Ward B J, Breathnach A S, Robins E J, Bhasin Y P, Ethridge L, Nazzaro-Porro M, Passi S
J Invest Dermatol. 1986 Apr;86(4):438-41. doi: 10.1111/1523-1747.ep12285783.
The cytotoxic effect of azelaic acid on murine melanoma cells in culture is due, at least in part, to an antimitochondrial action. We investigated the possibility that the addition of carnitine to the medium may increase the transport of azelaic acid into the mitochondria and thereby increase its cytotoxic effect. Using mitochondrial cross-sectional area measured from electron micrographs as a criterion for mitochondrial damage, we found that the addition of L-carnitine to the culture medium had no effect either alone or with a low (10(-3) M) concentration of azelaic acid. At a high concentration (5 X 10(-2) M) azelaic acid caused swelling and disruption of the mitochondria to such an extent that this was not increased by carnitine. At 10(-2) M azelaic acid, however, some swelling of the mitochondria occurred which was significantly increased by the addition of carnitine. This indicates that carnitine-mediated transport of the diacid into the mitochondria had occurred. We conclude that carnitine may reduce the time or concentration needed for azelaic acid to have a toxic effect on the malignant melanocyte.
壬二酸对培养的鼠黑色素瘤细胞的细胞毒性作用至少部分归因于抗线粒体作用。我们研究了在培养基中添加肉碱可能会增加壬二酸进入线粒体的转运从而增强其细胞毒性作用的可能性。以从电子显微镜照片测量的线粒体横截面积作为线粒体损伤的标准,我们发现向培养基中单独添加L -肉碱或与低浓度(10⁻³ M)的壬二酸一起添加均无效果。在高浓度(5×10⁻² M)时,壬二酸会导致线粒体肿胀和破坏,以至于肉碱不会使其进一步加剧。然而,在10⁻² M的壬二酸浓度下,线粒体出现了一些肿胀,添加肉碱后肿胀明显增加。这表明已发生肉碱介导的二酸转运进入线粒体。我们得出结论,肉碱可能会减少壬二酸对恶性黑素细胞产生毒性作用所需的时间或浓度。