title: The use of nano-quercetin to arrest mitochondrial damage and MMP-9 upregulation during prevention of gastric inflammation induced by ethanol in rat.
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.
authors.affiliation: Drug Development Diagnostics and Biotechnology, CSIR-Indian Institute of Chemical Biology, Jadavpur, Kolkata 700032, India.
authors.forename: Somsuta
authors.initials: S
authors.lastname: Chakraborty
authors.forename: Sami
authors.initials: S
authors.lastname: Stalin
authors.forename: Nirmalendu
authors.initials: N
authors.lastname: Das
authors.forename: Somsubhra Thakur
authors.initials: ST
authors.lastname: Choudhury
authors.forename: Swarupa
authors.initials: S
authors.lastname: Ghosh
authors.forename: Snehasikta
authors.initials: S
authors.lastname: Swarnakar
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology / Q000627:therapeutic use; D000975:Antioxidants / Q000494:pharmacology / Q000627:therapeutic use; D045304:Cytochromes c / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D000431:Ethanol; D005753:Gastric Mucosa / Q000187:drug effects / Q000473:pathology / Q000648:ultrastructure; D005978:Glutathione / Q000378:metabolism; D007249:Inflammation / Q000139:chemically induced / Q000188:drug therapy / Q000517:prevention & control*; D019344:Lactic Acid / Q000737:chemistry; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism*; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008928:Mitochondria / Q000187:drug effects / Q000201:enzymology / Q000473:pathology* / Q000648:ultrastructure; D053758:Nanoparticles / Q000737:chemistry* / Q000648:ultrastructure; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D010316:Particle Size; D009195:Peroxidase / Q000378:metabolism; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D011100:Polyglycolic Acid / Q000737:chemistry; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011794:Quercetin / Q000494:pharmacology* / Q000627:therapeutic use; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism; D013270:Stomach / Q000187:drug effects / Q000201:enzymology / Q000473:pathology* / Q000648:ultrastructure; D013276:Stomach Ulcer / Q000139:chemically induced / Q000188:drug therapy / Q000201:enzymology / Q000517:prevention & control; D015854:Up-Regulation / Q000187:drug effects*
chemical_list: D000893:Anti-Inflammatory Agents; D000975:Antioxidants; D016207:Cytokines; D017382:Reactive Oxygen Species; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D000431:Ethanol; D045304:Cytochromes c; D011794:Quercetin; D009195:Peroxidase; D052247:Nitric Oxide Synthase Type II; D011065:Poly(ADP-ribose) Polymerases; D020780:Matrix Metalloproteinase 9; D005978:Glutathione