Doxycycline and tissue repair in rats

Steffen Lamparter, Simon H. Slight, Karl Weber

Research output: Contribution to journalArticle

44 Citations (Scopus)

Abstract

Iterations in collagen turnover are integral to tissue repair. Repair gone awry, as a result of excess collagen accumulation or degradation, can contribute to pathologic ventricular remodeling. Pharmacologic interventions that would attenuate either aspect of faulty repair have therefore attracted interest. Tetracyclines, which inhibit both collagen synthesis and degradation, as well as angiogenesis, may hold promise, unrelated to their antimicrobial properties, in this regard. Assessment of their potential in rodent hearts with experimental injury can be problematic, given the often microscopic nature of tissue repair and brief involvement of matrix metalloproteinases (MMPs). We therefore selected a subcutaneous model in which granulation and fibrous tissues form over several weeks in response to croton oil and where fibrous tissue is subsequently resorbed because of high levels of collagenolytic activity. Untreated rats were compared with those given daily oral doxycycline (40 mg/kg). We harvested pouch tissue and exudate weekly for 5 weeks to assess hydroxyproline concentration and MMP activity (gelatin substrate zymography) of pouch wall and mononuclear cell count of pouch exudate. At week 2, neovascularization in pouch wall was measured by means of intravenous infusion of carmine-red dye in gelatin. The resultant "vascular cast" was solubilized and dye content quantitated with the use of spectrophotometry. Serum was assayed weekly for type I collagen carboxyterminal telopeptide (ICTP), a marker of collagen degradation. During weeks 1 and 2 and compared with untreated controls, doxycycline-treated rats had attenuated pouch tissue weight, collagen concentration, MMP2 lytic activity and vascularity, and reduced exudate volume and mononuclear cells. In vitro, doxycycline inhibited tissue gelatinolytic activity in a dose-dependent manner. At weeks 4 and 5, pouches were larger and collagen concentration was higher in doxycycline-treated rats, and serum ICTP levels were reduced at weeks 3 and 4. During the initial phase of pouch development, doxycycline exerts an inhibitory effect on tissue formation, likely mediated through its attenuation of angiogenesis and modulations of collagen turnover. As repair proceeds in subsequent weeks, doxycycline retards collagen degradation and pouch resorption by inhibiting MMPs. Doxycycline offers a multifaceted pharmacologic profile with which to modify various aspects of tissue repair in the rat.

Original languageEnglish (US)
Pages (from-to)295-302
Number of pages8
JournalJournal of Laboratory and Clinical Medicine
Volume139
Issue number5
DOIs
StatePublished - Jan 1 2002

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Doxycycline
Rats
Repair
Collagen
Tissue
Exudates and Transudates
Matrix Metalloproteinases
Degradation
Gelatin
Coloring Agents
Carmine
Croton Oil
Tetracyclines
Ventricular Remodeling
Granulation Tissue
Spectrophotometry
Hydroxyproline
Granulation
Collagen Type I
Cell Size

All Science Journal Classification (ASJC) codes

  • Pathology and Forensic Medicine

Cite this

Doxycycline and tissue repair in rats. / Lamparter, Steffen; Slight, Simon H.; Weber, Karl.

In: Journal of Laboratory and Clinical Medicine, Vol. 139, No. 5, 01.01.2002, p. 295-302.

Research output: Contribution to journalArticle

Lamparter, Steffen ; Slight, Simon H. ; Weber, Karl. / Doxycycline and tissue repair in rats. In: Journal of Laboratory and Clinical Medicine. 2002 ; Vol. 139, No. 5. pp. 295-302.
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