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.

Fluoride is widely present in the environment. Excessive fluoride exposure leads to fluorosis, which has become a global public health problem and will cause damage to various organs and tissues. Only a few studies focus on serum metabolomics, and there is still a lack of systematic metabolomics associated with fluorosis within the main organs. Therefore, in the current study, a non-targeted metabolomics method using gas chromatography-mass spectrometry (GC-MS) was used to research the effects of fluoride exposure on metabolites in different organs, to uncover potential biomarkers and study whether the affected metabolic pathways are related to the mechanism of fluorosis. Male Sprague-Dawley rats were randomly divided into two groups: a control group and a fluoride exposure group. GC-MS technology was used to identify metabolites. Multivariate statistical analysis identified 16, 24, 20, 20, 24, 13, 7, and 13 differential metabolites in the serum, liver, kidney, heart, hippocampus, cortex, kidney fat, and brown fat, respectively, in the two groups of rats. Fifteen metabolic pathways were affected, involving toxic mechanisms such as oxidative stress, mitochondrial damage, inflammation, and fatty acid, amino acid and energy metabolism disorders. This study provides a new perspective on the understanding of the mechanism of toxicity associated with sodium fluoride, contributing to the prevention and treatment of fluorosis.