Morphologic and biochemical effects of doxycycline on collagen structure in experimental lathyrism

Abstract

Background and Design: Lathyrism is characterized by defective collagen synthesis due to inhibition of lysyl oxidase, which is essential for interfibrillar cross-linking. Lathyritic agent b-aminoproprionitrile (?-APN) accepted as a suitable agent for the study of connective tissue metabolism. Tetracyclines are known to inhibit the matrix metalloproteinases such as collagenase and gelatinase. Doxycyclin is the most potent matrix metalloproteinase inhibitor among antimicrobial tetracyclines. Our purpose was to investigate the role of doxycycline on collagen structure in experimentally induced lathyrism by electron microscopically and biochemically. Materials and Methods: Thirty Wistar rats weighting between 250-300 gm were used in this study. Twenty rats were used as test (group 2 and 3) and 10 rats were used as control group (group 1). Experimental lathyrism was created with daily subcutaneous injection of lathyritic agent ?-APN for 40 days in 20 rats (group 2 and 3). At day 40, skin biopsies were taken from 10 rats of the test group (group 2) to evaluate the effect of ?-APN on dermal collagen. After 40 days, in the third group (10 rats) doxycycline 21 mg daily was administered orally for 15 days. In the first group (10 rats) no medication was performed after 40 days. At day 55, skin biopsies were taken from the first and third group, Serum IL-6 levels were measured by ELISA. Results: We did not observe remarkable improvement in the third group both electron microscopically and biochemically. Conclusion: Administration of doxycycline by oral route did not improve the structure of collagen both morphologically and biochemically, in experimentally induced lathyrism.