1. Academic Validation
  2. The effect of tacrolimus-induced toxicity on metabolic profiling in target tissues of mice

The effect of tacrolimus-induced toxicity on metabolic profiling in target tissues of mice

  • BMC Pharmacol Toxicol. 2022 Nov 28;23(1):87. doi: 10.1186/s40360-022-00626-x.
Dadi Xie # 1 Jinxiu Guo # 2 Ruili Dang # 2 Yanan Li 2 Qingying Si 1 Wenxiu Han 2 Shan Wang 2 Ning Wei 3 Junjun Meng 4 Linlin Wu 5
Affiliations

Affiliations

  • 1 Tengzhou Central People's Hospital, Tengzhou, 277500, China.
  • 2 Translational Pharmaceutical Laboratory, Jining First People's Hospital, Jining, 272000, China.
  • 3 Department of Gastroenterology, Shanting District People's Hospital, Zaozhuang, 277200, China.
  • 4 Translational Pharmaceutical Laboratory, Jining First People's Hospital, Jining, 272000, China. mengjunjunpku@163.com.
  • 5 Tengzhou Central People's Hospital, Tengzhou, 277500, China. linlinliff@163.com.
  • # Contributed equally.
Abstract

Tacrolimus (Tac) is a common immunosuppressant that used in organ transplantation. However, its therapeutic index is narrow, and it is prone to adverse side effects, along with an increased risk of toxicity, namely, cardio-, nephro-, hepato-, and neurotoxicity. Prior metabolomic investigations involving Tac-driven toxicity primarily focused on changes in individual organs. However, extensive research on multiple matrices is uncommon. Hence, in this research, the authors systemically evaluated Tac-mediated toxicity in major organs, namely, serum, brain, heart, liver, lung, kidney, and intestines, using gas chromatography-mass spectrometry (GC-MS). The authors also employed multivariate analyses, including orthogonal projections to the latent structure (OPLS) and t-test, to screen 8 serum metabolites, namely, D-proline, glycerol, D-fructose, D-glucitol, sulfurous acid, 1-monopalmitin (MG (16:0/0:0/0:0)), glycerol monostearate (MG (0:0/18:0/0:0)), and Cholesterol. Metabolic changes within the brain involved alterations in the levels of butanamide, tartronic acid, aminomalonic acid, scyllo-inositol, dihydromorphine, myo-inositol, and 11-octadecenoic acid. Within the heart, the acetone and D-fructose metabolites were altered. In the liver, D-glucitol, L-sorbose, palmitic acid, myo-inositol, and uridine were altered. In the lung, L-lactic acid, L-5-oxoproline, L-threonine, phosphoric acid, phosphorylethanolamine, D-allose, and Cholesterol were altered. Lastly, in the kidney, L-valine and D-glucose were altered. Our findings will provide a systematic evaluation of the metabolic alterations in target organs within a Tac-driven toxicity mouse model.

Keywords

Calcineurin inhibitor; Drug toxicity; Gas chromatography−mass spectrometry; Main tissues; Metabolome.

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