Toxic oil stimulates collagen synthesis acting at a pretranslational level in cultured fat-storing cells

Abstract

Background/Aims: The toxic oil syndrome appeared in Spain in 1981 as a result of ingestion of rapeseed oil denaturated with aniline. Some patients developed sclerodermalike skin lesions and liver cirrhosis. Mechanisms of these fibrotic lesions are not known. The present study was designed to investigate the effect of toxic oils on collagen metabolism. Methods: We measured the relative rate of collagen production, absolute rate of collagen synthesis, production, secretion, and degradation, proline transport, steady-state levels of procollagen α1(I)-messenger RNA (mRNA) in cultured fat-storing cells, and chloramphenicol acetyltransferase activity in transfected cells. Results: Toxic oils increased collagen synthesis, procollagen α1(I)-mRNA levels, and chloramphenicol acetyltransferase activity in cultured fat-storing cells. Effect on collagen production correlated with lipid peroxide content in oils. Cyclo-heximide, α-tocopherol, and methylene blue prevented the increase in procollagen α1(I)-mRNA. Oleylanilide and linoleylanilide, markers for toxic oils, reproduced the stimulatory effects of toxic oils on collagen production and procollagen α1(I)-mRNA. Conclusions: Toxic oils increased collagen synthesis by acting on the promoter of procollagen α1(I) gene, probably through lipid peroxides derived from acylanilides. We suggest that toxic oil may have stimulated procollagen gene expression through the formation of adducts of aldehydes with some transcription factor.