Photodermatoses are a group of dermatological diseases caused by hypersensitivity to UV band of the sunlight. Hypersensitivity of skin to UV light may manifest itself as phototoxic or photoallergic reaction. Phototoxic reactions may be caused by a variety of drugs such as sulfonamides, tetracyclines, phenothiazines, furocumarines, salicylates, thiazides and others.

Melanins fulfill important physiological functions by absorbing UV radiation and protecting DNA from the UV radiation related damage. These biopolymers bind some of the chemical compounds used as drugs and thus affect both their metabolism and therapeutic effect. Drugs binding to melanin by electrostatic interactions do not cause toxic side effects while in the case of drugs participating in free-radical type reactions the toxicity increases.

Sulfonamides are the derivatives of 4-aminobenzenosulfonic acid. Anti-bacterial properties of these compounds depend on the presence of an amino group in the para position in relation to the sulfonamide group. Sulfonamides are anti-metabolites of folic acid which is necessary for the synthesis of purine nucleotides. The inhibition of biosynthesis of folic acid is related to structural similarity of sulfonamides and p-aminobenzoic acid (PABA).

The objective of this study was to evaluate the binding of PABA, known as skin photosensitizer, with melanin. The study was conducted in vitro using a model eumelanin synthesized from L-DOPA. Kinetics of drugs-melanin complexes formation as well as binding parameters were determined. Binding of p-aminobenzoic acid to melanin was studied as follows: 5mg of melanin were placed in plastic test-tubes, where drug solutions were added to a final volume of 5 ml. The initial concentration of PABA ranged from 2^.10^-5M to 1.5^.10^-4M. All samples were incubated for 1, 3, 6, 15, 24 and 48 h at room temperature. The suspensions were filtered after incubation. The concentration of unbound drug in each filtrate with respect to the control sample was determined spectrophotometrically, using wavelenght of 265 nm. All spectophotometric measurements were made using the UV-VIS spectrophotometer JASCO model V-530.

It has been demonstrated that p-aminobenzoic acid forms complexes with model melanin in vitro. The amount of PABA bound to melanin increases with the increasing of initial drug concentration and the incubation time. An analysis of PABA binding to melanin by the use of Scatchard plots has shown that only one class of binding sites parcitipates in PABA-melanin complexes formation with the association constant K = 6.54^.10³ M^-1.

The ability of p-aminobenzoic acid to form complexes with melanin in vitro may be one of the reasons of phototoxic effects of this drug in vivo as a result of its accumulation in the skin melanin.

Acnowledgements: This work was financially supported by the Medical University of Silesia

• Legal notice:
  

  Copyright (c) Pielaszek Research, all rights reserved.
  The above materials, including auxiliary resources, are subject to Publisher's copyright and the Author(s) intellectual rights. Without limiting Author(s) rights under respective Copyright Transfer Agreement, no part of the above documents may be reproduced without the express written permission of Pielaszek Research, the Publisher. Express permission from the Author(s) is required to use the above materials for academic purposes, such as lectures or scientific presentations.
  In every case, proper references including Author(s) name(s) and URL of this webpage: https://science24.com/paper/10755 must be provided.