Topical beta-aminopropionitrile and biochemistry of granuloma tissue

The changes of connective tissue in granuloma development were studied up to 20 days following subcutaneous implantation of polyvinyl alcohol (PVA) sponges in rats. The total protein and collagen content were found to increase from the 4th to 12th days of implantation while the content of DNA continuously decreased with the age of the granuloma. Administration of beta-aminopropionitrile (beta APN) fumarate on the intact skin overlying the implanted PVA sponge in the presence and absence of dimethyl sulfoxide (DMSO) during the growth phase of granuloma development (4th through 12th days after implantation) was accompanied by significant inhibition of collagen polymerization. This was documented by a significant increase of collagen extractable into 1 N NaCl, by a significantly reduced content of aldehydes in collagens extractable into neutral salt solution, and by a significant increase of alpha subunits and alpha/beta ratio. Topical beta APN administration had no effect on the content of DNA, noncollagenous proteins, or total hydroxyproline. We conclude that topically administered beta APN fumarate onto the intact skin penetrates the stratum corneum and effectively inhibits collagen crosslinking in the underlying granuloma tissue. The extent of the effectiveness was found to be significantly greater in the presence of DMSO.