Tissue reparation histology of open cutaneous wonds by metotrexate: experimental studies of female rats
DOI:
https://doi.org/10.32635/2176-9745.RBC.1996v42n1.2885Keywords:
Skin, Wound Healing, Histology, Methotrexate, Drug EffectsAbstract
The authors have studied the action of methotrexate applied intramusculary on healing of cutaneous circular open wound on female ratsfrom the macroscopic and histological point of view. 36 Wistar female rats scaling 250.0 grams on an average. On the 18 animais of the control group (Group 1) sodium chloride was injected intramuscularly into the left back member in an equivalent to the amount required for the group treated, immediately after making a skin open wound with a 6 mm diameter punch on the back of the animal at about 5 cm from the lower edges of the external ears. The same surgical procedure of the control group was carried out in the experimental group (Group 2), and methotrexate (1 mg/kg ofbody weight) was applied intramuscularly into the same anatomic location. They were killed on the 4th and 7th days after operation. The histologic alterations ofthe ejfect of methotrexate evidenced through optical microscopy, such as reduction of tissue area of granulation and necrosis (p < 0.001), the number of round nuclei (p < 0.001), in the number of fibroblasts and histiocytes in transformation (fusiform nuclei field) (p < 0.001), in the distance getween the edges of the wound (p < 0.001) and in the number of vessels/field (p < 0.05), were predominant on the 4th and 7th days. It is concluded that, the methotrexate attenuates the inflammatory answer actuating in the initial and fibroplasia phases, however, this has accelerated the reepitelization process.
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References
Bender, R.A. - Membrane transport of methotrexate (NSC-740) in human neoplastic cells. Cancer Chemother Rep, 6(Part3): 73-82, 1975.
Bleyer, W.A. - The clinical pharmacology of methotrexate: new applications of an old drug. Cancer, 41: 36-51, 1978. DOI: https://doi.org/10.1002/1097-0142(197801)41:1<36::AID-CNCR2820410108>3.0.CO;2-I
Calabresi, P, Parks Jr., R.E. - Quimioterapia das doenças neoplásicas. In: Gilman, A.G.; Goodman, L.S.; Rali, T.W.; Murad, F. (Eds.). As Bases Farmacológicas da Terapêutica. T ed. Rio de Janeiro, Guanabara Koogan, 813-56, 1987.
Calnan, J.; Davies, A. - The effect of methotrexate (amethopterin) on wound healing: an experimental study. Br J Cancer, 19: 505-12, 1965. DOI: https://doi.org/10.1038/bjc.1965.61
Campbell, M.A.; Perrier, D.G.; Dorr, R.T. - Methotrexate: bioavaulability and pharmacokinetics. Cancer Treat Rep, 69: 833-8, 1985.
Campos, H. - Estatística Experimental não Paramétrica. 4ª ed., Piracicaba, SP, Departamento de Matemática e Estatística, ESALQ, USP, 1983.
Carneiro, P.C.A. - Efeito da Quimioterapia Antineoplásica com Cisplatina (cisdiaminodicloroplatina-II) na Cicatrização de Anastomoses do Intestino Delgado: Estudo Experimental em Ratos. Rio de Janeiro, UFRJ, 140,1990. (Tese-Doutorado-Faculdade de Medicina-Universidade Federal do Rio de Janeiro).
Carneiro, P.C.A. - Aspectos Macroscópicos e Histológicos da Reparação Tecidual de Feridas Cutâneas Abertas sob Efeito de Quimioterapia com Metotrexato: Estudo Experimental em Ratas. Rio de Janeiro, UGF, 75, 1992. (Tese Livre Docência - Universidade Gama Filho).
Cohen, S.C.; Gabelnick, H.L.; Johnson, R.K.; Goldin, A. - Effects of cyclophosphamide and adriamycin on the healing of surgical wounds in mice. Cancer, 36: 1277-81, 1975. DOI: https://doi.org/10.1002/1097-0142(197510)36:4<1277::AID-CNCR2820360413>3.0.CO;2-1
Desesso, J.M.; Goering, G.G. - Amelioration by leucovorin of methotrexate development toxicity in rabbits. Teratology43: 201-15, 1991. DOI: https://doi.org/10.1002/tera.1420430304
Desprez, J.D., Kiehn, C.L. - The effect of cytoxan (cyclophosphamide) on wound heaXing. Plast Reconstr Surg, 26: 301-8, 1960. DOI: https://doi.org/10.1097/00006534-196009000-00005
Evans, W.E.; Christensen, M.L. – Drug intercations with methotrexate. J Rheumatol, 12 (Suppl 12): 15-20, 1985.
Ferguson, M.K. - The effect of antineoplastic agents on wound healing. Surg GYnecol Obstet 154: 421-9, 1982.
Freeman-Narrod, M.; Gerstley, B.J.; Engstrom, P.F. - Comparison of sérum concentrations of methotrexate after various route of administration. Cancer, 36: 1619-24, 1975. DOI: https://doi.org/10.1002/1097-0142(197511)36:5<1619::AID-CNCR2820360514>3.0.CO;2-G
Hardesty, W.H. - The effect of cytotoxic drugs on wound healing in rats. Cancer Res, 18: 581-4, 1985.
Hoff, M.B.; Chang, W.W.L.; Mak, K.M. - Effect of estrogen on cell-proliferation in colonic mucosa of the mouse, VirchowsArch (CellPathol), 35:263-73, 1981. DOI: https://doi.org/10.1007/BF02889166
Hughes, G.R.; Abdulla, M. - Methotrexate treatment of Felty’s syndrome (letter). Ann Rheum Dis, 49: 202, 1990. DOI: https://doi.org/10.1136/ard.49.3.202-b
Jeurissen, M.E.C.; Boerbooms, A.M.T.; Van de Puttle, L.B.A. – Methotrexate therapy in connective tissue diseases: a review of the literature. Netherlands J Med, 35: 44-58, 1989.
Jolivet, J.; Cowan, K.H.; Curt, G. A. – The pharmacology and clinicai use of methotrexate. N Engl J Med 309: 1094-104, 1983. DOI: https://doi.org/10.1056/NEJM198311033091805
Kaiser, G.A.; Herter, F.P.; Malm, J.R.; Demetz, A.; Campione, M.P. - Effects of chemotherapeutics agents administered by isolated perfusion upon wound healing. Surgery, 49: 745-50, 1961.
McMurry Jr., J.F. - Wound healing with diabetes mellitus: better wound healing in diabetes. Surg Clin North Am, 64: 769-78, 1984. DOI: https://doi.org/10.1016/S0039-6109(16)43393-1
Mitchell, M.S.; Wade, M.E.; DeConti, R.C.; Bertino, J.R.; Calabresl, P. - Immunosuppressive effects of cytosine arabinoside and methotrexate in man. Ann Intern Med, 70: 535-40, 1969. DOI: https://doi.org/10.7326/0003-4819-70-3-535
Modolin, M.; Bevilacqua, R.G.; Margarido, N.F.; Lima-Gonçalves, E. – Effects of protein depletion and repletion on experimental open wound contraction. Ann PlastSurg, 15: 123-6, 1985. DOI: https://doi.org/10.1097/00000637-198508000-00005
Newcome, J.F.; Chir, M. - Effect of Intra-arterial nitrogen mustard infusion on wound healing in rabbits: formation of granulation tissue and wound contraction. Ann Surg, 163: 319-29, 1966. DOI: https://doi.org/10.1097/00000658-196603000-00001
Pimentel-Gomes, F. - Curso de Estatística Experimental. 12ª ed. Rio de Janeiro, Livraria Nobel, 467, 1989.
Shamberger, R.C.; Devereux, D.F.; Brennan, M.F. - The effect of chemotherapeutic agents an wound healing. Int Adv Surg Oncol, 4: 15-58, 1981.
Shiner, R.J.; Nunn, A.J.; Chung, K.F.; Geddes, D.M. - Randomised doubleblind, lacebo-controlled trial of methotrexate in steroid-dependent asthma. Lancet, 336: 137-40, 1990. DOI: https://doi.org/10.1016/0140-6736(90)91659-X
Simões, M. de J.; Cabral, A.C.V.; Boyaciyan, K.; Kulay Júnior, L.; Sasso, W.S - Aspectos ultra-estruturais dos fibroblastos e dos macrófagos durante o processo de reperação de pele de ratos. Rev Paul Med, 104: 1986; 132-5.
Stern, R.S.; Zierler, S.; Parrisch, J.A. - Methotrexate used for psoriase and the risk of moncutaneous or cutaneous malignancy. Cancer, 50: 869-72, 1982. DOI: https://doi.org/10.1002/1097-0142(19820901)50:5<869::AID-CNCR2820500511>3.0.CO;2-V
Suarez, C.R.; Pickett, W.C.; Bell, D.H.; McLintock, D.K.; Oronsky, A.L.; Kerwar, S.S. - Effect on low dose methotrexate on neutrophil chemotaxis induced by leukotriene B4 and complement C5a. J Rheumatol. 14: 9-n, 192,1.
Vokes, E.E.; Dimery, I.W.; Jacobs, C.D.; Karp, D.; Molina, A.; Collier, M.A.; Eble, M.L.; Clendeninn, N.J. - A phase II study of piritrexim in combination with methotrexate in recurrent and metastatic head and neck cancer. Cancer, 67:2253-7, 1991. DOI: https://doi.org/10.1002/1097-0142(19910501)67:9<2253::AID-CNCR2820670907>3.0.CO;2-Y
Wang, Y.M.; Stuow, W.W.; Romsdahl, M.M. - Age-related pharmacokinetics of high-dose methotrexate in patients with osteosarcoma. Cancer Treat Rep, 63: 405-10, 1979.
