Hydroxytyrosol suppresses LPS-induced intrahepatic inflammatory responses via inhibition of ERK signaling pathway activation in acute liver injury.

OBJECTIVE: Acute liver injury (ALI) leads to inflammatory response and tissue damage. Inflammatory activation of infiltrative macrophages plays a critical role in liver histology destruction and dysfunction. Hydroxytyrosol (3,4-dihydroxyphenil-ethanol, HT), one of the polyphenols extracted from extra virgin olive oil, currently acts as a treatment for neuroinflammatory responses, but its effect on ALI is elusive. The present study aims to examine the mechanism of HT in macrophages inflammation and evaluate treatment effect of HT on ALI. MATERIALS AND METHODS: In vitro, the expressions of type M1/M2 macrophages biomarkers (CD11c/CD206) and cytokines (TNF-α, IL-1ß, IL-6, IL-10, IL-4) following lipopolysaccharide (LPS) stimulation and HT administration were detected using immunofluorescence, quantitative real-time polymerase chain reaction (qRT-PCR), and enzyme-linked immunosorbent assay (ELISA). Mechanically, HT was used to treat cells and phosphorylation level of extracellular-signal-regulated kinase 1/2 (ERK1/2) protein in cells was analyzed using Western blotting. In murine acute liver injury, inflammatory cytokines and liver injury degree were exhibited by qRT-PCR, IHC and HE staining. Furthermore, hepatic function was exhibited via hepatic metabolic enzymes (ALT/AST) and total bilirubin (TBil) in serum. RESULTS: It was demonstrated that HT treatment attenuated M1 macrophages and increased M2 macrophages after LPS stimulation. Furthermore, the pro-inflammatory cytokine level was descended, while an-inflammatory cytokine was increased via HT suppressing ERK pathway in macrophages. In vivo, HT reduced inflammatory level and mitigated hepatic histological injury, thus ameliorating liver function after acute liver injury. CONCLUSIONS: HT exerts a hepatoprotective and anti-inflammation effect on acute liver injury, which restrains inflammation by inhibiting ERK pathway and regulating macrophages polarization. Moreover, HT prevents liver tissues from inflammatory injury. Therefore, HT serves as a potential implication to treat ALI through modulating inflammation of macrophages.

Effects of diazepam (Valium) on aortic atherogenesis and plasma lecithin: cholesterol acyltransferase activity in cockerels fed an atherogenic diet.

Blood plasma LCAT (lecithin: cholesterol acyltransferase, EC 2.3.1.43) was studied in cockerels fed an atherogenic diet to determine if attenuation of aortic atherogenesis, as a result of simultaneous treatment of the birds with diazepam, might be related to modulation of enzyme activity by the drug. Administration of diazepam (0.6 mg/kg) did not influence LCAT. It was observed that no relationship could be established between enzyme activity and the extent of aortic atherogenesis. In contrast, addition of diazepam in vitro to cockerel plasma caused a concentration-dependent inhibition of LCAT activity. The effect was most pronounced when diazepam was present at a concentration of 50-200 microM, where inhibition of enzyme activity was 25-65%. Thus, pharmacologic doses of diazepam do not appear to affect LCAT in vivo. It is concluded that diazepam attenuates aortic atherogenesis in cockerels fed an atherogenic diet by a mechanism independent of LCAT.

The relationship between serum lipid levels and nutrient intake in healthy inhabitants of urban and rural Shanghai.

The serum lipid levels (mean +/- SD) of 3312 healthy urban and rural inhabitants over 40 years of age in Shanghai were studied. The results were: cholesterol 166.7 +/- 30.9 mg/ml, triglyceride 81.1 +/- 42.3 mg/dl, HDL-cholesterol (HDLc) 57.4 +/- 11.6 mg/dl, HDL2c 20.6 +/- 9.8 mg/dl and HDL3c 37.1 +/- 7.8 mg/dl. Dietary surveys were carried out in 512 of these subjects and their average daily nutrient intake was estimated to be: total calories 2,577 Kcal, proteins 656 g (50.7 g of vegetable proteins), fat 69.1 g (P/S ratio 0.70), carbohydrates 423 g, cholesterol 282 mg, dietary fibres 23.5 g, sodium 4993 mg, potassium 2,618 mg and magnesium 575 mg. The serum lipid levels of urban and rural inhabitants were compared. Total cholesterol levels were significantly higher in urban inhabitants of all age groups and of both sexes, while triglyceride levels were significantly higher in urban inhabitants of certain age groups. However, HDLc levels, particularly HDL2c levels were significantly higher in rural inhabitants of most age groups and of both sexes. The above differences were probably the result of differences in dietary patterns and nutrient intake between urban and rural inhabitants.