Acute encephalopathy with hepatic steatosis induced by pantothenic acid antagonist, calcium hopantenate, in dogs
Abstract
In Japan, acute encephalopathy with hepatic steatosis resembling Reye's syndrome has been reported to occur after treatment with the pantothenic acid antagonist, calcium hopantenate. We studied the causal relationship and the pathogenesis in dogs. The agent was administered to seven dogs at increasing doses over a period of 8 weeks. Anorexia, vomiting, and diarrhea were common clinical findings. In four dogs, coma suddenly developed after the appearance of gastrointestinal signs. Three animals died during periods when they were not under direct observation. The effects of the agent appear to be related to dose. Laboratory findings representing significant changes at the time of coma included hypoglycemia, leukocytosis, hyperammonemia, hyperlactatemia, and elevated levels of serum transaminases. Microvesicular hepatic steatosis and mitochondrial abnormalities were consistent pathological findings. The hepatic mitochondria were enlarged and characterized by an increased number of cristae and the presence of crystalloid inclusions. In a second group of four dogs, pantothenic acid was given in addition to and in the same amount as calcium hopantenate at increasing doses over a period of 8 weeks. All four dogs survived the 8 weeks and only one developed mild anorexia. No significant biochemical changes were found and neither hepatic steatosis nor mitochondrial abnormalities were observed. The addition of pantothenic acid prevented the development of the disorder in the four animals. These results show that calcium hopantenate produces acute encephalopathy with hepatic steatosis in dogs, by inducing a deficiency of pantothenic acid. The hepatic mitochondrial changes of this reaction differ from those of Reye's syndrome.
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Pantothenic acid deficiency results in neurological dysfunction, including acute encephalopathy in dogs and personality changes in humans.
“Deficiency in pantothenic acid (vitamin B5) results in neurological dysfunction. Dogs treated with an antagonist of vitamin B5 that induces a deficiency of pantothenic acid developed an acute encephalopathy [144].”
From Vitamins and Minerals for Energy, Fatigue and Cognition: A Narrative Review of the Biochemical and Clinical Evidence (2020) · cites this paper as [144]
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Tardy, A.-L., Pouteau, E., Marquez, D., Yilmaz, C., & Scholey, A. (2020) · Nutrients · doi:10.3390/nu12010228 · Cited by 541 · see citing works
- Authors
- Noda, S., Haratake, J., Sasaki, A., Ishii, N., Umezaki, H., & Horie, A.
- Affiliations
- University of Occupational and Environmental Health Japan (JP)
- Corresponding author
- Noda, Shousaku
- ORCID
- Ishii, Nobuyoshi
- Venue
- Liver
- Publisher
- Wiley
- Published
- 1991-06
- Volume
- 11
- Issue
- 3
- Pages
- 134-142
- ISSN
- 0106-9543 (ISSN-L)
- 1600-0676
- OpenAlex
- W2069342913
- Cited by
- 17
- References
- 15
- Citations by year
- 2021: 2 · 2020: 2 · 2016: 1 · 2015: 2 · 2013: 1 · 2012: 1
- FWCI
- 0.00
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Liver International (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmacology › Drug-Induced Hepatotoxicity and Protection
- Life Sciences › Neuroscience › Neurology › Neurological diseases and metabolism
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Clinical Biochemistry › Metabolism and Genetic Disorders
- Keywords
- acute encephalopathy, hepatic steatosis, Reye's syndrome, pantothenic acid deficiency, mitochondrial abnormalities, microvesicular steatosis, drug-induced encephalopathy, dogs, dose-dependent toxicity
- MeSH terms
- Acute Disease, Animals, Brain Diseases, Dogs, Fatty Liver, Female, gamma-Aminobutyric Acid, Liver, Male, Microscopy, Electron, Mitochondria, Liver, Pantothenic Acid
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