The protective effects of feeding on the hepatic ultrastructure of rats treated with hypoglycin

Brooks, Stanley E. H.; Audretsch, J J

doi:10.1002/path.1711040303

Cited by 6 publications

(5 citation statements)

References 23 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The ultrastructural changes observed in the liver after hypoglycin treatment confirm the previous reports by Brooks & Audretsch (1970, 1971a,b, 1975), although we cannot explain the apparent swelling of the mitochondrial matrix. The decrease in the number of peroxisomes was not reported by these authors.…”

Section: Ultrastructural Changessupporting

confidence: 80%

“…The administration of hypoglycaemic doses of hypoglycin caused ultrastructural changes in rat liver: gross swelling of mitochondria, loss of dense matrix granules and presence of autophagic vacuoles containing mitochondria (Brooks & Audretsch, 1970, 197 1a,b, 1975. In parallel with a study of the effects of hypoglycin on carbohydrate metabolism (L. Hue & H. S. A.…”

mentioning

confidence: 99%

See 1 more Smart Citation

Protection of rats by clofibrate against the hypoglycaemic and toxic effects of hypoglycin and pent-4-enoate. An ultrastructural and biochemical study

Hoof¹,

Hue²,

Vamecq³

et al. 1985

Biochemical Journal

View full text Add to dashboard Cite

An ultrastructural and biochemical study of the toxic and hypoglycaemic effects of hypoglycin and pent-4-enoate was made on the livers of normal and clofibrate-fed rats. Injection of hypoglycin to rats doubles (from 22% to 44%) the volume fraction of mitochondria and decreases (from 1.05% to 0.26%) the volume fraction of peroxisomes in hepatocytes. The fast-acting toxin pent-4-enoate causes few ultrastructural changes except for the accumulation of lipids. In male adult rats fed with 0.5% clofibrate in their diet for 1-2 months, the volume fraction occupied by peroxisomes and mitochondria in hepatocytes rose to 6.26% and 29.5% respectively. Clofibrate feeding apparently protected the animals against the toxic, hypoglycaemic and hypothermic effects of hypoglycin and of pent-4-enoate, and completely prevented the ultrastructural damage caused by hypoglycin. After hypoglycin administration, hepatic mitochondrial butyryl-CoA dehydrogenase activity was inhibited by more than 90% and, surprisingly, the activity of the peroxisomal enzymes studied was largely preserved. When hypoglycin was given to rats fed on a clofibrate-containing diet, the oxidation of decanoylcarnitine, which was incomplete after hypoglycin treatment alone, remained incomplete with uncoupled mitochondria, but became apparently complete with coupled mitochondria. In the latter condition, there was a slowing of the rate during the last quarter of the pulse of oxygen uptake. Further, butyryl-CoA dehydrogenase activity was much less affected by hypoglycin in clofibrate-fed animals. Pent-4-enoate does not inhibit beta-oxidation in coupled mitochondria from clofibrate-treated rats.

show abstract

Section: Ultrastructural Changessupporting

confidence: 80%

mentioning

confidence: 99%

Protection of rats by clofibrate against the hypoglycaemic and toxic effects of hypoglycin and pent-4-enoate. An ultrastructural and biochemical study

Hoof¹,

Hue²,

Vamecq³

et al. 1985

Biochemical Journal

View full text Add to dashboard Cite

show abstract

“…Apart from hyaline, granular, or myoglobin-containing cylinders in the tubules of the kidney, the parenchymatous organs showed no histological abnormalities [27,28]. In rats, ultrastructural electron microscopic examination revealed swelling of the mitochondria of liver cells and a reduction in matrix density 3-5 h after intraperitoneal injection of a high HGA dose (i.e., 100 mg/kg; [33]).…”

Section: Introductionmentioning

confidence: 98%

Tissue Specific Distribution and Activation of Sapindaceae Toxins in Horses Suffering from Atypical Myopathy

Sander

Terhardt

Janzen

et al. 2023

Animals

View full text Add to dashboard Cite

Equine atypical myopathy is caused by hypoglycin A (HGA) and methylenecyclopropylglycine (MCPrG), the known protoxins of sycamore maple (Acer pseudoplatanus). Various tissues from five atypical myopathy cases were analyzed but only HGA was found. Whether deamination of MCPrG has already occurred in the intestine as the first stage of metabolization has not been investigated. Activation of the protoxins to methylenecyclopropylacetyl (MCPA)-CoA and methylenecyclopropylformyl (MCPF)-CoA, respectively, occurred mainly in the skeletal muscles, as evidenced by very high concentrations of MCPA-carnitine and MCPF-carnitine in this tissue. Inhibition of the acyl-CoA dehydrogenases of short- and medium-chain as well as branched-chain fatty acids by the toxins led to a strong increase in the corresponding acylcarnitines, again preferentially in skeletal muscles. An accumulation of the long-chain acylcarnitines beyond the level of the control samples could not be detected in the tissues. As a high amount of HGA was always found unmetabolized in the organs, we speculate that targeting the interruption of further metabolization might be a way to stop the progression of intoxication. Inhibition of the mitochondrial branched-chain amino acid aminotransferase, i.e., the first enzyme responsible for the activation of sycamore maple protoxins, could be a therapeutic approach.

show abstract

“…Is it worthless to recommend to provide additional food to prevent atypical myopathy? Extrapolation of the results from studies performed on laboratory animals to horses must always been performed with caution but a protective effect associated with feeding has been demonstrated in rats poisoned with HGA (Brooks and Audretsch ). Complementary feed may contain vitamins and antioxidants that have been identified as the only therapeutics to be beneficial for survival (Van Galen et al .…”

mentioning

confidence: 99%

“…It is interesting to note that even in experimental rats (i.e. highly standardised laboratory animals) receiving exactly the same food ad libitum, the protective effect of feeding against the effects of HGA is variable (Brooks and Audretsch ).…”

mentioning

confidence: 99%

Analysing hypoglycin A, methylenecyclopropylacetic acid conjugates and acylcarnitines in blood to confirm the diagnosis and improve our understanding of atypical myopathy

Votion

2016

Equine Veterinary Education

View full text Add to dashboard Cite

Summary Owing to recent methodological validation studies, we have now the opportunity to determine hypoglycin A, methylenecyclopropylacetic acid–carnitine and acylcarnitines concentrations in equine serum. These analytes are essential to confirm the diagnosis of atypical myopathy but also to improve our understanding of the pathophysiology of the disease. In particular, they might help elucidate why some horses seem more resistant to hypoglycin A poisoning.

show abstract

The protective effects of feeding on the hepatic ultrastructure of rats treated with hypoglycin

Cited by 6 publications

References 23 publications

Protection of rats by clofibrate against the hypoglycaemic and toxic effects of hypoglycin and pent-4-enoate. An ultrastructural and biochemical study

Protection of rats by clofibrate against the hypoglycaemic and toxic effects of hypoglycin and pent-4-enoate. An ultrastructural and biochemical study

Tissue Specific Distribution and Activation of Sapindaceae Toxins in Horses Suffering from Atypical Myopathy

Analysing hypoglycin A, methylenecyclopropylacetic acid conjugates and acylcarnitines in blood to confirm the diagnosis and improve our understanding of atypical myopathy

Contact Info

Product

Resources

About