Tiwari Virendra, Singh Manjari, Rawat Jitendra K, Devi Uma, Yadav Rajnish K, Roy Subhadeep, Gautam Swetlana, Saraf Shubhini A, Kumar Vikas, Ansari Nazam, Saeedan Abdulaziz S, Kaithwas Gaurav
Department of Pharmaceutical Sciences, School of Biosciences and Biotechnology, Babasaheb Bhimrao Ambedkar University (A Central University), Vidya vihar, Raebareli road, Lucknow, 226025, UP, India.
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.
Inflammopharmacology. 2016 Oct;24(5):253-264. doi: 10.1007/s10787-016-0274-3. Epub 2016 Aug 3.
The present study was aimed to enumerate the role of metformin-associated HS 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 HS, 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 HS, 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.
本研究旨在阐明二甲双胍相关的硫酸乙酰肝素（HS）释放对脂多糖（LPS）诱导的神经炎症的作用。
将五组动物进行如下处理：对照组（生理盐水）、毒性对照组（LPS，125 μg/kg，腹腔注射），以及另外三组分别用6.25、12.5和25 mg/kg二甲双胍与LPS一起处理28天。在第1、2、3、4、23、24、25和26天给予LPS。对动物进行行为学（高架十字迷宫、转棒试验和光电计）、生化指标（血浆和组织中的HS、COX、LOX和NO）、抗氧化指标（TBARS、SOD、过氧化氢酶、蛋白质羰基和GSH）以及肝毒性（SGOT和SGPT）指标的评估。对脑组织进一步进行组织病理学、游离脂肪酸谱和NF-κB表达的评估。
LPS未在脑组织中引发任何显著的行为、生化、抗氧化和组织病理学变化。LPS也未能改变脑组织中的游离脂肪酸谱和NF-κB表达。通过血浆HS、NO、SGOT和SGPT可观察到LPS引发了明确的外周炎症。二甲双胍给药对LPS诱导的外周炎症有显著影响。
腹腔注射LPS没有任何神经炎症作用；然而，会引发外周炎症反应，这可能归因于LPS在血脑屏障中的通透性极低或受限。二甲双胍对LPS引发的外周炎症反应有显著影响。
