Topically applied halofuginone, an inhibitor of collagen type I transcription, reduces peritendinous fibrous adhesions following surgery.
To test in vivo the effect of previously observed inhibition of collagen type I transcription by the plant alkaloid Halofuginone, deep flexor tendons of 12 chickens were severed and sutured, and Halofuginone was applied topically at the site of surgery. Intact tendons, and severed but untreated tendons served as controls. The effect of the treatment was assessed by histological, biochemical, and biomechanical examinations of the operated and intact tendons three weeks after surgery. The results indicated an almost complete absence of fibrous peritendinous adhesions in the histologic sections of the Halofuginone treated tendons. There was a statistically significant decrease in collagen contents of and in both force and energy required to pull out the Halofuginone treated tendons from their sheath, relative to the untreated controls. Halofuginone had no effect on the cellularity of the healing tissue. We conclude that Halofuginone is a potent inhibitor of fibrous peritendinous adhesions with potentially important clinical applications.
Department of Orthopaedic Surgery, Hadassah University Hospital, Jerusalem, Israel.
M
M
Nyska
A
A
Nyska
E
E
Rivlin
S
S
Porat
M
M
Pines
S
S
Shoshan
A
A
Nagler
D000818:Animals; D002645:Chickens; D003094:Collagen / Q000378:metabolism*; D005786:Gene Expression Regulation; D006909:Hydroxyproline / Q000378:metabolism; D007249:Inflammation / Q000188:drug therapy; D010880:Piperidines; D011500:Protein Synthesis Inhibitors / Q000627:therapeutic use*; D011799:Quinazolines / Q000627:therapeutic use*; D052999:Quinazolinones; D018709:Statistics, Nonparametric; D013708:Tendon Injuries / Q000188:drug therapy* / Q000473:pathology / Q000601:surgery; D000267:Tissue Adhesions / Q000473:pathology / Q000517:prevention & control*
D010880:Piperidines; D011500:Protein Synthesis Inhibitors; D011799:Quinazolines; D052999:Quinazolinones; D003094:Collagen; C010176:halofuginone; D006909:Hydroxyproline