Mycotoxins

Mycotoxins are secondary fungal metabolites. They induce toxic effects upon inhalation or consumption by humans or animals. Mass-poisonings by mycotoxins are unusual in humans.

The history of human intoxications by mycotoxins (mycotoxicoses) dates back to the Middle Ages, when epidemics of hallucinations, delirium, convulsions, and gangrene were not uncommon. By the 1850s, the ergot alkaloids (products of the fungus Claviceps purpurea) were identified as the causative agents of the disease. Renewed interest in mycotoxin-caused diseases resulted from the death of thousands of turkeys and ducks (Turkey X disease) in England in the early 1960s. The animals were fed diets containing peanut meal contaminated by so-called aflatoxins, products of the fungus Aspergillus flavus. In the last three decades, more than 100 mycotoxins have been identified throughout the world. Two more classes of mycotoxins posing health hazards are the ochratoxins and trichothecenes.

11.3.1.1 Ergot alkaloids Recurrent poisonings by ergot alkaloids (ergotism) in the past resulted from the consumption of Claviceps purpurea-infected rye as bread. All ergot alkaloids are derivatives of lysergic acid, with ergonovine (ergometrine) and ergotamine as the most important ones.

O HOC

O HOC

CH3 Lysergic acid

CH3 Lysergic acid

Ergotamine

HOCH2CHNHC

Ergonovine

HOCH2CHNHC

Ergonovine

Ergotamine

H CH2C6H5

H CH2C6H5

Ergotism can manifest itself in two ways: a gangrenous type and a convulsive type. The first syndrome is characterized by intense tingling of and hot and cold sensations in the limbs, followed by progression to gangrene and mummification of the extremities. Gangrenous ergotism is largely due to long and intense peripheral vasoconstriction. Ergot alkaloids are partial a-adrenergic agonists. They promote vasoconstriction.

The convulsive syndrome includes central nervous system symptoms such as vomiting, headache, numbness, muscle spasm, and convulsions. Ergonovine has been reported to increase uterine motility, which may cause abortion.

Epidemic ergotism has almost been eliminated. In 1977 and 1978, cases were reported in Ethiopia. In rye, low levels of contamination with ergot alkaloids may still occur.

11.3.1.2 Aflatoxins

Aflatoxins are highly substituted coumarin derivatives that contain a fused dihydrofuran moiety. They are divided into two major groups: the B-group (with a cyclopentanone ring) and the G-group (with a lactone ring), based on blue and green fluorescence (Figure 11.5).

Foodstuffs most likely to become contaminated by aflatoxins are peanuts, various other nuts, cottonseed, corn, and figs. Human exposure can also occur from intake of aflatoxins from tissues and milk (in particular aflatoxin M1, a metabolite of aflatoxin B1) from animals that have eaten contaminated feeds.

The group of aflatoxins includes hepatotoxicants and carcinogens. Hepatotoxicity seen in experimental animals is characterized by bile duct epithelium proliferation, fatty infiltration, and centrilobular necrosis. Aflatoxin B1 is highly hepatotoxic and one of the most potent hepatocarcinogens in rats. In many cell systems, it has also been demonstrated to be a mutagen. The hepatotoxicity as well as the mutagenicity and carcinogenicity are believed to depend on its activation by cytochrome P-450 to the 2,3-epoxide. This potent electrophile can covalently bind to proteins and form adducts with DNA.

Epidemiological data indicate that there is a difference in risk of liver cancer between populations in Asia and Africa on the one hand and in North America on the other. Recent studies on the occurrence of hepatitis B virus suggest that chronic infection may contribute to a higher incidence of liver cancer in aflatoxin-exposed populations. In experimental animals, aflatoxin B1 has been shown to suppress cell-mediated immunity.

11.3.1.3 Ochratoxins

Ochratoxins are a group of seven dihydroisocoumarin derivatives. The isocoumarin moiety is linked to phenylalanine by an amide bond. Further, some of the ochratoxins distinguish themselves from other mycotoxins by possessing a chlorine atom (Figure 11.6). Ochratoxins have been identified in grains, soybeans, peanuts, and cheese.

Epidemiological studies on the cause of nephropathy in several areas of Yugoslavia, Rumania, and Bulgaria in the late 1950s presented evidence implicating ochratoxin A, present in foodstuffs infected by Aspergillus ochraceus and a number of other Aspergillus and Penicillium species. A similar nephropathy was observed in swine in Denmark and the US. Symptoms include necrosis, fibrosis, and decreased glomerular filtration. In cattle, the ochratoxins undergo degradation by ruminal microorganisms. In addition to nephropa-thy, ochratoxins have been reported to induce teratogenic effects, renal adenomas, and hepatomas in mice. Tests for mutagenicity, however, gave negative results.

11.3.1.4 Trichothecenes

The trichothecene mycotoxins constitute a group of more than 80 sesquiterpenes, derivatives of 12,13-epoxytrichothecene. In the first half of this century, outbreaks of a mycotoxi-cosis associated with the consumption of contaminated food were reported in Russia. The disease, called alimentary toxic aleukia (ATA), caused atrophy of bone marrow, agranu-locytosis, necrotic angina, sepsis, and death. Later, it was related to the infection of grains

O r4

Aflatoxin B1 and its derivatives

Aflatoxin B1 and its derivatives

Aflatoxin R1 R2 R3 R4 R5 R6

B1

H

H

H

= O

H

OCH,

B2

H2

H2

H

= O

H

OCH,

B2a

HOH

H2

H

= O

H

OCH,

M1

H

H

OH

= O

H

OCH,

M2

H2

H2

OH

= O

H

OCH,

P1

H

H

H

= O

H

OH

Q1

H

H

H

= O

OH

OCH,

R0

H

H

H

OH

H

OCH,

Aflatoxin G1 and its derivatives
Aflatoxin R1 R2 R3

G1

H

H

H

G2

H2

H2

H

G2a

OH

H2

H

GM1

H

H

OH

Figure 11.5 Structures of aflatoxins.

with Fusarium species. The most important source of trichothecenes is the fungus genus Fusarium. The main contaminants of grains are T-2 toxin and 4-deoxynivalenol (vomitoxin).

(CH3)2HCH2CCOO

T-2 toxin

Deoxynivalenol

CH2 OH I CH3

Deoxynivalenol

There are two forms of trichothecene-caused toxicosis: an acute form, characterized by neurological signs, and a chronic form, characterized by signs of dermanecrosis, leukope-©1997 CRC Press LLC

Ochratoxin

Ochratoxin

methylester A methyl or ethylester B

C2H5

CH3 or C2H5

Figure 11.6 Structures of ochratoxins.

nia, and gastrointestinal inflammation, and hemorrhages.

Many toxic effects of trichothecenes are believed to originate from inhibition of protein synthesis. Trichothecenes are generally recognized as the most potent inhibitors of protein synthesis in eukaryotic cells. The inhibition can take place at the initiation, elongation as well as termination phases.

In animals, the trichothecenes are rapidly metabolized to nontoxic compounds. They undergo deacetylation, hydroxylation, and glucuronidation in the liver and kidneys. This detoxication mechanism may contribute to the reduction of the risks in humans from dietary intake of trichothecenes.

Was this article helpful?

0 0
10 Ways To Fight Off Cancer

10 Ways To Fight Off Cancer

Learning About 10 Ways Fight Off Cancer Can Have Amazing Benefits For Your Life The Best Tips On How To Keep This Killer At Bay Discovering that you or a loved one has cancer can be utterly terrifying. All the same, once you comprehend the causes of cancer and learn how to reverse those causes, you or your loved one may have more than a fighting chance of beating out cancer.

Get My Free Ebook


Post a comment