Lincomycin-induced cholecystitis and gallstones in guinea pigs

Guinea pigs given lincomycin 60 mg per kg per day showed a striking increase in the renewal of epithelial cells in the gallbladder. This was detectable after only 24 hr of treatment. By 48 hr a precipitate consisting predominantly of calcium and bilirubin had formed in the gallbladder. Gallbladder bile glycoprotein concentrations rose progressively. At 8 days epithelial dysplasia was marked. Treatment was discontinued at 9 days. The guinea pigs that survived beyond 34 days showed that new tubuloalveolar glands had formed focally in the body and fundus of the gallbladder. Multiple calcium-containing stones were present. The failure to culture bacteria from bile, the failure of the bile salt pattern to change, and the progressive nature of the epithelial injury suggested that the changes resulted from a direct toxic effect and were not dependent on the antibiotic activity of this drug. It was concluded that damage to the epithelium of the gallbladder preceded the formation of a precipitate and initiated histological changes which culminated, at the time that the precipitate became organized into stones, in impressive glandular metaplasia.