BackgroundThe baseline incidence of the adverse events of statin therapy varies between countries. Notably, Chinese patients seem more susceptible to myopathy induced by simvastatin.ObjectivesThis research studies the adverse drug reactions (ADRs) of statin therapy in China by analysing trial-based data from the Anti-hyperlipidaemic Drug Database built by the China National Medical Products Administration Information Centre.MethodsAll clinical trials involving statin therapy (including simvastatin, atorvastatin, fluvastatin, lovastatin, pravastatin and rosuvastatin) in China from 1989 to 2019 were screened. In total, 569 clinical studies with 37 828 patients were selected from 2650 clinical trials in the database.ResultsAmong the reported cases with ADRs (2822/37 828; 7.460%), gastrointestinal symptoms were the most common (1491/37 828; 3.942%), followed by liver disease (486/37 828; 1.285%), muscle symptoms (444/37 828; 1.174%) and neurological symptoms (247/37 828; 0.653%). Pravastatin (231/1988; 11.620%) caused the most common gastrointestinal side effects, followed by fluvastatin (333/3094; 10.763%). The least likely to cause gastrointestinal irritation was rosuvastatin (82/1846; 4.442%).ConclusionIn Chinese clinical trials, gastrointestinal symptoms were the most common ADR of statin use for hyperlipidaemia and other cardiovascular diseases.
Background3-(5'-Hydroxymethyl-2'-furyl)-1-benzylindazole (YC-1) is a potential anticancer drug that may activate soluble guanylyl cyclase (sGC) and increase the level of cyclic guanosine monophosphate (cGMP). The aim of this study was to explore the effects of YC-1 on lipid droplet accumulation and foam cell formation in macrophages.ResultsHuman-oxidized low density lipoprotein (ox-LDL) was used to induce accumulation of lipid droplets in a murine macrophage cell line, RAW 264.7. Oil red O staining showed that treatment with 20 μM YC-1 for 24 h increased the area of intracellular lipid droplets in macrophages. The results of high content screening (HCS) with the AdipoRed™ assay further revealed that YC-1 enhanced ox-LDL-induced foam cell formation. This was evidenced by an increase in the total area of lipid droplets and the mean fluorescence intensity per cell. Inhibition of cGMP-dependent protein kinase (PKG) using KT5823 significantly reduced YC-1-enhanced lipid droplet formation in ox-LDL-induced macrophage foam cells.ConclusionYC-1 induces lipid droplet formation in macrophages, possibly through the sGC/cGMP/PKG signaling pathway. This chemical should be tested with caution in future clinical trials.
ObjectiveThis study aims to understand the adverse drug reactions (ADRs) for non-statin antihyperlipidaemic drugs included in the China Anti-hyperlipidemic Drug Database.DesignAn approach of Chinese national database analysis was employed to screen clinical trials involving non-statin antihyperlipidaemic drugs from 1989 to 2019.SettingThe database was provided by the China National Medical Products Administration Information Centre.ParticipantsIn total, 117 clinical studies with 8800 patients were selected from 2650 clinical trials of the Anti-hyperlipidemic Drug Database.InterventionsThe non-statin antihyperlipidaemic drugs were divided into three groups: (1) fibrates (fenofibrate, gemfibrozil, bezafibrate, etofylline clofibrate); (2) nicotinic acid and derivatives (niacin, acipimox) and (3) others (probucol, cholestyramine).ResultsThe results of this study show that first, gastrointestinal symptoms were the most common reactions (6.975%), which account for approximately 50% of the reported cases with ADRs. Second, cholestyramine (16.418%) and gemfibrozil (13.158%) were the most common gastrointestinal side effect-causing non-statin antihyperlipidaemic drugs, which account for one-third of the population. Third, niacin (7.879%) and gemfibrozil (5.000%) were the most likely cause of liver disease symptoms. Finally, niacin (10.909%) and acipimox (18.847%) were the major non-statin antihyperlipidaemic drugs with skin symptoms.ConclusionThis study revealed that gastrointestinal symptoms were the most common ADRs of fibrates, probucol and cholestyramine in the Chinese population. For nicotinic acid and derivatives, the ADRs of skin symptoms were the most common in China.
Macrophages would engulf circulating oxidized (ox)-lowdensity lipoprotein and form lipid droplet-laden foam cells. Macrophage foam cells are considered an important therapeutic target of atherosclerosis. The aim of the study was to investigate a hypoxic foam cell model for anti-atherosclerotic drug screening using the chemical hypoxia-mimicking agent cobalt chloride (CoCl 2). The oil red O stating results showed that treatment with CoCl 2 could induce lipid accumulation and lead to cell transformation to spindle-shaped and lipid-rich foam cells in RAW 264.7 macrophages. Incubation with 150 lM CoCl 2 for 24 h significantly increased the area of intracellular lipid droplets in macrophages, compared with the control group. Our findings indicate that CoCl 2-triggered macrophage foam cells should be a potential in vitro hypoxia model for atherosclerosis drug discovery.
Lipid metabolism in visceral fat cells is correlated with metabolic syndrome and cardiovascular diseases. Okadaic-acid, a 38-carbon fatty acid isolated from the black sponge Halichondria okadai, can stimulate lipolysis by promoting the phosphorylation of several proteins in adipocytes. However, the mechanism of okadaic acid-induced lipolysis and the effects of okadaic acid on lipid-droplet-associated proteins (perilipins and beta-actin) remain unclear. We isolated adipocytes from rat epididymal fat pads and treated them with isoproterenol and/or okadaic acid to estimate lipolysis by measuring glycerol release. Incubating adipocytes with okadaic acid stimulated time-dependent lipolysis. Lipid-droplet-associated perilipins and beta-actin were analyzed by immunoblotting and immunofluorescence, and the association of perilipin A and B was found to be decreased in response to isoproterenol or okadaic acid treatment. Moreover, okadaic-acid treatment could enhance isoproterenol-mediated lipolysis, whereas treatment of several inhibitors such as KT-5720 (PKA inhibitor), calphostin C (PKC inhibitor), or KT-5823 (PKG inhibitor) did not attenuate okadaic-acid-induced lipolysis. By contrast, vanadyl acetylacetonate (tyrosine phosphatase inhibitor) blocked okadaic-acid-dependent lipolysis. These results suggest that okadaic acid induces the phosphorylation and detachment of lipid-droplet-associated perilipin A and B from the lipid droplet surface and thereby leads to accelerated lipolysis.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.