Leonidov N B, Romanenko E B, Lebedev A V
Vopr Med Khim. 1995 Mar-Apr;41(2):32-5.
The effect of two methyluracil forms on the composition of lipids, the content of peroxidation products and the amount of lipid-soluble scavengers of free radicals was studied in rat liver and heart tissues. Both these forms caused an increase in content of total lipids in the animal liver tissue 2 hrs after injection, whereas beta-form increased 1.6-fold the content of cholesterol esters and 1.9-fold that of triglycerides in liver tissue, unlike the alpha-form which affected these parameters slightly. The effect of methyluracil polymorphic derivatives on lipid peroxidation (TBA-positive products) was not detected. The methyluracil beta-form, not affecting the total pool of hydrophobic antioxidants, was found to decrease the content of active scavengers of free radicals in rat liver and heart tissues, as well as beta-form decreased the content of vitamin E in these tissues. At the same time, the methyluracil alpha-form did not affect the composition of tissue hydrophobic antioxidants. These differences found in the effect of two methyluracil forms on lipid composition and lipid-soluble scavengers of free radicals may be responsible for biological nonequivalence of the drug polymorphic forms.
研究了两种甲基尿嘧啶形式对大鼠肝脏和心脏组织中脂质组成、过氧化产物含量以及脂溶性自由基清除剂含量的影响。注射后2小时，这两种形式均导致动物肝脏组织中总脂质含量增加，而β型使肝脏组织中胆固醇酯含量增加1.6倍，甘油三酯含量增加1.9倍，α型对这些参数影响较小。未检测到甲基尿嘧啶多晶型衍生物对脂质过氧化（TBA阳性产物）的影响。发现甲基尿嘧啶β型不影响疏水性抗氧化剂的总量，但会降低大鼠肝脏和心脏组织中自由基活性清除剂的含量，同时β型还会降低这些组织中维生素E的含量。与此同时，甲基尿嘧啶α型不影响组织疏水性抗氧化剂的组成。两种甲基尿嘧啶形式在脂质组成和脂溶性自由基清除剂方面的这些差异可能导致该药物多晶型形式的生物学不等效性。
