Methyl Phenyl Selenide Causes Heme Biosynthesis Impairment and Its Toxicity Is Not Modified by Dimethyl Sulphoxide In Vivo

Abstract

Organoselenium compounds can cause anemia in mice, possibly as a consequence of impairment of the heme biosynthesis pathway. Such compounds can inhibit the sulfhydryl‐containing enzyme δ‐aminolevulinate dehydratase (δ‐ALA‐D), which is involved in the heme biosynthetic pathway, leading to a decrease in the syntheses of hemoglobin, cytochromes and other heme‐proteins. Methyl phenyl selenide (CH₃SePh) has chemopreventive activity against cancer in rodents, raising the possibility of therapeutic use of this compound by humans. Treatment with methyl phenyl selenide (500 µmol/kg/day, 30 days) inhibited the δ‐aminolevulinate dehydratase activity in adult male mice. Furthermore, the exposure to methyl phenyl selenide caused an increase in the liver/body weight ratio and a decrease in the hemoglobin content when compared to the control animals. The vehicle used (DMSO or corn oil) did not affect any of the analyzed parameters or the selenide effects towards these parameters. In summary, results presented here support that δ‐aminolevulinate dehydratase is a potential target to CH₃SePh, leading to an impairment of hemoglobin content, a heme biosynthetic endpoint.

Key Words: :

• Organoselenium compound
• Methyl phenyl selenide
• δ‐aminolevulinate dehydratase
• Hemoglobin content
• Dimethyl Sulphoxide