Biomaterial Database

Experimental study on subacute neurotoxicity of methotrexate in cats. 1989

M Shibutani, and R Okeda

Department of Pathology, Tokyo Medical and Dental University, Japan.

An experimental study on the pathogenesis of methotrexate (MTX)-related neurotoxicity including disseminated necrotizing leukoencephalopathy (DNL) was conducted in cats. MTX was administered to the cerebrospinal fluid (CSF) of adult cats using either an intracisternal intermittent instillation (ICI) model or an intraventricular continuous instillation (IVC) model. Furthermore, the synergistic effects of CSF-flow disturbance with kaolin-induced hydrocephalus, and 60Co irradiation were morphologically examined in these models. None of the animals from either the ICI and IVC groups showed DNL, but all animals showed segmental axonal degeneration, suggesting that MTX had a direct toxic effect on the axon. In the ICI groups, no apparent synergistic effect of CSF-flow disturbance and radiation was noted on this axonal change. In the IVC groups, CSF-flow disturbance augmented the degree of the axonal injury. Axonal degeneration and fibrin exudation in the walls of small blood vessels occurred in one animal of the IVC groups with CSF-flow disturbance, suggesting that a toxic effect of MTX on blood vessels is another mechanism of MTX-induced neurotoxicity.

UI	MeSH Term	Description	Entries
D008297	Male		Males
D008727	Methotrexate	An antineoplastic antimetabolite with immunosuppressant properties. It is an inhibitor of TETRAHYDROFOLATE DEHYDROGENASE and prevents the formation of tetrahydrofolate, necessary for synthesis of thymidylate, an essential component of DNA.	Amethopterin,Methotrexate Hydrate,Methotrexate Sodium,Methotrexate, (D)-Isomer,Methotrexate, (DL)-Isomer,Methotrexate, Dicesium Salt,Methotrexate, Disodium Salt,Methotrexate, Sodium Salt,Mexate,Dicesium Salt Methotrexate,Hydrate, Methotrexate,Sodium, Methotrexate
D009336	Necrosis	The death of cells in an organ or tissue due to disease, injury or failure of the blood supply.
D009498	Neurotoxins	Toxic substances from microorganisms, plants or animals that interfere with the functions of the nervous system. Most venoms contain neurotoxic substances. Myotoxins are included in this concept.	Alpha-Neurotoxin,Excitatory Neurotoxin,Excitotoxins,Myotoxin,Myotoxins,Neurotoxin,Alpha-Neurotoxins,Excitatory Neurotoxins,Excitotoxin,Alpha Neurotoxin,Alpha Neurotoxins,Neurotoxin, Excitatory,Neurotoxins, Excitatory
D002415	Cats	The domestic cat, Felis catus, of the carnivore family FELIDAE, comprising over 30 different breeds. The domestic cat is descended primarily from the wild cat of Africa and extreme southwestern Asia. Though probably present in towns in Palestine as long ago as 7000 years, actual domestication occurred in Egypt about 4000 years ago. (From Walker's Mammals of the World, 6th ed, p801)	Felis catus,Felis domesticus,Domestic Cats,Felis domestica,Felis sylvestris catus,Cat,Cat, Domestic,Cats, Domestic,Domestic Cat
D002555	Cerebrospinal Fluid	A watery fluid that is continuously produced in the CHOROID PLEXUS and circulates around the surface of the BRAIN; SPINAL CORD; and in the CEREBRAL VENTRICLES.	Cerebro Spinal Fluid,Cerebro Spinal Fluids,Cerebrospinal Fluids,Fluid, Cerebro Spinal,Fluid, Cerebrospinal,Fluids, Cerebro Spinal,Fluids, Cerebrospinal,Spinal Fluid, Cerebro,Spinal Fluids, Cerebro
D003711	Demyelinating Diseases	Diseases characterized by loss or dysfunction of myelin in the central or peripheral nervous system.	Clinically Isolated CNS Demyelinating Syndrome,Clinically Isolated Syndrome, CNS Demyelinating,Demyelinating Disorders,Demyelination,Demyelinating Disease,Demyelinating Disorder,Demyelinations
D004195	Disease Models, Animal	Naturally-occurring or experimentally-induced animal diseases with pathological processes analogous to human diseases.	Animal Disease Model,Animal Disease Models,Disease Model, Animal
D004357	Drug Synergism	The action of a drug in promoting or enhancing the effectiveness of another drug.	Drug Potentiation,Drug Augmentation,Augmentation, Drug,Augmentations, Drug,Drug Augmentations,Drug Potentiations,Drug Synergisms,Potentiation, Drug,Potentiations, Drug,Synergism, Drug,Synergisms, Drug
D005260	Female		Females