Effects of fenbufen and other anti-inflammatory drugs on rat liver lysosomes

Fenbufen, biphenylacetic acid and other non-steroidal anti-inflammatory drugs were found to labilize the lysosomal membrane of liver lysosomes in vitro. The extent of labilization was pH dependent. All the non-steroidal drugs labilized to a much greater extent at pH 5.0 than at pH 7.4. The two steroids tested, cholesterol and cortisone, stabilized the lysosomes at both pH 5.0 and 7.4. Oral administration of fenbufen and indomethacin caused no change in lysosomal membrane stability when assayed in vitro. Hydrocortisone showed a small degree of stabilization under these conditions. It is concluded that lysosomal membrane stabilization cannot account for the anti-inflammatory activity of fenbufen, biphenylacetic acid or other non-steroidal anti-inflammatory drugs.