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ACTA Pharmaceutica Sciencia
2006 , Vol 48 , Num 2
BIOCHEMICAL, CYTOTOXIC AND GENOTOXIC EFFECTS OF A NOVEL NON-MERCAPTOPURINE IMMUNOSUPPRESSANT
Department of Pharmaceutical Technology, Irbid, Jordan
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Administration of MNITMT at a dose of 10 mg/kg for 35 days did not induce any significant change in various biochemical markers including serum alanine transferase, fasting blood glucose, total serum cholesterol and serum amylase. Moreover, MNITMT induced significant decrease in serum creatinine, serum albumin and total serum bilirubin and a significant increase of blood urea. The increased level of blood urea may be attributed to reduced protein biosynthesis and increased tissue wasting due to a possible inhibitory effect of the derivative on protein biosynthesis. MNITMT did not show any cytotoxicity when tested by the shrimp bioassay. However, MNITMT was a weak base-pair substitution mutagen in strain TA 100 of Salmonella typhimurium but induced no mutagenicity in TA 1535 strain. This compound did not have any frameshift mutagenic action in TA 98, TA 1537 or TA 1538 of Salmonella typhimurium strains when Ames test was used. The safety of this novel derivative as indicated by these preliminary studies as well as by the previous investigations encourages performing more detailed investigations to further confirm its efficacy and safety.
Keywords :
AZATHIOPRINE, CYTOTOXICITY, GENOTOXICITY, MUTAGENICITY, IMMUNOSUPPRESSANT ABBREVIATION: MNITMT (3-[1-METHYL-4-NITRO-1H-IMIDAZOL-5-YL) THIO]-4-METHYL-1, 2, 4-TRIAZOLE)
