Ballowitz L, Bunjamin A, Hanefeld F, Lietz L, Stüttgen G, Wirjadi D
Pediatr Res. 1979 Dec;13(12):1307-15. doi: 10.1203/00006450-197912000-00001.
Blue and white phototherapy was given to infant (and weanling) homozygous Gunn rats treated with different doses of riboflavin-5-phosphate (ribofl.5'p.) During the first hours after a flavin-injection, the effect of phototherapy with both types of fluorescent lamps was enhanced. With equal radiant power applied, the steepness of serum bilirubin decline depended on the ribofl.5'p. dose injected. After oral or cutaneous application, no similar effect occurred. After a single flavin dose, the serum bilirubin decline lasted for at least 3 hr. Nevertheless, in long-term studies with repeated injections (100 mg/kg every 48 hr), no protective effect beyond that of phototherapy alone could be ascertained on the Purkinje cells in the cerebella of the rats. In the skin of the animals, fluorescence was macroscopically noticeable after ribofl.5'p. injections. When an effective irradiance of about 3.0 mW/cm2 and a high flavin dose (100-200 mg/kg) was administered, histologic investigations of the skin in the abdominal and back region revealed a reversible inflammatory reaction with edema and morphologic changes in the epidermal cells that culminated 12-24 hr after the injection. After a further increase of the effective irradiance, tremendous vesicles on paws, ears, and tails were observed in most of the animals 24-72 hr after the flavin injections. The content of the blisters was primarily serous, later on, often hemorrhagic. Finally, necrosis developed. Acute toxicity of ribofl.5'p. differed markedly when the infant rats (homozygous jaundiced as well as heterozygous nonjaundiced) were kept in the dark or under intense blue phototherapy. Much higher doses were tolerated in the dark. Moreover, it could be demonstrated that ribofl.5'p. does not influence serum bilirubin of jaundiced Gunn rats kept in complete darkness. That suggests that the drug itself does not compete for albumin binding sites. But certain riboflavin ampules (Beflavin) contain stabilizers that considerably displace bilirubin from albumin bonds. Riboflavin disturbs direct photometric bilirubin measurements, but not the diazo reaction. When bilirubin is to be measured in sera containing riboflavin, lights must be extremely dim. Photodegradation in vitro is highly accelerated by the sensitizer.
对用不同剂量的磷酸核黄素（ribofl.5'p.）治疗的纯合子冈恩幼鼠（及断奶幼鼠）进行蓝白光照疗法。在注射黄素后的最初几个小时内，两种荧光灯的光照疗法效果均增强。在施加相同辐射功率的情况下，血清胆红素下降的陡度取决于注射的ribofl.5'p.剂量。经口服或皮肤给药后，未出现类似效果。单次给予黄素剂量后，血清胆红素下降持续至少3小时。然而，在重复注射（每48小时100mg/kg）的长期研究中，未发现对大鼠小脑浦肯野细胞有超出单独光照疗法的保护作用。在动物皮肤中，注射ribofl.5'p.后在宏观上可观察到荧光。当给予约3.0mW/cm²的有效辐照度和高剂量的黄素（100 - 200mg/kg）时，对腹部和背部皮肤进行组织学检查发现，在注射后12 - 24小时出现了伴有水肿的可逆性炎症反应以及表皮细胞的形态学变化。在进一步提高有效辐照度后，在大多数动物中，黄素注射后24 - 72小时在爪子、耳朵和尾巴上观察到巨大水疱。水疱内容物起初主要是浆液性的，后来常常是血性的。最后发展为坏死。当将纯合子黄疸幼鼠和杂合子非黄疸幼鼠置于黑暗中或强烈的蓝光照射疗法下时，磷酸核黄素的急性毒性有明显差异。在黑暗中能耐受更高的剂量。此外，可以证明，磷酸核黄素对完全处于黑暗中的黄疸冈恩大鼠的血清胆红素没有影响。这表明该药物本身不竞争白蛋白结合位点。但是某些核黄素安瓿（贝弗拉文）含有稳定剂，这些稳定剂会使胆红素从白蛋白结合中大量置换出来。核黄素会干扰直接光度法测定胆红素，但不影响重氮反应。当要在含有核黄素的血清中测定胆红素时，光线必须极其昏暗。敏化剂会极大地加速体外光降解。
