Poster presentation, P3

Official XXIst International Pigment Cell Conference website - 21-24 Sept 2011, Bordeaux - France | updated: September 04 2011

Measurements of hydroxyl free radical-scavenging capacities of melanin-binding hydroxychloroquine using an electron spin resonance spectroscopy

OBJECTIVE: To determine the scavenging effects of melanin-binding hydroxychloroquine (HCQ) on transient hydroxyl free radical generated via the Fenton reaction, it is helpful in better understanding the mechanisms of antimalarials behind anti-inflammation and anti-photosensitivity. METHODS: Water-soluble bacteria-derived melanin was prepared from a tyrosinase-producing bacterium (Pseudomonas maltophilia AT 18). Transient hydroxyl free radical was generated via the Fenton reaction and trapped by DMPO. DMPO (400 mmol/L), ferrous sulfate (0.4 mmol/L), H2O2 (0.1%) and varying concentration of melanin-binding hydroxychloroquine were mixed and incubated, then sucked into a quartz capillary for 30 sec and measured by ESR. The relative amount of the radicals was estimated from the peak height of the second peak of the DMPO-OH signals in typical ESR spectra. RESULTS: The bacteria-derived melanin (b-melanin) ranging from 20 mg/L to 100 mg/L exhibited a potent scavenging action for hydroxyl free radical in a dose-dependent manner. 100 mg/L of b-melanin could afford a maximum scavenging activity (92.5%) of against hydroxyl free radical. HCQ showed a limited and dose-irrelevant scavenging activity toward hydroxyl radical. 50 µmol/L of HCQ had the highest scavenging rate (43.72%) against hydroxyl free radicals. The melanin bound with 10µmol/L HCQ, corresponding to the mean blood concentration of HCQ in SLE patients receiving 400 mg of HCQ daily, demonstrated an increased scavenging activity against the radicals to compare with that of HCQ alone (P<0.05). Elevated concentration of HCQ to bind with the melanin didn't increase their scavenging rate of hydroxyl free radical. CONCLUSION: The melanin achieves an enhanced scavenging activity on hydroxyl free radical by binding with HCQ at the physiological concentration (10µmol/L HCQ), by which protects the skin cells from oxidative damages and likely contributes to anti-photosensitivity of antimalarials in the treatment of cutaneous lupus erythematosus.

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