title: 1H NMR-based serum metabolomics reveals erythromycin-induced liver toxicity in albino Wistar rats.
abstract: BACKGROUND
  Erythromycin (ERY) is known to induce hepatic toxicity which mimics other liver diseases. Thus, ERY is often used to produce experimental models of drug-induced liver-toxicity. The serum metabolic profiles can be used to evaluate the liver-toxicity and to further improve the understanding of underlying mechanism.
  
  
  OBJECTIVE
  To establish the serum metabolic patterns of Erythromycin induced hepatotoxicity in albino wistar rats using1H NMR based serum metabolomics.
  
  
  METHODS
  Fourteen male rats were randomly divided into two groups (n= 7 in each group): control and ERY treated. After 28 days of intervention, the metabolic profiles of sera obtained from ERY and control groups were analyzed using high-resolution 1D1H CPMG and diffusion-edited nuclear magnetic resonance (NMR) spectra. The histopathological and SEM examinations were employed to evaluate the liver toxicity in ERY treated group.
  
  
  RESULTS
  The serum metabolic profiles of control and ERY treated rats were compared using multivariate statistical analysis and the metabolic patterns specific to ERY-induced liver toxicity were established. The toxic response of ERY was characterized with: (a) increased serum levels of Glucose, glutamine, dimethylamine, malonate, choline, phosphocholine and phospholipids and (b) decreased levels of isoleucine, leucine, valine, alanine, glutamate, citrate, glycerol, lactate, threonine, circulating lipoproteins, N-acetyl glycoproteins, and poly-unsaturated lipids. These metabolic alterations were found to be associated with (a) decreased TCA cycle activity and enhanced fatty acid oxidation, (b) dysfunction of lipid and amino acid metabolism and (c) oxidative stress.
  
  
  CONCLUSIONS
  Erythromycin is often used to produce experimental models of liver toxicity; therefore, the established NMR-based metabolic patterns will form the basis for future studies aiming to evaluate the efficacy of anti-hepatotoxic agents or the hepatotoxicity of new drug-formulations.
authors.affiliation: Department of Biotechnology, Babasaheb Bhimrao Ambedkar University, Lucknow, Uttar Pradesh, India; Centre of Biomedical Research, Sanjay Gandhi Post Graduate Institute of Medical Sciences Campus, Lucknow, Uttar Pradesh, India.
authors.forename: Atul
authors.initials: A
authors.lastname: Rawat
authors.affiliation: Department of Biotechnology, Babasaheb Bhimrao Ambedkar University, Lucknow, Uttar Pradesh, India; Centre of Biomedical Research, Sanjay Gandhi Post Graduate Institute of Medical Sciences Campus, Lucknow, Uttar Pradesh, India.
authors.forename: Durgesh
authors.initials: D
authors.lastname: Dubey
authors.affiliation: Centre of Biomedical Research, Sanjay Gandhi Post Graduate Institute of Medical Sciences Campus, Lucknow, Uttar Pradesh, India.
authors.forename: Anupam
authors.initials: A
authors.lastname: Guleria
authors.affiliation: Centre of Biomedical Research, Sanjay Gandhi Post Graduate Institute of Medical Sciences Campus, Lucknow, Uttar Pradesh, India.
authors.forename: Umesh
authors.initials: U
authors.lastname: Kumar
authors.affiliation: Department of Pharmaceutical Sciences, Babasaheb Bhimrao Ambedkar University, Lucknow, Uttar Pradesh, India.
authors.forename: Amit K
authors.initials: AK
authors.lastname: Keshari
authors.affiliation: Department of Pharmaceutical Sciences, Babasaheb Bhimrao Ambedkar University, Lucknow, Uttar Pradesh, India.
authors.forename: Swati
authors.initials: S
authors.lastname: Chaturvedi
authors.affiliation: Department of Biotechnology, Babasaheb Bhimrao Ambedkar University, Lucknow, Uttar Pradesh, India.
authors.forename: Anand
authors.initials: A
authors.lastname: Prakash
authors.affiliation: Department of Pharmaceutical Sciences, Babasaheb Bhimrao Ambedkar University, Lucknow, Uttar Pradesh, India.
authors.forename: Sudipta
authors.initials: S
authors.lastname: Saha
authors.affiliation: Centre of Biomedical Research, Sanjay Gandhi Post Graduate Institute of Medical Sciences Campus, Lucknow, Uttar Pradesh, India.
authors.forename: Dinesh
authors.initials: D
authors.lastname: Kumar
keywords: Erythromycin; liver-toxicity; metabolomics; multivariate data analysis; nuclear magnetic resonance; rats