The mechanism of lack of hypocholesterolemic effects of pravastatin sodium, a 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor, in rats

Fujioka, Tomoyuki; Nara, Futoshi; Tsujita, Yasuyuki; Fukushige, Junichiro; Fukami, Masaharu; Kuroda, Masao

doi:10.1016/0005-2760(94)00154-q

Cited by 91 publications

(60 citation statements)

References 22 publications

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“…In the agreement with us, Fujioka et al (1995) did not observe any effect of statins on plasma level of total cholesterol as well as LDL-cholesterol in normolipidemic rats. On the other hand, it was shown that fibrates possess hypocholesterolemic (Krause and Princen 1998) and hypotriglyceridemic (Frøyland et al 1997) effects in rats.…”

Section: Discussionsupporting

confidence: 92%

“…On the other hand, it was shown that fibrates possess hypocholesterolemic (Krause and Princen 1998) and hypotriglyceridemic (Frøyland et al 1997) effects in rats. An explanation for this discrepancy may be a dosage of fibrates (10-500 mg/kg) usually used in other experimental studies (Fujioka et al 1995;Alegret et al 1998) and highly exceeding the recommended daily dosage for human which was given in our study (0.3 mg/kg).…”

Section: Discussioncontrasting

confidence: 65%

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Hypolipidemic Drugs Can Change the Composition of Rat Brain Lipids

Vecka

Tvrzická

Staňková

et al. 2004

Tohoku J. Exp. Med.

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Hypolipidemic drugs are potent serum cholesterol lowering agents used for prevention of coronary heart disease. In addition to their cholesterol lowering effect, these drugs exhibit both pleiotropic beneficial and various neurological side effects. Therefore, we analysed effect of the hypolipidemic drugs, fenofibrate and statins, on membrane lipid composition in the rat brain tissue. Male Wistar rats were given 0.1 mg of fenofibrate, lovastatin, pravastatin, fluvastatin or placebo (control) once daily for six weeks. In rats treated with lovastatin or pravastatin, decreased cholesterol and increased ceramide monohexoside contents in the brain tissue were observed in comparison with control. Treatment with fluvastatin or lovastatin resulted in increased sphingomyelin and decreased diphosphatidylglycerol contents. The most important changes in the fatty acid profile were observed in ceramide monohexosides; treatment with fluvastatin decreased the content of saturated and increased the content of polyunsaturated fatty acids. Fenofibrate treatment led to decreased content of saturated fatty acids in phosphatidylethanolamines. In conclusion, statin treatment resulted in the decreased content of cholesterol and diphosphatidylglycerol associated with the increased content of sphingolipids in the rat brain tissue. As cholesterol and sphingolipids are important components of brain membranes, the observed alterations in the composition brain lipids might be involved in genesis of neurological and mental symptoms following statin therapy.statin; fibrate; brain; lipids; fatty acid

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Section: Discussionsupporting

confidence: 92%

Section: Discussioncontrasting

confidence: 65%

Hypolipidemic Drugs Can Change the Composition of Rat Brain Lipids

Vecka

Tvrzická

Staňková

et al. 2004

Tohoku J. Exp. Med.

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“…In the current study, treatment with pravastatin inhibited markedly the L-NAME-induced high total and LDL cholesterol levels although statins are demonstrated to have no lipid lowering effects in rats even at high doses (34). Triglyceride levels were also decreased with pravastatin treatment, but no effect was observed in HDL levels in this study.…”

Section: Discussioncontrasting

confidence: 57%

The anti-inflammatory and antioxidant effects of pravastatin and nebivolol in rat aorta

Dursun¹,

Çuhadar²,

Köseoğlu³

et al. 2014

Anadolu Kardiyol Derg

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Objective: The aim of this study was to investigate the effects of pravastatin and nebivolol in the atherosclerotic process including inflammation and oxidative stress in rat aorta. Methods: This experimental randomized controlled study comprised of 35 Wistar albino rats. N ω -nitro-L-arginine methyl ester (L-NAME) -induced vascular inflammation and arteriosclerosis were treated with both of the pharmacologic agents. All were divided into 5 equal groups: the control, group I: L-NAME -15 days, group II: L-NAME 30+ nebivolol, group III: L-NAME -30+ pravastatin, group IV: L-NAME -30 days. Serum ceruloplasmin, uric acid, total antioxidant capacity (TAC), total cholesterol (T.Chol), low density lipoprotein (LDL), high density lipoprotein (HDL), triglyceride (TG) were analyzed. Medial thickening and leukocyte infiltration status were examined histopathologically. The results were compared with control group and with each other using Kruskal-Wallis and Mann-Whitney U test. Results: Pravastatin diminished the rise of ceruloplasmin, which was taken as an index of inflammation (p=0.002). Pravastatin and nebivolol decreased the L-NAME induced oxidative stress (p=0.001, 0.002, respectively). Nebivolol diminished the rise of LDL (p=0.04). Pravastatin lowered T.Chol, LDL and TG levels (p=0.001, 0.008, 0.040, respectively). HDL values were not changed significantly. Conclusion: In conclusion, 15 days of statin therapy attenuated vascular inflammation and lowered the rised lipid levels (LDL, T.cholesterol and TG). Both the nebivolol and pravastatin exhibited antioxidant property. These documented beneficial effects of both of the drugs may improve the clinical outcomes of patients with hypertension or hyperlipidemia by additional studies. (Anadolu Kardiyol Derg 2014; 14: 229-33)

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“…It is known that the effect of HMG CoA reductase inhibitors is diverse in different animal species (23,24). For instance, compactin or pravasta tin, an HMG-CoA reductase inhibitor, effectively sup presses the enzyme in humans and rabbits, and results in decreasing their serum TC levels, but it fails to exhibit the action in rats (25)(26)(27). Such species specificity is likely to be the cause of the lack of G-hesperidin action in humans.…”

Section: Discussionmentioning

confidence: 99%

Effects of Glucosyl Hesperidin on Serum Lipids in Hyperlipidemic Subjects: Preferential Reduction in Elevated Serum Triglyceride Level

Miwa

Yamada

Sunayama

et al. 2004

Journal of Nutritional Science and Vitaminology, J Nutr Sci Vit

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SummaryAlthough hesperidin lowers serum total cholesterol (TC) or triglyceride (TG) in animal models, its effect in humans remains unclear. Using a soluble hesperidin derivative, glucosyl hesperidin (G-hesperidin), as a hesperidin source, we examined the efficacy on hyperlipidemic subjects. G-Hesperidin was administered to the subjects at 100 or 500mg/d for 6wk. The percentage of subjects who had a change in serum cholesterol levels was less than 20%. However, 45-55% of the total subjects showed a reduction in serum TG level. The subjects were classified into normal (TC<230mg/dL, TG<150mg/dL), high-TC (TC>230mg/dL, TG<150mg/dL) and high-TG (TG>150mg/dL) types. While serum cho lesterol levels scarcely changed in any phenotype, TG level was significantly reduced by administration in the high-TG type. In this phenotype, serum apolipoprotein (apo) C-II and E levels decreased by the administration, but non-apo B. G-Hesperidin also raised low-den sity lipoprotein (LDL)-cholesterollapo B in the high-TG type. These results indicate that G hesperidin preferentially lowers serum TG in hypertriglyceridemic subjects and that this effect is possibly caused by the facilitation of catabolism of TG-rich lipoproteins and may contribute to the reduction of small dense LDL.

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The mechanism of lack of hypocholesterolemic effects of pravastatin sodium, a 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor, in rats

Cited by 91 publications

References 22 publications

Hypolipidemic Drugs Can Change the Composition of Rat Brain Lipids

Hypolipidemic Drugs Can Change the Composition of Rat Brain Lipids

The anti-inflammatory and antioxidant effects of pravastatin and nebivolol in rat aorta

Effects of Glucosyl Hesperidin on Serum Lipids in Hyperlipidemic Subjects: Preferential Reduction in Elevated Serum Triglyceride Level

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