Department of Paraclinical Sciences, Faculty of Veterinary Science, University of Pretoria, Pretoria, South Africa.
Department of Food Science and Technology, School of Agriculture, University of Venda, Limpopo, South Africa.
PLoS One. 2021 May 4;16(5):e0250408. doi: 10.1371/journal.pone.0250408. eCollection 2021.
Gyps species have been previously shown to be highly sensitive to the toxic effects of diclofenac, when present in their food sources as drug residues following use as a veterinary medicine. Vultures exposed to diclofenac soon become depressed and die with signs of severe visceral gout and renal damage on necropsy. The molecular mechanism behind toxicity and renal excretion of uric acid is still poorly understood. With the clinical pictures suggesting renal uric acid excretion as the target site for toxicity, as a first step the following study was undertaken to determine the uric acid excretory pathways present in the African white-backed vulture (Gyps africanus) (AWB), one of the species susceptible to toxicity. Using transcriptome analysis, immunohistochemistry and functional predictions, we demonstrated that AWB makes use of the organic anion transporter 2 (OAT2) for their uric acid excretion. RT-qPCR analysis subsequently demonstrated relatively similar expression of the OAT2 transporter in the vulture and chicken. Lastly docking analysis, predicted that the non-steroidal drugs induce their toxicity through an allosteric binding.
先前的研究表明，食药残留（如兽医用药后的残留）中的双氯芬酸对吉普赛大兜虫具有高度毒性。暴露于双氯芬酸的秃鹫很快就会出现抑郁，并在尸检时出现严重内脏痛风和肾脏损伤的迹象。尿酸毒性和肾脏排泄的分子机制仍知之甚少。鉴于临床症状表明肾脏尿酸排泄是毒性的靶标，作为第一步，本研究旨在确定易受毒性影响的物种之一——非洲白背秃鹫（Gyps africanus）（AWB）中的尿酸排泄途径。使用转录组分析、免疫组织化学和功能预测，我们证明 AWB 利用有机阴离子转运蛋白 2（OAT2）进行尿酸排泄。随后的 RT-qPCR 分析表明，秃鹫和鸡的 OAT2 转运体表达相对相似。最后，对接分析预测，非甾体类药物通过别构结合诱导其毒性。
