Protective effect of 1,2,4-benzenetriol on LPS-induced NO production by BV2 microglial cells.
Hydroxyhydroquinone or 1,2,4-benzenetriol (BT) detected in the beverages has a structure that coincides with the water-soluble form of a sesame lignan, sesamol. We previously showed that sesame antioxidants had neuroprotective abilities due to their antioxidant properties and/or inducible nitric oxide synthase (iNOS) inhibition. However, studies show that BT can induce DNA damage through the generation of reactive oxygen species (ROS). Therefore, we were interested to investigate the neuroprotective effect of BT in vitro and in vivo. The results showed that instead of enhancing free radical generation, BT dose-dependently (10-100 microM) attenuated nitrite production, iNOS mRNA and protein expression in lipopolysaccharide (LPS)-stimulated murine BV-2 microglia. BT significantly reduced LPS-induced NF-kappaB and p38 MAPK activation. It also significantly reduced the generation of ROS in H2O2-induced BV-2 cells and in H2O2-cellfree conditions. The neuroprotective effect of BT was further demonstrated in the focal cerebral ischemia model of Sprague-Dawley rat. Taken together, the inhibition of LPS-induced nitrite production might be due to the suppression of NF-kappaB, p38 MAPK signal pathway and the ROS scavenging effect. These effects might help to protect neurons from the ischemic injury.
Hou
Rolis Chien-Wei
RC
Jen-Teh Junior College of Medical and Nursing Management, Miaoli, Taiwan.
Chen
Yuh-Shuen
YS
Chen
Chia-Hsin
CH
Chen
Yi-Hsin
YH
Jeng
Kee-Ching G
KC
D000818:Animals; D002545:Brain Ischemia / Q000188:drug therapy / Q000473:pathology; D002460:Cell Line; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology; D006873:Hydroquinones / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008297:Male; D051379:Mice; D017628:Microglia / Q000187:drug effects / Q000378:metabolism; D015394:Molecular Structure; D016328:NF-kappa B / Q000378:metabolism; D018696:Neuroprotective Agents / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D009569:Nitric Oxide / Q000378:metabolism*; D052247:Nitric Oxide Synthase Type II / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D009573:Nitrites / Q000378:metabolism; D016877:Oxidants / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
D006873:Hydroquinones; D008070:Lipopolysaccharides; D016328:NF-kappa B; D018696:Neuroprotective Agents; D009573:Nitrites; D016877:Oxidants; D017382:Reactive Oxygen Species; C013038:hydroxyhydroquinone; D009569:Nitric Oxide; D006861:Hydrogen Peroxide; D052247:Nitric Oxide Synthase Type II; D048051:p38 Mitogen-Activated Protein Kinases