Effect of simultaneous use of benzodiazepines and tramadol on human serum metabolome profile

Ziba Akbari,1,* Mohammad arjmand,2 Zeinab madani,3 Ali fathi,4

1. Department of Biochemistry. Pasteur Institute of Iran.
2. Department of Biochemistry. Pasteur Institute of Iran.
3. Dept. of Biochemistry, Payam Noor University of Tehran
4. Dept. of Biochemistry, Payam Noor University of Tehran

Abstract

Introduction

Benzodiazepines are considered as a class of psychoactive drugs. they have sedative, hypnotic, anxiolytic and muscle relaxant properties.tramadol is a highly addictive opioid drug that is routinely prescribed for moderate to severe pain after surgery.tramadol and benzodiazepine are severely abuse among the youngers. however, simultaneous abuse of benzodiazepines and tramadol will be resulted to sever drug toxicity and death. metabolomics is the systematic study of chemical fingerprints resulting from cytotoxic and pathogenic reactions of cells and nuclear magnetic resonance (nmr) spectroscopy is one of the metabolomics tools which is used for drug toxicity.in this project we were going to study the metabolic profile of patients with simultaneous abuse of benzodiazepines and tramadol and the metabolic fingerprint changes were found by the help of h1nmr.

Methods

A total of 20 poisoned patients serum, and 20 normal serums were collected. h1nmr spectroscopy was done according to the cpmg protocol by help of 400 mhz brucker. raw data were analyzed using prometab code and partial least squares-discriminant analysis (pls-da). the altered metabolites and biochemical pathways were identified in the metaboanalyst 4.0 database(www.metaboanalyst.ca).

Results

Our results showed the sharp separation of two groups by pls-da method.the top of 20 compounds chemical shift ranked by variable importance were identified by pls-da. the colored boxes show the relative concentrations of the corresponding metabolite in each group under study and finally the significant altered metabolic pathways in two group were identified by pathway analysis.

Conclusion

In this metabolomics study, the metabolic profile and fingerprint alterations were determined.our results showed that the most altered metabolites and biochemical pathways were in: cystathionine, hydrogen sulfide and cysteine metabolites of sulfur metabolism, cystathionine and taurine metabolites in nitrogen metabolism, and also, methyl-histidine, histidinol, histamine metabolites of histidine metabolism and cystathionine, sarcosine and cysteine metabolites in glycine and serine metabolism. however, more research is need to prove our findings.

Keywords

Benzodiazepines, tramadol, metabolomics, h1nmr.