Bernal Claudia, Ribeiro Anderson O, Andrade Gislaine P, Perussi Janice R
Instituto de Química de São Carlos, Universidade de São Paulo, São Carlos, SP, Brazil.
Centro Ciências Naturais e Humanas, Universidade Federal do ABC, Santo André, SP, Brazil.
Photodiagnosis Photodyn Ther. 2015 Jun;12(2):176-85. doi: 10.1016/j.pdpdt.2015.04.003. Epub 2015 Apr 22.
Hypericin (HY) is a photoactive aromatic dianthraquinone that is considered a potent photodynamic agent. In this study, hypericin and two other photosensitizers, a hematoporphyrin derivative (Photogem(®); PG) and a chlorin derivative (Photodithazine(®); PZ), were compared in terms of their phototoxicity toward two cell lines, HEp-2 and Vero. The median inhibitory concentration (IC(50)) of each of the photosensitizers was obtained after a 16.2J cm(-2) dose of irradiation at 630 ± 10 nm. The IC(50) values were 0.07 ± 0.01 (HY), 1.0 ± 0.2 (PZ), and 9 ± 1 μgmL(-1) (PG) in HEp-2 cells and 0.3 ± 0.1 (HY), 1.6 ± 0.2 (PZ) and 11 ± 1 μgmL(-1) (PG) in Vero cells, showing that HY is more phototoxic than the others when irradiated at 630 nm. If these results are analyzed, simultaneously, with the first-order constant for BSA tryptophan photooxidation, obtained by fluorescence decay (λ(excitation)=280 nm), which are 11×10(-3) min(-1)±1. 10(-3) min(-1) (HY), 10 × 10(-3) min(-1)±1 × 10(-3) min(-1) (PZ), and 6 × 10(-3)min(-1) ± 1×10(-3)min(-1) (PG), it is possible to infer that the photodynamic efficiency alone is not sufficient to explain the higher HY phototoxicity. The lipophilicity is also an important factor for an efficient target cell accumulation and was assessed for all sensitizers through the octanol-water partition coefficient (log P): 1.20 ± 0.02 (HY), -0.62 ± 0.03 (PZ), and -0.9 ± 0.2 (PG). The higher value for HY correlates well with its observed superior efficiency to promote damage at low concentrations and doses. As HY is used for the long-term treatment of mild depression, it is considered safe for humans. This fact and the present results reinforce the great potential of this photosensitizer to replace porphyrin derivatives, with the advantages that mean it could be used as photosensitizer in clinical photodynamic therapy.
金丝桃素（HY）是一种光活性芳香二蒽醌，被认为是一种有效的光动力剂。在本研究中，比较了金丝桃素与另外两种光敏剂，即血卟啉衍生物（Photogem®；PG）和二氢卟吩衍生物（Photodithazine®；PZ）对两种细胞系（HEp-2和Vero）的光毒性。在630±10nm波长下给予16.2J/cm²的照射剂量后，获得了每种光敏剂的半数抑制浓度（IC₅₀）。在HEp-2细胞中，IC₅₀值分别为0.07±0.01（HY）、1.0±0.2（PZ）和9±1μg/mL（PG）；在Vero细胞中，IC₅₀值分别为0.3±0.1（HY）、1.6±0.2（PZ）和11±1μg/mL（PG），这表明在630nm波长照射时，HY比其他光敏剂具有更高的光毒性。如果将这些结果与通过荧光衰减（激发波长λ=280nm）获得的牛血清白蛋白色氨酸光氧化的一级常数同时进行分析，这些常数分别为11×10⁻³min⁻¹±1×10⁻³min⁻¹（HY）、10×10⁻³min⁻¹±1×10⁻³min⁻¹（PZ）和6×10⁻³min⁻¹±1×10⁻³min⁻¹（PG），则可以推断仅光动力效率不足以解释HY更高的光毒性。亲脂性也是有效靶向细胞积累的一个重要因素，通过正辛醇-水分配系数（log P）对所有光敏剂进行了评估：1.20±0.02（HY）、-0.62±0.03（PZ）和-0.9±0.2（PG）。HY的较高值与其在低浓度和低剂量下观察到的促进损伤的卓越效率密切相关。由于HY用于轻度抑郁症的长期治疗，它被认为对人类是安全的。这一事实和目前的结果强化了这种光敏剂取代卟啉衍生物的巨大潜力，其优势意味着它可作为临床光动力疗法中的光敏剂。
