Serum metabolic changes in rats of acute paraquat poi- soning treated by pirfenidone

In this study, we developed a gas chromatography-mass spectrometry (GC-MS)-based serum metabolomic analysis method to evaluate the effects of pirfenidone in rats with acute paraquat poisoning. The rats were divided into four groups, acute paraquat poisoning group, low pirfenidone group, high pirfenidone group, and control group. The acute paraquat poisoning group rats were given 20 mg/kg of paraquat by intraperitoneal (ip) administration. In low and high pirfenidone groups, the rats were ip administrated 20 mg/kg of paraquat to induce acute paraquat poisoning, then treated by intragastric (ig) administration of pirfenidone (20 mg/kg and 40 mg/kg, respectively). Compared to acute paraquat poisoning group on the fourth day, pentanedioic acid increased in both low and high pirfenidone group. In addition, d-ribose increased in low pirfenidone group, while ethanedioic acid increased in high pirfenidone group, with à-D-glucopyranoside and glycerol decreased in high pirfenidone group. Compared to acute paraquat poisoning group on the seventh day, no significant differences of metabolite levels were found between acute paraquat poisoning group and pirfenidone groups. The separation between the control group, paraquat poisoning group, and pirfenidone groups in PLS-DA scores were clear. Pathological changes of liver from different groups showed that pirfenidone intervention for paraquat poisonings reduced liver damage. These results indicate that GC-MS based metabolomics analysis method would be useful to elucidate the effect of pirfenidone in rats with acute paraquat poisoning.