Modification of retinyl acetate toxicity in rats by coadministration of menhaden oil.

Menhaden oil, which has hypolipidemic and anticarcinogenic activity, reduces the hypertriglyceridemia caused by retinyl acetate. Male Sprague-Dawley rats were dosed daily for 30 days by gavage with either corn oil (CO); menhaden oil (MO); 20, 80, and 250 mg/kg retinyl acetate (ROAc) in CO; or 20, 80, or 250 mg/kg ROAc in MO. Hypertriglyceridemia by ROAc was reduced by coadministration of MO, and serum cholesterol values were reduced to levels similar to those for rats receiving MO alone. Coadministration of MO reduced the ROAc-induced fracture incidence at 80 mg/kg but not at 250 mg/kg. For groups dosed with ROAc and CO or MO, there were no differences in weight-gain depression, elevation of serum alkaline phosphatase, or reduction of food consumption, suggesting that reduced absorption of ROAc was not the basis for the activity of MO. The reduction in retinoid toxicity by MO suggests a need for further study of the toxicity and anticarcinogenicity of retinoid/menhaden oil combinations.