phosphatase (ALP), serum creatinine, bilirubin, indicating liver toxicity, and likely impairment of blood coagulation process.Copyright 80 1996 Elsevier Science
ZEARALENONE INDUCES MODIFICATIONS HAEMATOLOGICAL AND BIOCHEMICAL PARAMETERS IN RATS
KHIRA MAAROUFI.’ FARIELLE LEILA CHEKIR,’ EDMOND EKUE ELLOUZ’ and HASSEN BACHA’
Ltd.
INTRODUCTION
Zearalenone (Zen) (F2-Toxin) is a naturally occurring oestrogenic substanceproduced by speciesof Fusarium fungi growing on grains, mainly corn and hay exposed to high moisture on storage (Mirocha et al., 1968; Mirocha and Christensen, 1974). Its toxicokinetics shows distribution in reproductive organs and mainly in uterus and ovaries (Fitzpatrick et al., 1989). A health risk to man has been reported, for example precocious pubertal change in children in Puerto-Rico and high incidence of oesophagealcancer in Africa and in China due to zearalenone ingestion (Saenz de Rodriguez et al., 1985; for a review see Kuiper-Goodman et al., 1987). Rats are approximately 10 times more sensitive than mice (Bacha et al., 1993) with a NOAEL (no-observed adverse effect level) greater than 1.5 mg/kg for osteopetrosis (National Toxicology Program U.S.A., 1982; for a review, see Kuiper-Goodman et al., 1987). In swine, which is the most sensitive domestic animal, a concentration as low as 5 ppm in the feed induced pseudopregnancy with a failure to cycle (Farnworth and Trenholm,
Pergamon SOO41-0101Leabharlann Baidu96)00008-6
Copynght
t
l-mcon. Vol. 34. No. 5. pp. 535-540. 1996 1996 Elsewer Saence Ltd. Ail rights reserved Printed in Great Britain 0041~0101;96 $15.00 + 0.00
2.4-deoxy-zearalenone
1983; Bauer et al., 1987; Etienne and Jemmali, 1982; William et al., 1989). The risk assessment of zearalenone has been recently reviewed by Kuiper-Goodman et al. (1987). The metabolism of zearalenone seems to occur essentially in the liver leading to alpha and beta zearalenol, the latter being not toxic (Fitzpatrick et al., 1989) whereas alpha zearalenol binds 10-20 times more than the parent compound and 100 times more than beta zearalenol to oestrogen receptors (Fitzpatrick et al., 1989). This could be related to its structure (Fig. 1) which shows similarities with oestrogenic steroids. It has been shown that zearalenone possibly combined to its derivatives impairs the oestrogenic-controlled gene expression in cultured cells (Mayr, 1988) and more recently decreases in vivo the serum progesterone levels (Bacha et al., 1993). Data from the National Toxicology Program (U.S.A.) (1982) showed that zearalenone induced hepatocellular adenomas together with pituitary glands tumours, indicating that these tissues could be the two main target ongans for zearalenone in vivo. In order to get a general view on the toxicology of zearalenone, mainly liver and kidney toxicity, other possible adverse effects on blood enzymes or biological markers have been investigated after intraperitoneal (i.p.) injection of zearalenone into female rats.
536
K. MAAROUFI
et al
Fig. RI OH OH H R2 OH OH H
1. Chemical R1 0 OH 0
structure Rq H H OH
of zearalenone CI and C? -CH=CH--CH=CH--CH&H-
and some derivatives. Name Zearalenone Zearalenol 5-Hydroxy
Female Wistar rats 200 g + 10 were randomised in 5 groups of 10 animals. Group C,: control animals with no treatment at all. Group C: control animals injected with olive oil only. Group 1.5: animals treated with zearalenone (1.5 mg/kg). Group 3: animals treated with zearalenone (3 mg/kg). Group 5: animals treated with zearalenone (5 mglkg). Animals were kept until they get used to the conditions of housing, feeds, temperature, humidity, light and dark cycle and stress if any, for approximately one week. Animals were injected i.p. a total volume of 200 ~1 of oil or zearalenone oil-solution.
OF
CREPPY,‘*
‘Laboratoire de Biochimie et de Toxicologic Moleculaire, Fact&e de Medecine Dentaire, rue Avicennes SO19 Monastir, Tunisie and ‘Laboratoire de Toxicologic et d’Hygi&ne Appliquee, Faculte de Pharmacie, Universitt de Bordeaux 2. 146 Rue Leo Saignat, 33076 Bordeaux France. (Received 23 October 1995; accepted 3 Januur~ 1996)
MATERIALS AND METHODS
Zearalenone(Sigma Chemical.
(5 mg/ml) for the stock injection into animals.
Animals and treatments
solution
St Louis, MO, U.S.A.) was dissolved in pure sterile olive oil which was diluted in the same oil when necessary, before
K. Maaroufi, L. Chekir, E. E. Creppy, F. Ellouz and H. Bacha. Zearalenone induces modifications of haematological and biochemical parameters in rats. Toxicon 34, 5355540, 1996.-Zearalenone produced by the fungus Fusarium roseum causesimportant perturbations in the gestation cycle of the rat with hormonal disorders and infertility. In order to find out other eventual toxic effects, female rats were given intraperitoneally (i.p.) (1.5, 3 and 5 mg/kg) zearalenone in sterile olive oil. Forty-eight hours later, some blood parameters changed (hematocrit, MCV, the number of platelets and WBC) as well as some biochemical markers such as aminotransferases (ALT, AST), alkaline phosphatase (ALP), serum creatinine, bilirubin, indicating liver toxicity, and likely impairment of blood coagulation process.Copyright 80 1996 Elsevier Science
ZEARALENONE INDUCES MODIFICATIONS HAEMATOLOGICAL AND BIOCHEMICAL PARAMETERS IN RATS
KHIRA MAAROUFI.’ FARIELLE LEILA CHEKIR,’ EDMOND EKUE ELLOUZ’ and HASSEN BACHA’
Ltd.
INTRODUCTION
Zearalenone (Zen) (F2-Toxin) is a naturally occurring oestrogenic substanceproduced by speciesof Fusarium fungi growing on grains, mainly corn and hay exposed to high moisture on storage (Mirocha et al., 1968; Mirocha and Christensen, 1974). Its toxicokinetics shows distribution in reproductive organs and mainly in uterus and ovaries (Fitzpatrick et al., 1989). A health risk to man has been reported, for example precocious pubertal change in children in Puerto-Rico and high incidence of oesophagealcancer in Africa and in China due to zearalenone ingestion (Saenz de Rodriguez et al., 1985; for a review see Kuiper-Goodman et al., 1987). Rats are approximately 10 times more sensitive than mice (Bacha et al., 1993) with a NOAEL (no-observed adverse effect level) greater than 1.5 mg/kg for osteopetrosis (National Toxicology Program U.S.A., 1982; for a review, see Kuiper-Goodman et al., 1987). In swine, which is the most sensitive domestic animal, a concentration as low as 5 ppm in the feed induced pseudopregnancy with a failure to cycle (Farnworth and Trenholm,
Pergamon SOO41-0101Leabharlann Baidu96)00008-6
Copynght
t
l-mcon. Vol. 34. No. 5. pp. 535-540. 1996 1996 Elsewer Saence Ltd. Ail rights reserved Printed in Great Britain 0041~0101;96 $15.00 + 0.00
2.4-deoxy-zearalenone
1983; Bauer et al., 1987; Etienne and Jemmali, 1982; William et al., 1989). The risk assessment of zearalenone has been recently reviewed by Kuiper-Goodman et al. (1987). The metabolism of zearalenone seems to occur essentially in the liver leading to alpha and beta zearalenol, the latter being not toxic (Fitzpatrick et al., 1989) whereas alpha zearalenol binds 10-20 times more than the parent compound and 100 times more than beta zearalenol to oestrogen receptors (Fitzpatrick et al., 1989). This could be related to its structure (Fig. 1) which shows similarities with oestrogenic steroids. It has been shown that zearalenone possibly combined to its derivatives impairs the oestrogenic-controlled gene expression in cultured cells (Mayr, 1988) and more recently decreases in vivo the serum progesterone levels (Bacha et al., 1993). Data from the National Toxicology Program (U.S.A.) (1982) showed that zearalenone induced hepatocellular adenomas together with pituitary glands tumours, indicating that these tissues could be the two main target ongans for zearalenone in vivo. In order to get a general view on the toxicology of zearalenone, mainly liver and kidney toxicity, other possible adverse effects on blood enzymes or biological markers have been investigated after intraperitoneal (i.p.) injection of zearalenone into female rats.
536
K. MAAROUFI
et al
Fig. RI OH OH H R2 OH OH H
1. Chemical R1 0 OH 0
structure Rq H H OH
of zearalenone CI and C? -CH=CH--CH=CH--CH&H-
and some derivatives. Name Zearalenone Zearalenol 5-Hydroxy
Female Wistar rats 200 g + 10 were randomised in 5 groups of 10 animals. Group C,: control animals with no treatment at all. Group C: control animals injected with olive oil only. Group 1.5: animals treated with zearalenone (1.5 mg/kg). Group 3: animals treated with zearalenone (3 mg/kg). Group 5: animals treated with zearalenone (5 mglkg). Animals were kept until they get used to the conditions of housing, feeds, temperature, humidity, light and dark cycle and stress if any, for approximately one week. Animals were injected i.p. a total volume of 200 ~1 of oil or zearalenone oil-solution.
OF
CREPPY,‘*
‘Laboratoire de Biochimie et de Toxicologic Moleculaire, Fact&e de Medecine Dentaire, rue Avicennes SO19 Monastir, Tunisie and ‘Laboratoire de Toxicologic et d’Hygi&ne Appliquee, Faculte de Pharmacie, Universitt de Bordeaux 2. 146 Rue Leo Saignat, 33076 Bordeaux France. (Received 23 October 1995; accepted 3 Januur~ 1996)