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

Autor: Uma Devi, Vikas Kumar, Subhadeep Roy, Nazam Ansari, Gaurav Kaithwas, Jitendra K. Rawat, Manjari Singh, Swetlana Gautam, Rajnish Kumar Yadav, Virendra Tiwari, Abdulaziz S. Saeedan, Shubhini A. Saraf
Rok vydání: 2016
Předmět:
Zdroj: Inflammopharmacology. 24:253-264
ISSN: 1568-5608
0925-4692
DOI: 10.1007/s10787-016-0274-3
Popis: The present study was aimed to enumerate the role of metformin-associated H2S release against lipopolysaccharide (LPS) induced neuroinflammation. 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. 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. 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.
Databáze: OpenAIRE