Comparative Effects of Phytosterol Oxides and Cholesterol Oxides in Cultured Macrophage-Derived Cell Lines

Abstract

The cytotoxicity of cholesterol and a mixture of beta-sitosterol/campesterol (50%/40%) and their oxides was examined in a cultured-derived macrophage cell line, C57BL/6. Cell numbers, lactate dehydrogenase (LDH) leakage, protein content, lipid uptake, and mitochondria dehydrogenase activity were determined after exposure of cell mononlayers to sterols and sterol oxides at a concentration of 200 microg/mL for up to 120 h. Results indicate that the oxides of cholesterol, beta-sitosterol, and campesterol exhibited similar patterns of toxicity as indicated by LDH leakage, cell viability, and mitochondria dehydrogenase activity. Greatest cell damage was associated with treatments containing 5 alpha,6 alpha-epoxide or cholesterol oxides, followed by beta-sitosterol/campesterol oxides, cholesterol, and beta-sitosterol. The oxides of beta-sitosterol/campesterol caused less LDH leakage and less of an effect on protein content. Results of this study demonstrate that phytosterols contained in vegetable oils, when subjected to frying conditions, do oxidize and may cause cellular damage in an in vitro cell line similar to cholesterol oxides, although less severe.

Different apoptotic mechanisms are involved in the antiproliferative effects of 7β-hydroxysitosterol and 7β-hydroxycholesterol in human colon cancer cells

“…All compounds exhibited similar cytotoxicity as indicated by LDH leakage, cell viability and mitochondria dehydrogenase activity, although oxyphytosterols exerted less severe effects than cholesterol oxides. 23 In the presence of the pancaspase inhibitor, Z-VAD.fmk, apoptotic events were not completely suppressed. 31 Hence, 7b-OHsito may trigger apoptosis through postmitochondrial caspase cascades and DNA fragmentation.…”

“…However, only a few data are available on biological activities of oxyphytosterols. 21,22 It was reported that they cause cellular damage in cultured macrophage-derived cell lines 23 and that hydroxysitosterol induces apoptosis of U937 cells, accompanied by a reduction of cellular glutathione. 24 Furthermore, numerous studies reported atherogenic 25,26 and cytotoxic properties [27][28][29][30] of cholesterol oxides, leading to apoptosis or necrosis in various cell types.…”

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

“…There are only a few reports regarding the cytotoxic effects of POPs, which seem to be less severe [23][24][25]. Some research works attending to find out a proper methodology for the identification and quantification of POPs in vegetable oils, potato chips and French fries [26][27][28], milks [29], enriched spreads [30,31] have been performed.…”

Cytotoxic activity of stigmasteryl esters and products of their thermo-oxidative degradation against drug sensitive and drug resistant human acute lymphoblastic leukemia cells

“…Over the years the cytotoxic effect of phytosterol oxidation products (POP) was investigated and published studies show the toxic activity of POP and cholesterol oxidation products (COP). Some studies present similar effects for both, while others suggest POP have a stronger effect than COP (Adcox et al, 2001;Vejux et al, 2012). Several studies pointed to the potential chemotherapeutic effects of particular phytosterol oxides, because of selective apoptosis induction in cancer cell lines (Samali et al, 1996).…”