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Published in: Inflammopharmacology 5/2016

01-10-2016 | Original Article

Redefining the role of peripheral LPS as a neuroinflammatory agent and evaluating the role of hydrogen sulphide through metformin intervention

Authors: Virendra Tiwari, Manjari Singh, Jitendra K. Rawat, Uma Devi, Rajnish K. Yadav, Subhadeep Roy, Swetlana Gautam, Shubhini A. Saraf, Vikas Kumar, Nazam Ansari, Abdulaziz S. Saeedan, Gaurav Kaithwas

Published in: Inflammopharmacology | Issue 5/2016

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Abstract

Objective

The present study was aimed to enumerate the role of metformin-associated H2S release against lipopolysaccharide (LPS) induced neuroinflammation.

Materials and 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.

Result

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.

Conclusion

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.
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Metadata
Title
Redefining the role of peripheral LPS as a neuroinflammatory agent and evaluating the role of hydrogen sulphide through metformin intervention
Authors
Virendra Tiwari
Manjari Singh
Jitendra K. Rawat
Uma Devi
Rajnish K. Yadav
Subhadeep Roy
Swetlana Gautam
Shubhini A. Saraf
Vikas Kumar
Nazam Ansari
Abdulaziz S. Saeedan
Gaurav Kaithwas
Publication date
01-10-2016
Publisher
Springer International Publishing
Published in
Inflammopharmacology / Issue 5/2016
Print ISSN: 0925-4692
Electronic ISSN: 1568-5608
DOI
https://doi.org/10.1007/s10787-016-0274-3

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