Hepatic responses to inhibition of 3-hydroxy-3-methylglutaryl-CoA reductase: a comparison of atorvastatin and simvastatin

Bergstrom, James D.; Bostedor, Richard G.; Rew, Deborah J.; Geissler, Wayne M.; Wright, Samuel D.; Chao, Yu‐Sheng

doi:10.1016/s0005-2760(97)00182-3

Cited by 42 publications

(32 citation statements)

References 33 publications

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“…This result is consistent with the study done by Bergstrom et al (1998), who reported that atorvastatin and simvastatin caused inhibition of HMG-CoA reductase activity in Hep G2 cells. Similar findings was reported by Wilcox et al (1999) who demonstrated that supplementation of 10 µM simvastatin decreased cellular cholesterol synthesis and CE mass in Hep G2 cell by up to 96% (P < 0.001) and 52% (P < 0.001), respectively and furthermore these inhibitors have been widely used to lower plasma cholesterol levels.…”

Section: Results Insupporting

confidence: 93%

Effects of Tinospora crispa aqueous extract in regulating cholesterol metabolism in human hepatoma cancer cell line (Hep G2)

Shah¹,

Hasan²,

Arshad³

et al. 2017

J. Med. Plants Res.

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In this study, the ability of Tinospora crispa aqueous extract (TCAE) to regulate cholesterol metabolism in human hepatoma cancer cell line (Hep G2) was determined. Cytotoxic study was performed by exposing hepatoma cell (Hep G2) towards TCAE with concentration ranging from 0.002 to 20 mg/ml for 24 h at 37°C and with 5% CO 2 atmosphere. Result revealed that TCAE was not toxic to the cell. The ability of TCAE to reduce cholesterol in cell culture experiment was carried out by pre-treating Hep G2 with selected concentrations of TCAE (10, 5, 2.5, 1.25 and 0.625 mg/ml) in 6-well plate before the cell was exposed to low density lipoprotein (LDL). The concentration of apolipoprotein A1 (Apo A1), lecithin-cholesterol acyltransferase (LCAT), low density lipoprotein receptor (LDLR), scavenger receptor B1 (SRB1) and hepatic Lipase (HL) which involve in reverse cholesterol transport (RCT) pathway were determined from the 6-well plate medium. The direct pathway of cholesterol synthesis was performed according to the instruction provided in HMG-CoA Reductase Assay Kit manuals. The results showed that TCAE significantly increase (p<0.05) the concentration of Apo A1, LCAT, LDLR, SRB-1 and HL. The efficacy of these activities is appreciably good when compared with standard drug simvastatin. However, TCAE showed moderate effect in controlling mevalonate pathway. These findings suggested that TCAE has the potential to reduce cholesterol metabolism in Hep G2 cancer cell lines and the pathway of TCAE action possibly more on RCT.

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Section: Results Insupporting

confidence: 93%

Effects of Tinospora crispa aqueous extract in regulating cholesterol metabolism in human hepatoma cancer cell line (Hep G2)

Shah¹,

Hasan²,

Arshad³

et al. 2017

J. Med. Plants Res.

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“…The reduced efficacy of statins in rodents compared with humans has been explained by the fact that statins primarily control levels of LDL cholesterol, which is compared with HDL a minor component in plasma lipoproteins of mice (47). The inhibition of cholesterol synthesis by statins has been described in numerous cell culture studies (19,48). Assuming that this effect can be translated to in vivo conditions, cholesterol synthesis is rarely measured in experiments in humans or rodent models.…”

Section: Discussionmentioning

confidence: 99%

“…They reported that cholesterol synthesis was even increased in pravastatin-treated individuals compared with controls. Furthermore, increased hepatic Hmgcr mRNA and enzyme activity levels have been observed in biopsies of humans and in various animal models treated with statins (18)(19)(20)(21)(22)(23)(24). Combined, these data challenge the current dogma that decreased cholesterol synthesis underlies the reduction of plasma cholesterol levels achieved by statin treatment.…”

Section: C-acetate Methodsmentioning

confidence: 99%

Statins increase hepatic cholesterol synthesis and stimulate fecal cholesterol elimination in mice

Schonewille

Boer

Mele

et al. 2016

Journal of Lipid Research

114

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“…Therefore, a different set of five control animals was paired with each group of five animals on the experimental diets to eliminate any possible seasonal effects. At the start of the experimental feeding period, each treatment group of animals was switched to powdered diet to which was added either 0.5% (wt/wt) fenofibrate (21) or 0.05% simvastatin (22). The fish-oil and corn-oil diets were based on the isocaloric high-fat diets described in Pegorier et al (23), containing 30% by weight of menhadden oil or corn oil, respectively.…”

Section: Materials Radiolabeled 1-[mentioning

confidence: 99%

Differential Effects of Fenofibrate or Simvastatin Treatment of Rats on Hepatic Microsomal Overt and Latent Diacylglycerol Acyltransferase Activities

Waterman

Zammit²

2002

Diabetes

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Hepatic triacylglycerol secretion is elevated in insulinresistant states. Microsomal diacylglycerol acyltransferase (DGAT) catalyzes the final reaction in the synthesis of triacylglycerol (TAG). We have previously described two DGAT activities in rat liver microsomes, one overt (cytosol-facing) and one latent (endoplasmic reticulum lumen-facing) (Owen MR, Corstorphine CG, Zammit VA: Overt and latent activities of diacylglycerol acytransferase in rat liver microsomes: possible roles in verylow-density lipoprotein triacylglycerol secretion. Biochem J 323:17-21, 1977). It was suggested that they are involved in the synthesis of TAG for the cytosolic droplet and VLDL lipidation, respectively. In the present study, we measured the overt and latent DGAT activities in rats fed diets containing one of two hypolipidemic drugs: fenofibrate (a peroxisome proliferator-activated receptor ␣ [PPAR␣] agonist) and simvastatin (a 3-hydroxy-3-methylglutaryl [HMG]-CoA reductase inhibitor). We found that the activities of the two DGATs could be varied independently by these treatments. Fenofibrate raised overt DGAT activity but lowered that of latent DGAT. In contrast, simvastatin markedly lowered overt DGAT activity without affecting that of latent DGAT. The increase in overt DGAT activity induced by fenofibrate could not be mimicked by feeding a diet enriched in n-3 polyunsaturated fatty acids (PUFA), which lowered overt DGAT activity but did not affect latent DGAT, suggesting that n-3 PUFA act through a mechanism independent of PPAR␣ activation. The fibrate-induced increase in overt DGAT activity and the inhibition of latent DGAT may provide a mechanism through which acyl moieties are retained within the liver for oxidation through the pathways concomitantly upregulated by PPAR␣ activation.

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Hepatic responses to inhibition of 3-hydroxy-3-methylglutaryl-CoA reductase: a comparison of atorvastatin and simvastatin

Cited by 42 publications

References 33 publications

Effects of Tinospora crispa aqueous extract in regulating cholesterol metabolism in human hepatoma cancer cell line (Hep G2)

Effects of Tinospora crispa aqueous extract in regulating cholesterol metabolism in human hepatoma cancer cell line (Hep G2)

Statins increase hepatic cholesterol synthesis and stimulate fecal cholesterol elimination in mice

Differential Effects of Fenofibrate or Simvastatin Treatment of Rats on Hepatic Microsomal Overt and Latent Diacylglycerol Acyltransferase Activities

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