Inhibition of lysyl oxidase by isoniazid and its effect on wound healing.

ABSTRACT

Isoniazid, an antitubercular drug, is known to be a potent inhibitor of monoamine oxidases. Effects of this drug, on lysyl oxidase (also a monoamine oxidase) and other wound healing parameters were studied in albino rats, in presence and absence of pyridoxal phosphate, using a dead space wound model. Tensile strength, collagen and glycosaminoglycan contents as well as lysyl oxidase activity were estimated in the granuloma tissue harvested from 10 day old dead space wounds. Isoniazid inhibited lysyl oxidase activity and a decrease in tensile strength as well as collagen content were observed. The effects were reversed on administration of a stoichiometric amount of pyridoxal phosphate. Hexosamine level was increased and hexuronic acid level decreased in the drug treated animals. Therefore, isoniazid may decrease the mechanical strength of collagen by inhibiting lysyl oxidase, by competiting for its obligatory cofactor pyridoxal phosphate, as well as by interfering in electrostatic interactions between collagen and the ground substance.