毒理性
研究了局部应用戊酸对小鼠表皮渗透屏障功能的影响，并将其与胆固醇进行了比较。用丙酮进行局部治疗导致经表皮水分丢失呈线性增加，与治疗次数成比例，在老年小鼠中比年轻小鼠更快。在老年小鼠表皮上施用戊酸增强了其对损伤的抵抗力以及从急性屏障破坏中恢复屏障功能的速率。相比之下，尽管胆固醇也有同样的效果，但所需的量比戊酸高得多。在年轻小鼠中，戊酸和胆固醇对抵抗丙酮损伤的能力以及从丙酮损伤中恢复的速率都没有影响。在局部施用戊酸的小鼠皮肤中，观察到胆固醇合成和3-羟基-3-甲基戊二酸辅酶A还原酶活性的刺激，而等摩尔胆固醇的刺激则没有看到。这些数据表明，局部应用戊酸增强了老年小鼠的屏障恢复能力，这不仅伴随着从戊酸加速胆固醇合成，而且还刺激了整个胆固醇生物合成。
... The effect of topical mevalonic acid on the murine epidermal permeability barrier function /was investigated/, comparing it with that of cholesterol. Topical treatment with acetone caused linear increases in transepidermal water loss, in proportion to the number of treatments more rapidly in aged mice than in young mice. Administration of mevalonic acid on aged murine epidermis enhanced its resistance against damage and the recovery rate of barrier function from acute barrier disruption. In contrast, although cholesterol also had the same effect, it required a much higher amount than mevalonic acid. In young mice, neither mevalonic acid nor cholesterol had any effect on resistance against acetone damage nor the recovery rate from acetone damage. In the skin of mice topically administered with mevalonic acid, stimulation of cholesterol synthesis and 3-hydroxy-3-methylglutaryl coenzyme A reductase activity were both observed, whereas none was seen with stimulation by equimolar cholesterol. These data indicate that a topical application of mevalonic acid enhances barrier recovery in aged mice, which is accompanied by not only acceleration of cholesterol synthesis from mevalonic acid but also stimulation of the whole cholesterol biosynthesis.
来源:Hazardous Substances Data Bank (HSDB)
