Tryptophan Pathway-Targeted Metabolomics Study on the Mechanism and Intervention of Cisplatin-Induced Acute Kidney Injury in Rats was written by Tan, Bei;Chen, Jie;Qin, Siyuan;Liao, Chuyao;Zhang, Ying;Wang, Di;Li, Siqi;Zhang, Zunjian;Zhang, Pei;Xu, Fengguo. And the article was included in Chemical Research in Toxicology in 2021.Application of 533-45-9 This article mentions the following:
Cisplatin is a chemotherapeutic agent widely employed in the treatment of various solid tumors. However, its use is often restricted by acute kidney injury (AKI) which is the dose-limiting adverse effect of cisplatin. While numerous studies aiming to alleviate the AKI have been conducted, there are no effective remedies in clin. practice. In this paper, a targeted metabolomics study was performed to reveal the potential relationship between tryptophan metabolism and cisplatin-induced AKI. A chem. derivatization integrated liquid chromatog. coupled tandem mass spectrometry (LC-MS/MS) approach was utilized to quantify 29 metabolites in the tryptophan pathway in rat kidney medulla and cortex after cisplatin administration. Results showed that tryptophan metabolism was remarkably disturbed both in the medulla and cortex after cisplatin administration. We also found that the tryptophan pathway in the medulla was more sensitive to cisplatin exposure compared with the cortex. Among these metabolites, indoxyl sulfate was focused for further study because it accumulated most significantly in the kidney cortex and medulla in a dose-dependent manner. A function verification study proved that chlormethiazole, a widely used CYP2E1 inhibitor, could reduce the production of indoxyl sulfate in the liver and attenuate cisplatin-induced AKI in rats. In conclusion, our study depicted the tryptophan pathway in cisplatin-induced AKI for the first time and demonstrated tryptophan metabolism is closely associated with the renal toxicity caused by cisplatin, which can be of great use for the discovery of renal toxicity attenuating remedies. In the experiment, the researchers used many compounds, for example, 5-(2-Chloroethyl)-4-methylthiazole (cas: 533-45-9Application of 533-45-9).
5-(2-Chloroethyl)-4-methylthiazole (cas: 533-45-9) belongs to thiazole derivatives. Thiazole is a five-membered, unsaturated, planar, π-excessive heteroaromatic containing one sulfur atom and one pyridine-type nitrogen atom at position 3 of the cyclic ring system. Thiazole sulfonation occurs only under forcing conditions: the action of oleum at 250 °C for 3 hours in the presence of mercury(II) sulfate leads to 65% formation of 5-thiazole sulfonic acid.Application of 533-45-9
Referemce:
Thiazole | C3H3NS – PubChem,
Thiazole | chemical compound | Britannica