Urinary metabolic profiling of rats with articular cartilage damage induced by T-2 toxin / 中华地方病学杂志

ABSTRACT

Objective To search for the metabolites that associated with articular cartilage damage in the urine of rat model with articular cartilage destruction induced by T-2 toxin.Methods Thirty healthy male Wistar rats aged 4-5 weeks were numbered by weight,randomly divided into two groups (n =15 per group),namely the control group and the model group.The rats in the control group were fed with standard rat diets,and those in the model group were given diets contaminated by T-2-toxin (300 μg/kg).Throughout the experiment,all animals were given free access to distilled water and diets.After continuous treatment for 3 months,all the rats were sacrificed.The changes of articular cartilage in rat knee joints were observed by histopathological method,the metabolic profile of rats' urine was determined by ultra performance liquid chromatography/quadrupole time of flight-mass spectrometry (UPLC/QTOF-MS) technique.Combined with multivariate statistical analysis,database searching was applied to explore and confirm the different metabolites associated with cartilage damage.Results Light microscope showed that rats' articular chondrocytes in the control group presented cells in neat rows and eumorphism,rats' articular chondrocytes in the model group presented extensive areas of chondrocyte degeneration,necrosis and loss.In rats' urine metabolic profiles,5 different metabolites associated with cartilage destruction were detected,such as 4-hydroxynonenal (HNE),trans-4,5-epoxy-2(E)-decenal (EDE),5-methyldeoxycytidine,and 5-L-glutamyl-glycine and prolyl-valine.Compared with the control group (mass spectrum peak area65820 ± 5200,22080 ± 3538,4292 ± 3520,3277 ± 2025,1104 ± 990),all of them increased in the model group (mass speetrum peak area90240 ± 18863,25610 ± 5071,9702 ± 6562,6029 ± 3905,4144 ± 5322,t =-3.903,-2.209,-2.814,-2.424,-2.174,all P ＜ 0.05).Conclusions The articular cartilage destruction induced by T-2 toxin could cause the changes of related metabolites in the urine;the 5 kinds of changed metabolites in urine are related to articular cartilage destruction.