Effect Of Diphenoxylate On Rats By Liver Metabonomics

The pethidine derivative diphenoxylate could potentially be used as an alternative to opiates. However, more safety information is needed. In this study, the metabolic changes of liver tissue in rats after administration of diphenoxylate were assessed. Sprague-Dawley rats were randomly divided into four groups. Three groups received diphenoxylate (low, 12 mg/mL; medium, 24 mg/mL; high, 48 mg/mL). The fourth group was a control group. Gas chromatography-mass spectrometry of the liver tissues were collected and analyzed by partial least-squares discriminant analysis, importance in the projection value and combined with t-test p value (p < 0.05) to find differential metabolites. The liver metabonomics of the diphenoxylate groups was altered compared to the control group. Butanoic acid, propanoic acid, glycerol, leucine, glycine, L-aspartic acid, glutamine, xylulose, 9h-purine, gluconic acid, d-mannitol, galactose, and arachidonic acid levels were increased. Myo-inositol level was decreased. The changes were indicative of a disorder in the tricarboxylic acid cycle and abnormalities in the body. The results can provide invaluable information for liver metabonomics after oral administration of diphenoxylate.