Serum 27-hydroxycholesterol in patients with primary biliary cirrhosis suggests alteration of cholesterol catabolism to bile acids via the acidic pathway

Abstract

Reduced cholesterol synthesis has been reported in patients with primary biliary cirrhosis but no data are available on changes in cholesterol catabolism induced by the disease. Serum levels of 7 ␣ -hydroxycholesterol and 27hydroxycholesterol have been measured in 25 patients (either normocholesterolemic or hypercholesterolemic) with primary biliary cirrhosis and in control subjects. To evaluate cholesterol synthesis, serum levels of lathosterol were measured, and campesterol and sitosterol were considered to reflect intestinal absorption and biliary elimination of sterols. In normocholesterolemic patients with primary biliary cirrhosis, lathosterol was significantly lower than in normocholesterolemic controls ( P Ͻ 0.05) whereas no difference was found between hypercholesterolemic patients and hypercholesterolemic controls. Serum concentrations of sitosterol were significantly higher in both normocholesterolemic and hypercholesterolemic patients with primary biliary cirrhosis as compared with the respective controls ( P Ͻ 0.01). In patients with primary biliary cirrhosis, serum 7 ␣hydroxycholesterol was slightly higher than in controls. 27-Hydroxycholesterol was significantly higher in hypercholesterolemic compared to normocholesterolemic controls ( P Ͻ 0.05) and a significant linear correlation ( r ‫؍‬ 0.771; P Ͻ 0.001) was found between 27-hydroxycholesterol and cholesterol. In contrast, in patients with primary biliary cirrhosis, high cholesterol concentrations were not associated with increased serum levels of 27-hydroxycholesterol. Our data confirm that in patients with primary biliary cirrhosis, cholesterol synthesis and biliary elimination of sterols are impaired and also suggest that both the feedback regulation of retained bile acids on cholesterol 7 ␣ -hydroxylase and the scavenger effect on elevated serum cholesterol by cholesterol 27-hydroxylase are deficient in these patients.

Interactions of Oxysterols with Atherosclerosis Biomarkers in Subjects with Moderate Hypercholesterolemia and Effects of a Nutraceutical Combination (Bifidobacterium longum BB536, Red Yeast Rice Extract) (Randomized, Double-Blind, Placebo-Controlled Study)

“…Oxysterols were analyzed as previous described [21] using a Thermofinnigan GC-Q instrument supplied with an ion trap source. Oxysterols separation was obtained with an HP5 (Agilent, Lexington, MN, USA) capillary column 0.25 mm i.d., 0.25 µm film thickness, 30 m length, operating at 1 mL/min helium flow rate.…”

“…Ions were recorded at m/z 353 for 19-hydroxycholesterol and m/z 462 for deuterated 27-OHC (internal standards), m/z 456 for 27-and 25-OHC and m/z 413 for 24-OHC. Endogenous hydroxysterol concentrations were calculated with a standard curve, prepared as described [21], and the peak area ratio (sterol/IS) found in the sample. Noteworthy, in the literature the same chemical compound is called both 26-OHC and 27-OHC [22].…”

Cholesterol metabolism in primary biliary cirrhosis during simvastatin and UDCA administration

“…Deuterated lathosterol (1 g) and 5 ␣ -cholestane (1 g) were added to 0.1 ml serum samples as internal standards for the measurement of lathosterol and dietary sterols, respectively. After alkaline hydrolysis with 1 ml 1N NaOH in 90% ethanol at 60 Њ C for 90 min under nitrogen, samples were extracted, transformed into trimethylsilylimidazole (TMS) derivatives, and analyzed as described previously (7).…”

“…After addition of 250 ng of 19-hydroxycholesterol as internal standard to 0.2 ml serum, samples were hydrolyzed and extracted as described (7). The organic phase was evaporated to dr yness under a stream of nitrogen and purified by solid phase extraction.…”

“…Both synthesis and biliary elimination of cholesterol are impaired (4,5), with concomitant reduction of serum levels of lathosterol and increased serum concentrations of dietary sterols, such as campesterol (4,5). In addition, reduced cholesterol absorption may occur in patients with the latest stage of the disease (5), and data from a recent study suggest that both the feedback regulation of retained bile acids on cholesterol 7 ␣ -hydroxylase and the cholesterol 27hydroxylase scavenger effect on excess serum cholesterol are deficient in these patients (7).…”