The effect of zearalenone on some enzymatic parameters in rabbits

doi:10.1016/S0378-4274(01)00312-5

Toxicology Letters

Volume 121, Issue 3, 19 May 2001, Pages 145-149

https://doi.org/10.1016/S0378-4274(01)00312-5 Get rights and content

Abstract

The effects of low (10 μg/kg b.w.) and high (100 μg/kg b.w.) doses of mycotoxin-zearalenone on selected blood serum enzyme activities of aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), gamma-glutamyltransferase (GGT), and total lactatedehydrogenase (LD) of rabbits were studied. The toxin was administered orally for 14 days. In the experimental group E₁ (10 μg/kg b.w.), a significant increase in ALP activity was observed at 168 and 336 h during the experiment. In the 100 μg zearalenone sera (group E₂), significant increases in activities of AST, ALT, ALP, GGT, and LD were observed at 168 and 336 h, indicating possible liver toxicity due to chronic effects of the toxin.

Introduction

Zearalenone (F-2 toxin) is a toxin produced by fungi belonging to the genus Fusarium. These fungi contaminate corn, as well as food mixtures for farm animals (Bauer et al., 1980, Dutton and Kinsey, 1996, Molto et al., 1997). The toxin is the main metabolite of secondary metabolism of Fusarium (F.) roseum and F. graminearum (Gedek, 1980), but it was also found in F. culmorum (Jesenská, 1987). Zearalenone belongs to toxins with strong oestrogenic effects (Koch, 1981). There are also data on its capability to induce adverse liver lesions with subsequent development of hepatocarcinoma (National Toxicology Program USA, 1982).

Because fusaria occurred also in grain seeds in Slovakia (Jesenská et al., 1983, Šrobárová, 1997), and because of cereal food mixtures used in some species in animal production, the study of zearalenone's effects on animal health has become topical.

The aim of our work was to study zearalenone effects on the changes in enzymatic activities of aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), gamma-glutamyltransferase (GGT), and total lactatedehydrogenase (LD) in terms of the response of an organism to damage.

Section snippets

Material and methods

In the experiment, 20 female rabbits (Chinchilla Giganta, drobnochov Košice) were used (average body weight: 3.4±0.5 kg; age: 1 year old). The animals were divided into four groups, each of five animals, and placed into cages. The standard hygiene in the housing corresponded to the principles of The European Convention on Animal Protection (1986). The animals were given a commercial food mixture, KK (Kendice), and drinking water ad libitum. In the experimental group E₁, the 10 μg of zearalenone

Results

Table 1 presents activities of AST, ALT, ALP, LD, and GGT recorded at the sampling intervals. In the experimental group E_2, significantly higher activities of AST were observed at 168 h compared with both experimental groups C₁ (P<0.05) and C₂ (P<0.001), and at 336 h with the group C₂ (P<0.001). In this group, significant differences (P<0.001) were observed also between the AST activity at first sampling (0 h) and the activities at 168 and 336 h.

Activity of ALT was significantly higher in the

Discussion

Mycotoxins represent one of the negative factors influencing health of animals. The effects of aflatoxins and ochratoxins are quite well known. Recently, intense attention has been paid to toxins of fusaria including zearalenone. Even low doses (1 ppm) of this toxin lead to fertility disorders of swine and cattle (Schweighardt, 1980). Higher doses (50–100 ppm) affect conception, ovulation, implantation, foetal development, and viability of new-borns (Price et al., 1993).

Metabolism of

Acknowledgements

This work was partially supported by VEGA: Grant No. 1/7026/20

References (19)

K. Maaroufi et al.
Zearalenone induces modifications of haematological and biochemical parameters in rats
Toxicon
(1996)
M. Olsen et al.
Metabolism of high concentrations of dietary zearalenone by young male turkey poults
Poult. Sci.
(1986)
J. Bauer et al.
Zur Kontamination von Futtermitteln mit toxinbildenden Fusarienstämmen und deren Toxinen
Wien. tieräztl. Mschr.
(1980)
J. Blahovec et al.
M.F. Dutton et al.
A note on the occurrence of mycotoxins in cereals and animal feedstuffs in Kwazulu Natal, South Africa. South Africa 1984–1993
J. Anim. Sci.
(1996)
B. Gedek
J. Homolka
J. Horejši et al.

There are more references available in the full text version of this article.

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The effect of zearalenone on some enzymatic parameters in rabbits

Abstract

Introduction

Section snippets

Material and methods

Results

Discussion

Acknowledgements

Toxicon

Poult. Sci.

Zur Kontamination von Futtermitteln mit toxinbildenden Fusarienstämmen und deren Toxinen

Wien. tieräztl. Mschr.

A note on the occurrence of mycotoxins in cereals and animal feedstuffs in Kwazulu Natal, South Africa. South Africa 1984–1993

J. Anim. Sci.