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首页> 外文期刊>Life sciences >BIOCHEMICAL ALTERATIONS IN GUINEA PIG ADRENAL CORTEX FOLLOWING ADMINISTRATION OF PD 132301-2, AN INHIBITOR OF ACYL-COA-CHOLESTEROL ACYLTRANSFERASE
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BIOCHEMICAL ALTERATIONS IN GUINEA PIG ADRENAL CORTEX FOLLOWING ADMINISTRATION OF PD 132301-2, AN INHIBITOR OF ACYL-COA-CHOLESTEROL ACYLTRANSFERASE

机译：在PD 132301-2（一种抑制酰基-COA-胆固醇酰基转移酶的抑制剂）进行管理后的几内亚猪肾上腺皮质中的生物化学改变

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摘要

To assess whether previously reported ultrastructural alterations of adrenocortical mitochondria induced by the acyl-CoA:cholesterol acyltransferase (ACAT) inhibitor PD 132301-2 are accompanied by functional deficits in tissue energy stores, phosphorylated adenine nucleotide levels in guinea pig adrenal cortex were quantitated. Adrenals of male guinea pigs were obtained at 1, 2, 6, or 24 hours after oral administration of 100 mg/kg PD 132301-2 or 0.5 % methylcellulose vehicle. In treated animals, ATP levels and ATP/ADP ratios were decreased approximately 50 % with concurrent increases in AMP. Calculated energy charge was also decreased; these decreases were maximal by 6 hours. Cholesterol esterification in adrenal cortex was inhibited, resulting in progressive accumulation of free cholesterol up to 3-fold over control by 24 hours, consistent with the ACAT inhibitory activity of the drug. These data suggest that PD 132301-2 distributes to the adrenal cortex where early alterations of tissue bioenergetics occur in a time frame consistent with ultrastructural alterations of mitochondria. [References: 7]
机译：为了评估先前报道的由酰基辅酶A：胆固醇酰基转移酶（ACAT）抑制剂PD 132301-2诱导的肾上腺皮质线粒体的超微结构改变是否伴随组织储能器的功能缺陷，对豚鼠肾上腺皮质中的磷酸化腺嘌呤核苷酸水平进行了定量。口服100 mg / kg PD 132301-2或0.5％甲基纤维素赋形剂后第1、2、6或24小时获得雄性豚鼠的肾上腺。在治疗的动物中，ATP水平和ATP / ADP比率随着AMP的增加而降低了约50％。计算出的能量电荷也减少了;这些减少在6小时内最大。肾上腺皮质中的胆固醇酯化被抑制，导致游离胆固醇的逐步积累到24小时比对照高3倍，与该药物的ACAT抑制活性一致。这些数据表明，PD 132301-2分布到肾上腺皮质，在那里组织生物能的早期改变发生在与线粒体超微结构改变相一致的时间范围内。 [参考：7]

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