title: Redefining the role of peripheral LPS as a neuroinflammatory agent and evaluating the role of hydrogen sulphide through metformin intervention.
abstract: OBJECTIVE
  The present study was aimed to enumerate the role of metformin-associated H2S release against lipopolysaccharide (LPS) induced neuroinflammation.
  
  
  METHODS
  Five groups of animals were subjected to treatment as control (normal saline), toxic control (LPS, 125 µg/kg, i.p.), and three separate groups treated with 6.25, 12.5, and 25 mg/kg of metformin along with LPS for a period of 28 days. LPS was administered on 1st, 2nd, 3rd, 4th, 23rd, 24th, 25th and 26th day. The animals were evaluated for behavioral (elevated plus maze, rotarod and actophotometer); biochemical (plasma and tissue H2S, COX, LOX and NO), antioxidant (TBARS, SOD, catalase, protein carbonyl and GSH) and liver toxicity (SGOT and SGPT) markers. The brain tissues were further evaluated histopathologically, free fatty acid profile and NF-κB expression.
  
  
  RESULTS
  The LPS could not hasten any significant behavioral, biochemical, antioxidant and histopathological changes in the brain tissue. LPS also failed to modify the free fatty acid profile and NF-κB expression in the brain tissue. The LPS demarcated a well-defined peripheral inflammation as perceived through the plasma H2S, NO, SGOT and SGPT. Metformin administration demonstrated a marked effect on the peripheral inflammation induced by LPS.
  
  
  CONCLUSIONS
  The LPS (i.p.) administration is devoid of any neuroinflammatory effects; however, precipitates peripheral inflammatory reactions and the same can could be attributed to the fact that LPS is devoid of/confined by very minimal permeability across the blood brain barrier. Metformin demonstrated a significant effect on peripheral inflammatory reactions precipitated through LPS.
authors.affiliation: Department of Pharmaceutical Sciences, School of Biosciences and Biotechnology, Babasaheb Bhimrao Ambedkar University (A Central University), Vidya vihar, Raebareli road, Lucknow, 226025, UP, India.
authors.forename: Virendra
authors.initials: V
authors.lastname: Tiwari
authors.affiliation: Department of Pharmaceutical Sciences, School of Biosciences and Biotechnology, Babasaheb Bhimrao Ambedkar University (A Central University), Vidya vihar, Raebareli road, Lucknow, 226025, UP, India.
authors.forename: Manjari
authors.initials: M
authors.lastname: Singh
authors.affiliation: Department of Pharmaceutical Sciences, School of Biosciences and Biotechnology, Babasaheb Bhimrao Ambedkar University (A Central University), Vidya vihar, Raebareli road, Lucknow, 226025, UP, India.
authors.forename: Jitendra K
authors.initials: JK
authors.lastname: Rawat
authors.affiliation: Department of Pharmaceutical Sciences, Faculty of Health Medical Sciences Indigenous and Alternative Medicine, SHIATS-Deemed to be University, Formerly Allahabad Agricultural Institute, Naini, Allahabad, UP, India.
authors.forename: Uma
authors.initials: U
authors.lastname: Devi
authors.affiliation: Department of Pharmaceutical Sciences, School of Biosciences and Biotechnology, Babasaheb Bhimrao Ambedkar University (A Central University), Vidya vihar, Raebareli road, Lucknow, 226025, UP, India.
authors.forename: Rajnish K
authors.initials: RK
authors.lastname: Yadav
authors.affiliation: Department of Pharmaceutical Sciences, School of Biosciences and Biotechnology, Babasaheb Bhimrao Ambedkar University (A Central University), Vidya vihar, Raebareli road, Lucknow, 226025, UP, India.
authors.forename: Subhadeep
authors.initials: S
authors.lastname: Roy
authors.affiliation: Department of Pharmaceutical Sciences, School of Biosciences and Biotechnology, Babasaheb Bhimrao Ambedkar University (A Central University), Vidya vihar, Raebareli road, Lucknow, 226025, UP, India.
authors.forename: Swetlana
authors.initials: S
authors.lastname: Gautam
authors.affiliation: Department of Pharmaceutical Sciences, School of Biosciences and Biotechnology, Babasaheb Bhimrao Ambedkar University (A Central University), Vidya vihar, Raebareli road, Lucknow, 226025, UP, India.
authors.forename: Shubhini A
authors.initials: SA
authors.lastname: Saraf
authors.affiliation: Department of Pharmaceutical Sciences, Faculty of Health Medical Sciences Indigenous and Alternative Medicine, SHIATS-Deemed to be University, Formerly Allahabad Agricultural Institute, Naini, Allahabad, UP, India.
authors.forename: Vikas
authors.initials: V
authors.lastname: Kumar
authors.affiliation: Department of Pharmacology, College of Pharmacy, Prince Sattam Bin Abdulaziz University, Al-Kharj, Saudi Arabia.
authors.forename: Nazam
authors.initials: N
authors.lastname: Ansari
authors.affiliation: Department of Pharmacology, College of Pharmacy, Prince Sattam Bin Abdulaziz University, Al-Kharj, Saudi Arabia.
authors.forename: Abdulaziz S
authors.initials: AS
authors.lastname: Saeedan
authors.affiliation: Department of Pharmaceutical Sciences, School of Biosciences and Biotechnology, Babasaheb Bhimrao Ambedkar University (A Central University), Vidya vihar, Raebareli road, Lucknow, 226025, UP, India. gauravpharm@hotmail.com.
authors.forename: Gaurav
authors.initials: G
authors.lastname: Kaithwas
mesh_terms: D000818:Animals; D006862:Hydrogen Sulfide / Q000378:metabolism*; D007004:Hypoglycemic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D007249:Inflammation / Q000139:chemically induced / Q000188:drug therapy / Q000378:metabolism; D018836:Inflammation Mediators / Q000037:antagonists & inhibitors / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000633:toxicity*; D008297:Male; D018782:Maze Learning / Q000187:drug effects / Q000502:physiology; D008687:Metformin / Q000494:pharmacology / Q000627:therapeutic use*; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar
chemical_list: D007004:Hypoglycemic Agents; D018836:Inflammation Mediators; D008070:Lipopolysaccharides; D008687:Metformin; D006862:Hydrogen Sulfide
keywords: Hydrogen sulphide; Lipopolysaccharide; Metformin; NF-κB; Neuroinflammation