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Modification of retinyl acetate toxicity in rats by coadministration of menhaden oil
C Lindamood1, L Mac Thigpen, H D Giles
1Kettering-Meyer Laboratory, Southern Research Institute, Birmingham, Alabama 3255-5305.
Abstract:
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.
Insights
Menhaden oil (MO) reduces high triglycerides and cholesterol caused by retinyl acetate (ROAc) in rats. MO also lessened ROAc-induced fractures, indicating potential for combined retinoid and fish oil therapies.
Area of Science:
- Biochemistry
- Pharmacology
- Toxicology
Background:
- Menhaden oil (MO) exhibits hypolipidemic and anticarcinogenic properties.
- Retinyl acetate (ROAc) can induce hypertriglyceridemia and other toxic effects.
Purpose of the Study:
- To investigate the effects of menhaden oil (MO) on retinyl acetate (ROAc)-induced hypertriglyceridemia and toxicity in rats.
- To evaluate the potential of MO as a counteragent to ROAc-induced adverse effects.
Main Methods:
- Male Sprague-Dawley rats were administered daily doses of corn oil (control), MO, ROAc in corn oil, or ROAc in MO for 30 days.
- Serum triglyceride and cholesterol levels, fracture incidence, body weight, food consumption, and serum alkaline phosphatase were monitored.
Main Results:
- Coadministration of MO significantly reduced ROAc-induced hypertriglyceridemia and lowered serum cholesterol.
- MO reduced ROAc-induced fracture incidence at a dose of 80 mg/kg but not 250 mg/kg.
- No significant differences were observed in weight gain, food consumption, or alkaline phosphatase levels, suggesting MO's activity is not due to reduced ROAc absorption.
Conclusions:
- Menhaden oil effectively mitigates key toxicities associated with retinyl acetate administration in rats.
- These findings suggest a potential therapeutic benefit of combining retinoids with menhaden oil, warranting further investigation into their combined toxicity and anticarcinogenic potential.

