title: Protective effect of D-002, a mixture of beeswax alcohols, against indomethacin-induced gastric ulcers and mechanism of action.
abstract: D-002, a mixture of higher aliphatic beeswax alcohols, produces gastroprotective and antioxidant effects. To investigate the gastroprotective effect of D-002 against indomethacin-induced ulcers, oxidative variables and myeloperoxidase (MPO) activity in the rat gastric mucosa were examined. Rats were randomized into six groups: a negative vehicle control and five indomethacin (50 mg/kg) treated groups, comprising a positive control, three groups treated orally with D-002 (5, 25 and 100 mg/kg) and one group with omeprazole 20 mg/kg intraperitoneally (ip). The contents of malondialdehyde (MDA), protein carbonyl groups (PCG), hydroxyl radical generation and catalase (CAT), glutathione peroxidase (GSH-PX), superoxide dismutase (SOD) and MPO enzyme activities in the rat gastric mucosa were assessed. Indomethacin increased the content of MDA and PCG, the generation of *OH radical and MPO enzyme activity, while it decreased the CAT, GSH-PX and SOD activities as compared to the negative controls. D-002 (5-100 mg/kg) significantly and dose-dependently reduced indomethacin-induced ulceration to 75 %. Also, D-002 decreased the content of MDA and PCG, the generation of hydroxyl radicals and MPO activity as compared to the positive controls. The highest dose of D-002 (100 mg/kg) increased significantly GSH-PX and SOD activities, while all doses used increased CAT activities. Omeprazole 20 mg/kg, the reference drug, reduced significantly the ulcers (93 %), MDA and PCG, the generation of hydroxyl radicals and MPO activity, and increased the CAT, GSH-PX and SOD activities. D-002 treatment produced gastroprotective effects against indomethacin-induced gastric ulceration, which can be related to the reduction of hydroxyl radical generation, lipid peroxidation, protein oxidation and MPO activity, and to the increase of the antioxidant enzymes activities in the rat gastric mucosa.
authors.affiliation: Centre of Natural Products, National Centre for Scientific Research, Havana, Cuba. yohani.perez@cnic.edu.cu
authors.forename: Yohani
authors.initials: Y
authors.lastname: Pérez
authors.forename: Ambar
authors.initials: A
authors.lastname: Oyárzabal
authors.forename: Rosa
authors.initials: R
authors.lastname: Mas
authors.forename: Vivian
authors.initials: V
authors.lastname: Molina
authors.forename: Sonia
authors.initials: S
authors.lastname: Jiménez
mesh_terms: D000438:Alcohols / Q000737:chemistry / Q000627:therapeutic use*; D000818:Animals; D005979:Glutathione Peroxidase / Q000378:metabolism; D017665:Hydroxyl Radical / Q000378:metabolism; D007213:Indomethacin / Q000633:toxicity*; D015227:Lipid Peroxidation / Q000187:drug effects; D008315:Malondialdehyde / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D013276:Stomach Ulcer / Q000139:chemically induced* / Q000188:drug therapy* / Q000378:metabolism; D013482:Superoxide Dismutase / Q000378:metabolism; D014885:Waxes / Q000737:chemistry*
chemical_list: D000438:Alcohols; D014885:Waxes; C038228:beeswax; D017665:Hydroxyl Radical; D008315:Malondialdehyde; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase; D007213:Indomethacin