Comparative developmental toxicity of cationic and neutral rhodamines in mice

Publisher Website
Google Scholar
Abstract
Rhodamines 123 and 6G (Rh 123 and Rh 6G) are cationic fluorescent dyes that inhibit oxidative phosphorylation following their selective accumulation within mitochondria. Neutral rhodamines (e.g., Rh 116 and Rh B) do not share these properties. To determine if cationic and neutral rhodamines differ in their effect on mammalian development, pregnant CD‐1 mice were injected i.p. with Rh 123, Rh B, or Rh 116 at doses of 15 mg/kg/day. The rhodamines were given alone or in combination with 500 mg/kg/day 2‐deoxy‐D‐glucose (2‐DOG), an inhibitor of glycolysis, daily on gestation days 7–10 (copulation plug = day 1). Additional pregnant mice were similarly treated with Rh 6G at a dose of 0.5 mg/kg/day. Controls were given saline equimolar to the dose of 2‐DOG. Treatment with Rh 6G, alone or in combination with 2‐DOG, significantly increased the incidences of prenatal mortality (17% and 35%, respectively) when compared with the control incidence (6%). Treatment with Rh 123 or Rh 6G, alone or with 2‐DOG, inhibited fetal growth. Treatment with the neutral rhodamines had little effect on prenatal survival or growth. Exposure to Rh 6G, with or without 2‐DOG, was associated with high incidences of gross malformations (41% and 61%, respectively). Rh 116 or Rh B, with or without 2‐DOG, and Rh 123 alone were not associated with statistically significant teratogenic effects, but results of the latter treatment were suggestive of such an effect (9.1% grossly malformed fetuses vs. 0% for controls). The incidences of skeletal malformations were significantly increased in the test groups given Rh 6G + 2‐DOG, Rh 123 + 2‐DOG, or Rh 6G alone. These results suggest a relationship between the charge on the rhodamine molecule and effects on the conceptus, and these effects may have been mediated at least in part by interference with mitochondrial metabolism.