Phytosterol Oxidation Products Are Absorbed in the Intestinal Lymphatics in Rats but Do Not Accelerate Atherosclerosis in Apolipoprotein E–Deficient Mice

Abstract

Phytosterol oxidation products (oxyphytosterols) are formed during the processing and storage of foods. However, it is unknown whether oxyphytosterols affect human health. To address these issues, we prepared beta-sitosterol and campesterol oxides, evaluated their lymphatic absorption in rats, and examined the effect of an oxyphytosterol diet on atherosclerosis in apolipoprotein (apo) E-deficient mice. The lymphatic absorption of cholesterol and 6 oxyphytosterols (7alpha-hydroxy, 7beta-hydroxy, beta-epoxy, alpha-epoxy, dihydroxy, and 7-keto) of beta-sitosterol or campesterol was assessed in thoracic duct-cannulated rats fed an AIN-93G-based diet containing 2.5 g of cholesterol, oxyphytosterols, or intact phytosterols per kg. Lymphatic recoveries (on a mass basis) of oxycampesterols (15.9 +/- 2.8%, n = 10) and oxysitosterols (9.12 +/- 1.77%, n = 10) were higher than for campesterol (5.47 +/- 1.02%, n = 12, P < 0.05) and beta-sitosterol (2.16 +/- 0.37%, n = 12, P < 0.05), but lower than for cholesterol (37.3 +/- 8.3%, n = 6, P < 0.05). Apo E-deficient mice were fed an AIN-93G-based diet containing 0.2 g oxyphytosterols or intact phytosterols per kg for 9 wk. Diet-derived oxyphytosterols accumulated in the serum, liver, and aorta. Furthermore, the oxyphytosterol diet increased oxycholesterol in the serum compared to the phytosterol diet. However, there was no significant difference between the 2 groups in the serum and aortic cholesterol concentration, the lesion area in the aortic root, or 8-iso-prostaglandin F2alpha concentration in the urine. These results indicate that exogenous oxyphytosterols are well-absorbed and accumulate in the body, but do not promote the development of atherosclerosis in apo E-deficient mice.

Oxysterols formation: A review of a multifactorial process

“…As it has been reported, the absorption of campesterol (and its oxides) is higher than that of sitosterol (and its oxides) (12,66 ). Nevertheless, oxysitosterol plasma levels are usually higher than campesterols levels, probably due to in vivo oxidation of sterols (67).…”

“…In this context, there is evidence that SOPs are actually absorbed from the diet (12,13). Given their potentially harmful effects on human health, a deeper study of the factors affecting the formation of dietary SOPs is essential.…”

Oxidation of β-sitosterol and campesterol in sunflower oil upon deep- and pan-frying of French fries

“…1) could have toxic effects on human organisms similar to those of cholesterol oxidation products (COP) (Garcia-Cruset et al 2002). POP were shown to be accumulated in the serum and liver of mice (Tomoyori et al 2004), and to have cytotoxic effects on mammalian cells (Maguire et al 2003). POP were identified in the plasma of human subjects in amounts ranging from 4.80 to 57.2 ng/mL (Grandgirard et al 2004).…”

“…POP were identified in the plasma of human subjects in amounts ranging from 4.80 to 57.2 ng/mL (Grandgirard et al 2004). However, several aspects of the possible toxic effects of POP are still to be elucidated (Tomoyori et al 2004;Lea et al 2004). Maguire et al (2003) reported that β-sitosterol oxides exhibit less severe but similar toxicity patterns to those found for COP.…”

Validation of a gas chromatography–mass spectrometry method for the analysis of sterol oxidation products in serum

“…POPs have been detected to be absorbed in experiments carried out with rats [8][9][10] and they have also been found in human healthy volunteers [11,12]. The toxicological effects of COPs have been well documented because of their wide range of adverse biological effects related to citotoxicity, apoptosis, mutagenesis and carcinogenesis; being specially important the fact that the presence of COPs in human macrophages/foam cells and atherosclerotic plaques has been suggested to induce the development of atherosclerosis [13][14][15][16][17].…”