Aminoglycoside 계열 항생제 tobramycin의 멜라닌 생성 증진 효과

Abstract

Since the first antibiotic, penicillin, the era of antibiotics has opened and many new antibiotics have been discovered and developed. However, in the 21st century, antibiotics discovered in the 20th century have been gradually reduced in usage or are no longer used due to antibiotic resistance, side effects, and the development of more effective antibiotics. In this study, we investigated the effects of streptomycin, kanamycin A, kanamycin B, tobramycin, fradiomycin, paromomycin, spertinomycin, hygromycin B, gentamicin, fosfomycin and lincomycin on melanogenesis in B16F10 melanoma cells. First, the effect of each antibiotic on the survival of B16F10 cells was confirmed by MTT assay. Subsequently, the groups of antibiotic alone treatment and the groups treated with antibiotics and α-MSH in the non-toxic concentration were divided to evaluate the effect on melanogenesis. Melanin production was decreased in kanamycin A and streptomycin, and melanin production was increased in tobramycin, fosfomycin and lincomycin. Melanin production was not changed in kanamycin B, fadomycin, paromomycin, spectinomycin, hygromycin B and gentamicin. Among them, melanin contents assay and tyrosinase activity assay were further performed with tobramycin, which increased melanin production remarkably. It was confirmed that tobramycin increased melanin production and increased the activity of tyrosinase, an enzyme important for melanin synthesis. We also confirmed that tobramycin phosphorylates p38, one of the MAPK proteins, by using western blotting and inhibitors, thereby increasing the expression of MITF protein. The increased expression of MITF increased the expressions of tyrosinase, TRP-1, TRP-2, an enzyme important for the synthesis of melanin, in a dose-dependent manner. We compared the effects of kanamycin A, kanamycin B with similar structure to tobramycin and 2-DOS, the central structure of these on the synthesis of melanin. As a result, the effect of tobramycin on the synthesis of melanin was presumed to be the structure of the aminosugar attached to the C-4 of 2-DOS, the central skeleton. Since melanocytes are mainly in the skin layer, the effect of tobramycin on keratinocytes was evaluated. At a concentration of 2 mg/mL, cell viability was over 90 %. In addition, the effect of RAW 264.7 cells on NO production, an inflammatory substance, was evaluated but not effective. Based on these results, we suggest that tobramycin may be helpful in the treatment of hypopigmentation.