title: Anti-inflammatory properties of doxycycline and minocycline in experimental models: an in vivo and in vitro comparative study.
abstract: OBJECTIVE
  Minocycline (Mino) and doxycycline (Dox) are second generation tetracyclines known to present several other effects, which are independent from their antimicrobial activities. We studied in a comparative way the anti-inflammatory effects of Mino and Dox, on acute models of peripheral inflammation in rodents (formalin test and peritonitis in mice, and carrageenan-induced paw oedema in rats). Immunohistochemical assays for TNF-alpha and iNOS in rat paws of carrageenan-induced oedema were also carried out as well as in vitro assays for myeloperoxidase (MPO) and lactate dehydrogenase (LDH). Furthermore, antioxidant activities were evaluated by the DPPH assay.
  
  
  RESULTS
  In the formalin test although Mino and Dox (1, 5, 10 and 25 mg/kg, i.p.) inhibited the first phase, they acted predominantly on the second phase of the test, where inhibition of the licking time close to 80% were observed. Mino and Dox were very efficacious in reducing the carrageenan-induced paw oedema in rats (10, 25 and 50 mg/kg, i.p.) and carrageenan-induced leucocyte migration (1 and 5 mg/kg, i.p.) to mice peritoneal cavities. Besides, they also significantly inhibited MPO and LDH releases at doses ranging from 0.001 to 1 μg/ml. Thus, in general, the anti-inflammatory activity of Dox was higher as compared to that of Mino, although the radical scavenging activity of Mino was of a magnitude 10 times higher.
  
  
  CONCLUSIONS
  Our data indicate that anti-inflammatory and antioxidant effects, involve the inhibition of iNOS and TNF-alpha, among other properties, and these encourage clinical studies of these compounds for new therapeutic applications, especially those were inflammation plays a role.
authors.affiliation: Faculty of Medicine of Juazeiro de Norte, Av. Tenente Raimundo Rocha s/n, Juazeiro do Norte, 63.040-360, CE, Brazil.
authors.forename: Liz M
authors.initials: LM
authors.lastname: Leite
authors.forename: Antônio Germano G
authors.initials: AG
authors.lastname: Carvalho
authors.forename: Pollyanna L F Tavares
authors.initials: PL
authors.lastname: Ferreira
authors.forename: Igor Xavier
authors.initials: IX
authors.lastname: Pessoa
authors.forename: Danilo O
authors.initials: DO
authors.lastname: Gonçalves
authors.forename: Amanda de Araújo
authors.initials: Ade A
authors.lastname: Lopes
authors.forename: Jean Guilherme dos Santos
authors.initials: JG
authors.lastname: Góes
authors.forename: Victor Costa de Castro
authors.initials: VC
authors.lastname: Alves
authors.forename: Luzia Kalyne A M
authors.initials: LK
authors.lastname: Leal
authors.forename: Gerly Anne
authors.initials: GA
authors.lastname: Brito
authors.forename: Glauce S B
authors.initials: GS
authors.lastname: Viana
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D000975:Antioxidants / Q000737:chemistry; D001713:Biphenyl Compounds / Q000737:chemistry; D002351:Carrageenan / Q000494:pharmacology; D002465:Cell Movement / Q000187:drug effects; D004318:Doxycycline / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D004487:Edema / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control; D005557:Formaldehyde / Q000494:pharmacology; D007249:Inflammation / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D007770:L-Lactate Dehydrogenase / Q000097:blood; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D008911:Minocycline / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D009504:Neutrophils / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D010084:Oxidation-Reduction; D010146:Pain / Q000139:chemically induced / Q000517:prevention & control; D010147:Pain Measurement; D010538:Peritonitis / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control; D009195:Peroxidase / Q000378:metabolism; D010851:Picrates / Q000737:chemistry; D051381:Rats; D017208:Rats, Wistar; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D024502:alpha-Tocopherol / Q000737:chemistry
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D000975:Antioxidants; D001713:Biphenyl Compounds; D010851:Picrates; D014409:Tumor Necrosis Factor-alpha; D005557:Formaldehyde; D002351:Carrageenan; C004931:1,1-diphenyl-2-picrylhydrazyl; D007770:L-Lactate Dehydrogenase; D009195:Peroxidase; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat; D008911:Minocycline; D024502:alpha-Tocopherol; D004318:Doxycycline