COMPARATIVE EVALUATION OF
METHOTREXATE TOXICITY AS SOLUTION
FOR INJECTION AND LIPOSOMES
FOLLOWING A SHORT-TERM TREATMENT IN
A MURINE MODEL OF ARTHRITIS: NOTE II.
HISTOPATHOLOGICAL CHANGES
MARIA BÂRCĂ1, DANIELA LUIZA BACONI 1*, ANNE-MARIE
CIOBANU1, MANUELA MILITARU2, GEORGE TRAIAN
ALEXANDRU BURCEA1, CRISTIAN BĂLĂLĂU3
1University of Medicine and Pharmacy “Carol Davila”, Faculty of
Pharmacy, Traian Vuia 6, Bucharest, Romania
2 University of Agronomic Science and Veterinary Medicine, Faculty
of Veterinary Medicine, Splaiul Independentei 105, Bucharest,
Romania,
3University of Medicine and Pharmacy “Carol Davila”, Faculty of
Medicine, Sf. Pantelimon Emergency Hospital, Sos Pantelimon 340 –
342, Bucharest, Romania
*corresponding author: daniela_baconi@yahoo.com
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Abstract:

The aim of this study was the evaluation of the histopathological changes
induced by methotrexate (MTX)-loaded liposomes, comparatively with MTX injectable solution, following a short-term treatment in a rat model of arthritis (adjuvant Freund induced).
Liposomes with MTX itself ("hydrophobic MTX") and with its disodium salt
("hydrosoluble MTX") have been prepared.
Three different doses of MTX preparations have been intravenously (i.v.)
administered, at three doses (0.2 mg/kg b.w., 0.3 mg/kg b.w. and 0.4 mg/kg b.w.), once a week for three weeks. The toxicity of MTX was evaluated in terms of histopathological changes in the liver and kidney.
Histopathological observations revealed more pronounced changes in the
kidney, comparatively with the liver. Slight changes in the liver were observed in animals treated with hydro-soluble or hydrophobic MTX-loaded liposomes, (moderate and irregular granular dystrophy, discrete mononuclear cell infiltration, and moderate stasis in centro lobular veins), which were not significantly influenced by the type of treatment. The treatment with MTX solution for injection caused the same type of
changes, but more pronounced (higher intensity of the dystrophic process, micro-focal points of mononuclear cells infiltrations, moderate steatosis).
Glomerullar stases, the increase of the vascular network volume, tubular
nephritis and medullary mononuclear cell infiltration have been revealed in the kidney.
Short-term treatment with MTX-loaded liposomes or MTX solution for
injection in rats with an inflammatory process of arthritis type, did not induce
ireversible histopathological changes in the liver or kidney.The results of histopathological examinations indicated reduced toxic effects of MTX in the dosage range administered in this study.






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