The use of nano-quercetin to arrest mitochondrial damage and MMP-9 upregulation during prevention of gastric inflammation induced by ethanol in rat

• Published in: Biomaterials 2012-04, Vol.33 (10), p.2991-3001
• Main Authors: Chakraborty, Somsuta, Stalin, Sami, Das, Nirmalendu, Thakur Choudhury, Somsubhra, Ghosh, Swarupa, Swarnakar, Snehasikta
• Format: Article
• Language: English
• Subjects: Advanced Basic Science; Animals; Anti-Inflammatory Agents - pharmacology; Anti-Inflammatory Agents - therapeutic use; Antioxidants - pharmacology; Antioxidants - therapeutic use; Atomic force microscopy; Cytochromes c - metabolism; Cytokines - metabolism; Dentistry; Ethanol; Gastric Mucosa - drug effects; Gastric Mucosa - pathology; Gastric Mucosa - ultrastructure; Gastric ulcer; Glutathione - metabolism; Inflammation - chemically induced; Inflammation - drug therapy; Inflammation - prevention & control; Lactic Acid - chemistry; Male; Matrix Metalloproteinase 9 - metabolism; Matrix metalloproteinase-9; Membrane Potential, Mitochondrial - drug effects; Mitochondria - drug effects; Mitochondria - enzymology; Mitochondria - pathology; Mitochondria - ultrastructure; Nanocapsulated quercetin; Nanoparticles - chemistry; Nanoparticles - ultrastructure; Nitric oxide synthase; Nitric Oxide Synthase Type II - metabolism; Oxidative stress; Particle Size; Peroxidase - metabolism; Poly(ADP-ribose) Polymerases - metabolism; Polyglycolic Acid - chemistry; Quercetin - pharmacology; Quercetin - therapeutic use; Rats; Rats, Sprague-Dawley; Reactive Oxygen Species - metabolism; Stomach - drug effects; Stomach - enzymology; Stomach - pathology; Stomach - ultrastructure; Stomach Ulcer - chemically induced; Stomach Ulcer - drug therapy; Stomach Ulcer - enzymology; Stomach Ulcer - prevention & control; Up-Regulation - drug effects
• ISSN: 0142-9612; 1878-5905
• DOI: 10.1016/j.biomaterials.2011.12.037

Abstract Gastric ulcer is a multifaceted process that involves reactive oxygen species (ROS) generation, extracellular matrix degradation and mitochondrial damage. Mitochondria play a crucial role for homeostasis of ROS and cell survival. In our study, we investigated the efficacy and mechanism of polymeric nanocapsuled quercetin (NQC) over the free quercetin (QC) molecule in prevention of ethanol-induced gastric ulcer in rat. NQC possessed significantly higher efficacy (∼20 fold) than free QC while preventing gastric ulcers. Our data show that prior administration of NQC and/or QC significantly blocked synthesis and secretion of matrix metalloproteinase (MMP)-9 as well as infiltration of inflammatory cells and oxidative damage in rat gastric tissues. As compared to free QC, NQC protected much better the mitochondrial integrity and size along with mitochondrial functions by controlling succinate dehydrogenase and NADH oxidase in rat gastric tissues. In addition, both free QC and NQC down regulated PARP-1 as well as apoptosis during protection against ethanol-induced gastric ulcer. Herein, the effect of NQC was greater than QC on expression of enzymes like cyclooxygenase and nitric oxidase synthase (NOS)-2. We conclude that NQC with greater bioavailability offers significantly higher potency in downregulating MMP-9 and NOS-2 as well as oxidative stress in blocking ethanol-induced gastric ulcer.