Review of Animal Models in Carotenoid Research

Abstract

Foods containing provitamin A carotenoids are the primary source of vitamin A in many countries, despite the poor bioavailability of carotenoids. In addition, epidemiologic studies suggest that dietary intake of carotenoids influences the risk for certain types of cancer, cardiovascular disease and other chronic diseases. Although it would be ideal to use humans directly to answer critical questions regarding carotenoid absorption, metabolism and effects on disease progression, appropriate animal models offer many advantages. This paper will review recent progress in the development of animal models with which to study this class of nutrients. Each potential model has strengths and weaknesses. Like humans, gerbils, ferrets and preruminant calves all absorb beta-carotene (betaC) intact, but only gerbils and calves convert betaC to vitamin A with efficiency similar to that of humans. Mice and rats efficiently convert betaC to vitamin A but absorb carotenoids intact only when they are provided in the diet at supraphysiologic levels. Mice, rats and ferrets can be used to study cancer, whereas primates and gerbils are probably more appropriate for studies on biomarkers of heart disease. No one animal model completely mimics human absorption and metabolism of carotenoids; thus the best model must be chosen with consideration of the specific application being studied, characteristics of the model, and the available funding and facilities.

Nutritionally Enhanced Staple Food Crops

“…The most frequently used animals for nutrition research are chicken, mouse, rat, gerbil, preruminant calf, ferret, nonhuman primate, pig or piglets, hamster, and dog (Lee et al 1999), which have been valuable in advancing our knowledge of nutrition, with many exhibiting welldocumented differences versus humans in how they use, metabolize, and excrete nutrients (Lee et al 1999;Baker 2008). However, because of species differences it is important to choose the right animal model for prediction of what might happen in humans.…”

“…An ideal model for carotenoids research should be the one that (1) absorb a variety of carotenoids intact at the physiologic levels in the same way as with humans, (2) have carotenoids distribution in tissues similar to that of humans, and (3) represent an appropriate model for the disease state of interest as many diseases in humans have been diagnosed due to vitamin deficiency. Like humans, gerbil, ferrets, and preruminant calves all absorb b-carotene intact, but only gerbils and calves convert b-carotene to vitamin A with efficiency similar to that of humans (Lee et al 1998(Lee et al , 1999Howe and Tanumihardjo 2006). The gerbils are small, easily maintained in large numbers, and readily available.…”

“…The gerbils are small, easily maintained in large numbers, and readily available. They are also an established model for cholesterol and lipid metabolism because their serum lipid profile responds to dietary changes similarly to humans (Lee et al 1999).…”

Vertebrate and invertebrate carotenoid-binding proteins

“…Thus, cellular carotenoid and retinoid binding proteins are expected to be found in abundant amounts in animal liver tissue. Several animal models have been studied in the past to identify carotenoid metabolism and role of hepatic binding proteins [82][83]. Ferrets are known to absorb dietary beta-carotene intact and are considered an ideal animal model for studies on carotenoid absorption and bioavailability.…”

Low doses of β‐carotene and lutein inhibit AOM‐induced rat colonic ACF formation but high doses augment ACF incidence

“…14,15 Supplementing diets with ␤-carotene failed to reduce colon cancers and adenomas, and also other cancers in well-designed long-term human intervention studies. 16 Animal model studies of various cancers examining the effects of dietary ␤-carotene have led to conflicting results (reviewed in 17,18). Protective effects of ␤-carotene were observed against colon cancer, 19 -22 with a significant potential to inhibit ACF, the putative preneoplastic lesions in the colon.…”