title: Evaluation and physiological correlation of plasma proteomic fingerprints for deltamethrin-induced hepatotoxicity in Wistar rats.
abstract: OBJECTIVE
  Uprising reports towards deltamethrin (DLM)-induced toxicity in non-target species including mammals have raised a worldwide concern. Moreover, in the absence of any identified marker, the prediction of DLM elicited early toxic manifestations in non-targets remains elusive.
  
  
  METHODS
  Comprehensive approach of proteome profiling along with conventional toxico-physiological correlation analysis was performed to classify novel protein based markers in the plasma of DLM exposed Wistar rats. Animals were exposed orally to DLM (low dose: 2.56mg/kg b.wt. and high dose: 5.12mg/kg b.wt.) up to seven consecutive days.
  
  
  RESULTS
  The UPLC-MS/MS analysis revealed a dose-dependent dissemination of DLM and its primary metabolite (3-Phenoxy benzoic acid) in rat plasma. Through 2-DE-MS/MS plasma profiling and subsequent verification at the transcriptional level, we found that 6 liver emanated acute phase proteins (Apolipoprotein-AIV, Apolipoprotein E, Haptoglobin, Hemopexin, Vitamin D Binding protein, and Fibrinogen gamma chain) were significantly (p<0.05) modulated in DLM treated groups in a dose-dependent manner. Accordingly, DLM exposure resulted in adverse effects on body growth (body weight & relative organ weight), serum profile, liver function and histology, inflammatory changes (enhanced TNF-ɑ, TGF-β and IL6 level), and oxidative stress. Moreover, these toxic manifestations were suppressed upon N-acetyl cysteine (NAC) supplementation in DLM treated animals. Thus, DLM-induced inflammatory response and subsequent oxidative injury to liver grounds the altered expression of identified acute phase proteins.
  
  
  CONCLUSIONS
  In conclusion, we proposed these six liver emanated plasma proteins as novel candidate markers to assess the early DLM-induced hepatotoxicity in non-target species with a minimal invasive mean.
authors.affiliation: Proteomics Laboratory, Food, Drug & Chemical Toxicology Group, CSIR-Indian Institute of Toxicology Research, 31, Vishvigyan Bhawan, Mahatma Gandhi Marg, Lucknow 226001, (U.P.), India; Department of Bioengineering, Faculty of Engineering, Integral University, Lucknow 226026, (U.P.) India.
authors.forename: Deepika
authors.initials: D
authors.lastname: Arora
authors.affiliation: Department of Bioengineering, Faculty of Engineering, Integral University, Lucknow 226026, (U.P.) India.
authors.forename: Mohammed Haris
authors.initials: MH
authors.lastname: Siddiqui
authors.affiliation: Environmental Carcinogenesis Laboratory, Food, Drug & Chemical Toxicology Group, CSIR-Indian Institute of Toxicology Research, 31, Vishvigyan Bhawan, Mahatma Gandhi Marg, Lucknow 226001, (U.P.), India.
authors.forename: Pradeep Kumar
authors.initials: PK
authors.lastname: Sharma
authors.affiliation: Analytical Toxicology Division, Regulatory Toxicology Group, CSIR-Indian Institute of Toxicology Research, 31, Vishvigyan Bhawan, Mahatma Gandhi Marg, Lucknow 226001, (U.P.), India.
authors.forename: Sheelendra Pratap
authors.initials: SP
authors.lastname: Singh
authors.affiliation: Food Toxicology Laboratory, Food, Drug & Chemical Toxicology Group, CSIR-Indian Institute of Toxicology Research, 31, Vishvigyan Bhawan, Mahatma Gandhi Marg, Lucknow 226001, (U.P.), India.
authors.forename: Anurag
authors.initials: A
authors.lastname: Tripathi
authors.affiliation: Food Toxicology Laboratory, Food, Drug & Chemical Toxicology Group, CSIR-Indian Institute of Toxicology Research, 31, Vishvigyan Bhawan, Mahatma Gandhi Marg, Lucknow 226001, (U.P.), India.
authors.forename: Payal
authors.initials: P
authors.lastname: Mandal
authors.affiliation: Department of Pathology, King George's Medical University, Lucknow 226001, (U.P.), India.
authors.forename: Uma Shankar
authors.initials: US
authors.lastname: Singh
authors.affiliation: Plant Molecular Biology & Genetic Engineering, CSIR-National Botanical Research Institute, Rana Pratap Marg, Lucknow 226001, (U.P.), India.
authors.forename: Pradhyumna Kumar
authors.initials: PK
authors.lastname: Singh
authors.affiliation: Proteomics Laboratory, Food, Drug & Chemical Toxicology Group, CSIR-Indian Institute of Toxicology Research, 31, Vishvigyan Bhawan, Mahatma Gandhi Marg, Lucknow 226001, (U.P.), India; Environmental Carcinogenesis Laboratory, Food, Drug & Chemical Toxicology Group, CSIR-Indian Institute of Toxicology Research, 31, Vishvigyan Bhawan, Mahatma Gandhi Marg, Lucknow 226001, (U.P.), India. Electronic address: yogeshwer_shukla@hotmail.com.
authors.forename: Yogeshwer
authors.initials: Y
authors.lastname: Shukla
mesh_terms: D000818:Animals; D001798:Blood Proteins / Q000378:metabolism*; D008099:Liver / Q000187:drug effects*; D008297:Male; D009570:Nitriles / Q000633:toxicity*; D010575:Pesticides / Q000633:toxicity*; D011722:Pyrethrins / Q000633:toxicity*; D051381:Rats; D017208:Rats, Wistar
chemical_list: D001798:Blood Proteins; D009570:Nitriles; D010575:Pesticides; D011722:Pyrethrins; C017180:decamethrin
keywords: 2-DE; Acute phase proteins; Deltamethrin; Hepatotoxicity; Inflammation; Oxidative stress