Metabolic response of diacetoxyscirpenol treated mice to vitamin A

Abstract

Diacetoxyscirpenol (DAS) is a trichothecene produced by Fusarium species. DAS is cytotoxic to the rapid dividing cells. Vitamin A is essential for cell growth and cysteine has been used to antagonize effect of some chemicals. This study is conducted to determine the effect of DAS is Swiss mice and to see whether vitamin A pretreatment or cystein plus vitamin A pretreatment has any influences on the effect of DAS. There were no difference in hemoglobin, hematocrit, red blood cell, reticulocyte, platelet and bone marrow cell count of control and DAS treated at 5, 10 mg/KgBW IP for 1,6 hr. White blood cell particularly neutrophil and lymphocyte were elevated in DAS 10 mg/kgBW while the spleen weight was reduced. The hematological change after one dose of DAS 10 mg/KgBW IP were more obvious at 48-72 hr. Spleen, thymus and testes weight were reduced during the first 4 days and back to normal in 7 days. Alterations were observed in the germinal and interstitial cells of testes. DAS 20 mg/KgBW IP caused a decrease in DNA and RNA of thetes. Hemoglobin, hematocrit, white blood cell, red blood cell count, bone marrow cell, reticulocyte were lower than control. Female was more sensitive than male mice. DAS 15 mg/KgBW IP 48 hr did reduce reticulocyte, white blood cell, testes, thymus and spleen weight, DNA, RNA, protein content of testes, and serum testosterone. No change in prostatic acid phosphatase was observed. DAS 10 mg/KgBW IP 24 hr was set up to study chromosomal damage due to DAS by using cyclophosphamide 40 mg/KgBW as a positive control. It was found that DAS caused changes on the proliferation of bone marrow cellular, therefore it was impossible to demonstrate the alteration on the chromosome by using micronucleus test. Retinyl acetate 1,000 µg/day P.O. for three consecutive days prior to DAS 5 mg/KgBW increased the hemoglobin content, red blood cell, reticulocyte and bone marrow cell count when compared to the non vit A pretreated groups. Vitamin A improve the myeloid cell especially lymphoblast and myelocyte in bone marrow smear. Macrophage was increase more obvious in DAS 10 mg/KgBW than DAS 5 mg/KgBW. The morphology of spermatocyte in vitamin A pretreated mice was well differentiated than in DAS alone. Treatment of cystein 1211.6 mg/KgBW 3 days before vitamin A 1,000 ..g/day and DAS 5 mg/KgBW had slightly higher hemoglobin, hematocrit, red blood cell cound, and white blood cell count than vitamin A plus DAS at 24 hr after administration. Manakaryocyte in mice treated vitamin A or cysteins was higher than DAS. Therefore, it is suggested that vitamin A pretreatment alone or cysteine plus vitamin A may give a better picture than DAS in some paremeters.