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Death by MBEH

Monobenzyl ether of hydroquinone (MBEH) (aka monobenzone) is currently the sole FDA- approved drug for depigmentation of vitiligo patients; however, very little is known about its working mechanism. In order to improve future depigmentation treatments, it is important to know if MBEH specifically targets melanocytes, and whether it reduces pigment production or kills melanocytes. Our studies reveal that MBEH specifically targets melanocytes when applied to the skin. If ingested, however, it may kill other cell types and lose its specificity.The fate of melanocytes in response to MBEH was examined to determine the mode of death.

  • Apoptosis is a highly regulated programmed cell death which helps to minimize debris.
  • Necrosis, on the other hand, is an uncontrolled cell death due to a sudden traumatic event.

The mode of cell death is a determining factor for subsequent immune system activation. In the case of apoptosis, dying cells are digested completely, with no inflammatory response. However, necrotic cells spill their cellular contents, requiring their removal, so inflammatory cells are called for this job. This response in MBEH can/could indirectly trigger a specific immune response to melanocytes, resulting in extended vitiligo.

Prior studies have shown that 4-tertiary butyl phenol (4-TBP), held responsible for occupational vitiligo, induces apoptosis in melanocytes. MBEH was expected to do the same. Surprisingly, MBEH clearly induces necrotic melanocyte death. Thus, skin application of MBEH in one site may activate an immune response that supports elimination of melanocytes elsewhere, explaining depigmentation observed in areas away from the application site.

MBEH application is prescribed to patients of different skin tones, so it is important to understand whether pigmentation levels affect the depigmentation process. Studies conducted to correlate skin tone with respective melanocyte sensitivity upon MBEH exposure suggested that melanin can offer protection against MBEH-induced cell death. Therefore, the depigmentation process using MBEH in people with a darker skin tone could possibly take more persistence.These studies are helpful to assist in the future design of custom depigmentation therapy, and the data can also help us to consider alternative applications for bleaching agents.

VSI would like to thank Vidhya Hariharan, Graduate Program in Biochemistry, Loyola University Chicago for the contribution and Dr. Caroline Le Poole, Loyola University Chicago for the supervision of this article.

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