Ultrastructure, histology, and histochemistry of an acute myopathy in guinea pigs given ...

129 Pages·2016·2.64 MB·English

by  W. Michael Peden

Iowa State University Capstones, Theses and
Retrospective Theses and Dissertations
Dissertations
1989
Ultrastructure, histology, and histochemistry of an
acute myopathy in guinea pigs given cyclopiazonic
acid
W. Michael Peden
Iowa State University
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Recommended Citation
Peden, W. Michael, "Ultrastructure, histology, and histochemistry of an acute myopathy in guinea pigs given cyclopiazonic acid "
(1989).Retrospective Theses and Dissertations. 9075.
https://lib.dr.iastate.edu/rtd/9075
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Order Number 9003555
Ultrastructure, histology, and histochemistry of an acute
myopathy in guinea pigs given cyclopiazonic acid
Peden, W. Michael, Ph.D.
Iowa State University, 1989
U M I
300N.ZeebRd.
Ann Arbor, MI 48106

I
Ultrastructure, histology, and histochemistry
of an acute myopathy in guinea pigs
given cyclopiazonic acid
by
W. Michael Peden
A Dissertation Submitted to the
Graduate Faculty in Partial Fulfillment of the
Requirements for the Degree of
DOCTOR OF PHILOSOPHY
Major: Veterinary Pathology
Approved:
Signature was redacted for privacy.
In^harge of Major Work
Signature was redacted for privacy.
the Major Department
Signature was redacted for privacy.
For the Graduate College
Iowa State University
Ames, Iowa
1989
ii
TABLE OF CONTENTS
GENERAL INTRODUCTION 1
LITERATURE REVIEW 3
MUSCLE 10
ULTRASTRUCTURE, HISTOLOGY, AND HISTOCHEMISTRY
OF AN ACUTE MYOPATHY IN GUINEA PIGS GIVEN
CYCLOPIAZONIC ACID 15
ABSTRACT 17
INTRODUCTION 18
MATERIALS AND METHODS 20
RESULTS 23
DISCUSSION 46
REFERENCES 53
CYCLOPIAZONIC ACID EFFECTS ON GUINEA PIG
SKELETAL MUSCLE AND LIVER VITAMIN E 63
ABSTRACT 65
INTRODUCTION 66
METHODS AND MATERIALS 68
RESULTS 70
DISCUSSION 102
REFERENCES 106
SUMMARY 111
BIBLIOGRAPHY 113
ACKNOWLEDGEMENTS 121
1
GENERAL INTRODUCTION
The modem era of mycotoxlcology began with studies on the outbreak
of Turkey "X" Disease in England in 1961^'®^. The agents responsible for
the death loss, decreased productivity, toxic hepatitis and biliary
hyperplasia were ultimately determined to be mycotoxins. These
mycotoxins were named aflatoxins, after the organism that producedt hem,
Aspergillus flavus^'^'^^. .
The original feedstuff implicated in Turkey X disease( Brazilian
peanut meal) contained mycelial fragments, but no fungus was isolated
from the peanut meal. Early experimental work was done with a fungal
isolate obtained from a similar outbreak involving Ugandan peanut
meal^'^G This isolate was originally believed to be an isolate of
A.flavus. but was later determined to be an isolate of Aspergillus
Û
parasiticus^.
The variation in clinical signs noted in Turkey X disease versus
experimental aflatoxicosis led Cole (1986) to suggest that another
mycotoxin, cyclopiazonic acid, might have been involved in the original
outbreak^.
Cyclopiazonic acid (CPA) was originally isolated from Pénicillium
cvclopium Westling27 during routine screening of cultures of Pénicillium
spp. It was suggested as a secondary mycotoxin in Turkey X disease
because several studies had demonstrated that various Aspergillus sp.
could produce both aflatoxin and CPA^®'^^, but A^. parasiticus isolates
had not been shown to produce CPA^^. Additionally, administration of CPA
2
caused clinical signs similar to the original descriptions of Turkey X
disease®»^.
In studies to test the synergism of aflatoxin and CPA, guinea pigs
intoxicated with CPA demonstrated dyskinesia when forced to exercisers.
Microscopic examination of skeletal musclé from guinea pigs in
preliminary dose-related studies^l (unpublished) demonstrated myofiber
degeneration and necrosis. The objectives of the following experiments
were to determine the pathogenesis of the muscle lesion, to characterize
the lesion, and to determine which fiber types were involved.
3
LITERATURE REVIEW
Cyclopiazonic acid (CPA) is a mycotoxin originally isolated from
Pénicillium cvcloptum Uestling by Holzapfel^? in 1968. CPA has been
characterized as a toxic indole tetramlc acid, similar to the mycotoxlns
tenuazonic acid and erythroskyrine, and acts as a lipophilic monobasic
acid 27,28,29,30,60
Cyclopiazonic acid has been isolated as a naturally occurring
mycotoxin from corn, peanuts, cheese, and millet20'34,36,59 Several
fungi in the Pénicillium and Aspergillus genera have been shown to
produce CPA, among them Pénicillium cvclopium. P. patulum. P.
virldicatum. P. puberlum. P. crustosum. P. camembert!. Aspergillus
versicolor. A. orvzae. A. tamarii. and ^ flavus
13,14,15,35,36,37,39,49,50,61 cp^ may be a more common metabolite of
A^ flavus than aflatoxin, as one study has shown that 19 of 31 isolates
of ^ flavus detected in dried food products produced CPA, while only 6
of the 31 isolates produced aflatoxin®^.
Cyclopiazonic acid has been implicated as a possible factor in
"kodua "54. Kodua poisoning is associated with ingestion of
poisoning
moldy millet (Paspalum scrobiculatum)Clinical signs in livestock
include depression, nervousness, incoordination and spasms^^. In man,
ingestion of infected grain results in clinical signs of tremors and
sleepiness. An extract from the infected grain produced depression and
loss of mobility when injected into mice, and CPA was identified in the
extract. Two fungi, Aspergillus flavus and A^ tamarii were consistently