THE HYPERLIPIDEMIC RESPONSE TO MYCOTOXINS

 

Cyclosporine-Induced Hyperlipdemia

 

Accelerated atherosclerosis is a leading cause of death in longterm survivors of heart and renal transplantation and is associated with the frequent occurrence of post transplant hyperlipidemia. Attempts to define the mechanism for hyperlipidemia in transplant recipients are confounded by dramatic changes in metabolism and nutritional status which occur after transplantation. The need to ascertain the effects of cyclosporine in non-transplantation was clear and led to appropriate studies. The results as shown below conclusively proved that cyclosporine is the sole cause of significant hyperlipidemia.

 

Cyclosporine-Induced Elevations of Cholesterol and Low Density Lipoproteins

Ballantyne et al (1989) studied the effects of cyclosporine therapy on plasma lipid levels in a humans and observed significant increases of 21% in total cholesterol, 31% in lowdensity lipoprotein cholesterol, and 12% in apolipoprotein B levels occurred only in the cyclosporine group and not in the controls. They concluded that cyclosporine therapy alone adversely affects plasma lipoprotein levels by increasing total cholesterol levels, primarily due to an increase in lowdensity lipoprotein cholesterol level.

Cyclosporine-Induced Hypertriglyceridemia and Hypercholesterolemia

 

Vathsala et al (1989) documented in a group of 500 cyclosporinetreated patients documented a 37.6% incidence of hypercholesterolemia, which occurred within 6 months posttransplant in 82% of patients. There was a synergistic effect seen when the corticosteroid therapy was added.

Hypertriglyceridemia, which was present in 14.7% of the patients, was also more severe under cyclosporineprednisone regimes.

 

Sporidesmin-Induced Hyperlipidemia

 

Sporidesmin is a highly toxic metabolic product of the fungus

 Pithomyces chartarum found in New Zealand vegetation upon which domestic animals, particularly sheep graze. The mycotoxin causes elevated serum levels of triglycerides and cholesterol associated with vascular lipid-containing lesions.

Interestingly, Peters (1966) observed that sporidesmin also induces biliary cirrhosis with hepatic lipid deposits (triglycerides), a condition also characteristically induced in cholesterol-fed animals which develop lipid containing vascular lesions (atherosclerosis). (Mortimer and Stanbridge 1968), (Thompson et al 1983). Sporidesmin also induced vascular necrosis and thrombosis with large infarcts.

 

As in humans, the hyperlipidemia in sheep responds to treatment with cholestyramine. Hove and Wright (1969) have documented that casein, phosphopeptones and phosphoserine protected rats against the toxicity of sporidesmin. The casein (milk) protection correlates well with the observation in humans that a glass of skim milk taken daily reduces hyperlipidemia.

 

Cyclopiazonic Acid-Induced Hypercholesterolemia and Hyperuricemia

Cyclopiazonicacid induced hyperlipidemia associated with hyperuricemia in an animal model (Referenceto be added).

 It is also interesting that hyperlipidemia is associated with hyperuricemia in atherosclerotic patients as well as in gouty patients. There has never been an explanation for this unique association. Mycotoxins provides a more than reasonable explanation.

 

Penitrem-Induced Hypercholesteremia and Hyperuricemia

 

Penitrem A, a mycotoxin produced by several species of Penicillium was found to cause hyperuricemia and hypercholesterolemia in dogs of mixed breed (Hayes et al 1976).

Again, we see a single mycotoxin inducement of hypercholesterolemia and hyperuricemia. This is not an isolated finding for other mycotoxins induce similar findings.

 

Kojii Acid-Induced Hypercholesterolemia/Hypertriglyceridemia

Giroir et al (1991) in studying the toxicological effects induced by the administration of kojic acid in the diet of young male chickens observed a significant increase in the serum concentrations cholesterol and triglycerides.

 

Synergism of Mycotoxins

 

Aflatoxin and/or Rubatoxin-Induced Hyperlipidemia

Hayes and Williams (1978) documented hyperlipidemia as part of the toxicity of aflatoxin and rubratoxin administered individually or together to dogs.

 

Smith et al (1992) conducted toxicological evaluation of aflatoxin and cyclopiazonic acid in broiler chickens. They found that the toxicity of CPA was expressed through increased blood levels of both uric acid and cholesterol. They also demonstrated that the effects of aflatoxin and cyclopiazonic acid were additive indicating the existence of synergistic toxicity.

 

Given the varied nature of human dietary intake of mycotoxin-related foods, there is the obvious question raised as to what effect mycotoxin synergy would have on the development of complex lesions such as are found in the variable nature of the atherosclerotic plaques.

 

Ochratoxin and/or T-2 Toxin- Induced Hypercholesterolemia/Hypertriglyceridemia

 

Kubena et al (1989) have reported the synergistic effects of ochratoxin A and T2 toxin on broiler chickens. When ochratoxin and T2 toxin were studied singularly and in combination for their toxic effects on broiler chickens, a significant synergistic increase in the serum concentrations of cholesterol and triglycerides was noted.

Studies conducted by Bauer and his associates in Munich, members of our WHO Collaborating Center for Mycotoxins in Food, have shown that over 50% of German adults have sigificant amounts of ochratoxin in their blood. If that fact is not troublesome enough, the milk of some women breast-feeding their infants has been documented to contain significant amounts of ochratoxin. Additional studies are in progress.

 
 
 

Return Home
 
BOOK ORDER FORM