Department of Physiology, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, 41390 Gothenburg, Sweden.
Proteomics Core Facility, Sahlgrenska Academy, University of Gothenburg, 41390 Gothenburg, Sweden.
Toxins (Basel). 2018 Aug 17;10(8):333. doi: 10.3390/toxins10080333.
Orellanine is a nephrotoxin found in mushrooms of the Cortinarius family. Accidental intake of this substance may cause renal failure. Orellanine is specific for proximal tubular cells and could, therefore, potentially be used as treatment for metastatic renal cancer, which originates from these cells. However, more information is needed about the distribution and elimination of orellanine from the body to understand its potential use for therapy. In this study, 5 mg/kg orellanine (unlabeled and ³H-labeled) was injected intravenously in rats (Wistar and Sprague Dawley). Distribution was measured (Wistar rats, = 10, = 12) using radioluminography and the highest amount of orellanine was found in the kidney cortex and bladder at all time-points investigated. The pharmacokinetic properties of orellanine was investigated using LC-MS/MS and β-scintillation to measure the amount of orellanine in plasma. Three groups of rats were investigated: control rats with intact kidneys ( = 10) and two groups with bilateral renal artery ligation ( = 7) where animals in one of these groups were treated with peritoneal dialysis ( = 8). Using LC-MS/MS, the half-life of orellanine was found to be 109 ± 6 min in the controls. In the groups with ligated renal arteries, orellanine had a half-life of 756 ± 98 min without and 238 ± 28 min with dialysis. Thus, orellanine was almost exclusively eliminated by glomerular filtration as well as by peritoneal dialysis.
欧芹酸是一种存在于丝盖伞科蘑菇中的肾毒素。误食该物质可能会导致肾衰竭。欧芹酸对近端肾小管细胞具有特异性，因此可能被潜在用作转移性肾细胞癌的治疗药物，因为这种癌症起源于这些细胞。然而，需要更多关于欧芹酸在体内的分布和消除的信息，以了解其作为治疗用途的潜力。在这项研究中，向大鼠（Wistar 和 Sprague Dawley）静脉内注射 5mg/kg 的欧芹酸（未标记和 ³H 标记）。使用放射性闪烁照相术测量分布（Wistar 大鼠，n=10，n=12），在所有研究的时间点，肾脏皮质和膀胱中的欧芹酸含量最高。使用 LC-MS/MS 和β闪烁计数法来测量血浆中欧芹酸的含量，研究了欧芹酸的药代动力学特性。研究了三组大鼠：具有完整肾脏的对照组大鼠（n=10）和双侧肾动脉结扎组（n=7），其中一组动物接受了腹膜透析治疗（n=8）。使用 LC-MS/MS，发现对照组大鼠的欧芹酸半衰期为 109±6 分钟。在肾动脉结扎组中，没有透析的情况下，欧芹酸的半衰期为 756±98 分钟，而有透析的情况下半衰期为 238±28 分钟。因此，欧芹酸几乎完全通过肾小球滤过和腹膜透析来消除。
