Histopathological effects of homocysteine thiolactone on epithelial and stromal tissues

To study the effects of homocysteine on epithelial and stromal tissues, the free base of homocysteine thiolactone was synthesized and administered to mice. Intraperitoneal and intramuscular doses of 0.2 to 2.0 mg/g are acutely toxic, causing as much as 90% mortality because of intense tissue necrosis at the injection site, congestion and fibrin thrombi in pulmonary vessels, focal necrosis of liver and kidney, and deposition of lipid within hepatocytes. In survivors of intramuscular injection the area of tissue necrosis is surrounded by fibrosis, calcification, hypertrophy of nerves and ducts, and formation of acanthotic squamous epithelium with hyperkeratosis and focal dysplasia. Topical homocysteine thiolactone on skin is not systemically toxic, but ulceration, fibrosis, acute and chronic inflammation, angiogenesis, acanthosis, hyperkeratosis, and dysplastic squamous epithelium are observed. The findings show that homocysteine thiolactone promotes keratin formation by squamous epithelium, interferes with cellular processes necessary for viability, stimulates epithelial dysplasia and stromal hyperplasia, and produces intravascular fibrin thrombi.