Effects of simvastatin on malondialdehyde level and esterase activity in plasma and tissue of normolipidemic rats

Macan, Marija; Vukšić, Antonija; Žunec, Suzana; Konjevoda, Paško; Lovrić, Jasna; Kelava, Marta; Štambuk, Nikola; Vrkić, Nada; Bradamante, Vlasta

doi:10.1016/j.pharep.2015.02.005

Cited by 13 publications

(17 citation statements)

References 34 publications

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“…To date, many hypolipidemic drugs have been used to control serum cholesterol levels and to prevent hyperlipidemia. Among these drugs, statins are widely used to retard the atherosclerosis in patients with hyperlipidemia (Macan et al, 2015). In fact, these drugs have also been reported to present anti-inflammatory, anticancer, antioxidant and immunomodulatory effects (Chen et al, 2018;Rizvi et al, 2019).…”

Section: Introductionmentioning

confidence: 99%

The Effect of Simvastatin on Gut Microbiota and Lipid Metabolism in Hyperlipidemic Rats Induced by a High-Fat Diet

et al. 2020

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The objective of this study was to investigate the effects of simvastatin (SIM) on lipid metabolism disorders and gut microbiota in high-fat diet-induced hyperlipidemic rats. The obtained results revealed that feeding rats with SIM (20 mg/kg/day) significantly decreased serum lipid level and inhibited hepatic lipid accumulation and steatosis. Histological analysis further indicated that SIM reduced lipid deposition in adipocytes and hepatocytes in comparison with that of the HFD group. The underlying mechanisms of SIM administration against HFD-induced hyperlipidemia were also studied by UPLC-Q-TOF/MS-based liver metabonomics coupled with pathway analysis. Metabolic pathway enrichment analysis of liver metabolites with significant difference in abundance indicated that fatty acids metabolism and amino acid metabolism were the main metabolic pathways altered by SIM administration. Meanwhile, operational taxonomic units (OTUs) analysis revealed that oral administration of SIM altered the composition of gut microbiota, including Ruminococcaceae (OTU960) and Lactobacillus (OTU152), and so on. Furthermore, SIM treatment also regulated the mRNA levels of the genes involved in lipid and cholesterol metabolism. Immunohistochemistry (IHC) analysis of the liver-related proteins (CD36, CYP7A1 and SREBP-1C) showed that oral administration of SIM could regulate the levels of the protein expression related to hepatic lipid metabolism.

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Section: Introductionmentioning

confidence: 99%

The Effect of Simvastatin on Gut Microbiota and Lipid Metabolism in Hyperlipidemic Rats Induced by a High-Fat Diet

et al. 2020

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“…Previous studies conveyed that the metabolism of SV is complex and involves the oxidative biotransformation mainly by CYP3A [41,42]. Studies also indicated that SV can be hydrolyzed to SVA by esterases, paraoxonases or through chemical approaches [43,44]. UGTs, especially UGT1A1 and UGT1A3, were also found as SV metabolizing proteins which catalyze the formation of glucuronide conjugates of SVA and its reversible conversion to SV [45].…”

Section: Discussionmentioning

confidence: 99%

Effects of Silymarin on the In Vivo Pharmacokinetics of Simvastatin and Its Active Metabolite in Rats

Liu¹,

Wu²,

Meng³

et al. 2019

Molecules

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Herein, the effect of silymarin pretreatment on the pharmacokinetics of simvastatin in rats was evaluated. To ensure the accuracy of the results, a rapid and sensitive UPLC–MS/MS method was established for simultaneous quantification of simvastatin (SV) and its active metabolite simvastatin acid (SVA). This method was applied for studying the pharmacokinetic interactions in rats after oral co-administration of silymarin (45 mg/kg) and different concentrations of SV. The major pharmacokinetic parameters, including Cmax, tmax, t1/2, mean residence time (MRT), elimination rate constant (λz) and area under the concentration-time curve (AUC0–12h), were calculated using the non-compartmental model. The results showed that the co-administration of silymarin and SV significantly increased the Cmax and AUC0–12h of SVA compared with SV alone, while there was no significant difference with regards to Tmax and t1/2. However, SV pharmacokinetic parameters were not significantly affected by silymarin pretreatment. Therefore, these changes indicated that drug-drug interactions may occur after co-administration of silymarin and SV.

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“…Several in vitro and in vivo non-clinical investigations have evidenced that statins either decrease or have no effect on AChE and BuChE activity (16,17). Our recent study, however, has shown that simvastatin significantly increases plasma and liver BuChE activity in normolipidemic rats (18). Fibrates have also been shown to increase BuChE activity in non-clinical studies (19,20).…”

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confidence: 89%

Effects of simvastatin and fenofibrate on butyrylcholinesterase activity in the brain, plasma, and liver of normolipidemic and hyperlipidemic rats

Vukšić

Lovrić

Konjevoda

et al. 2019

Archives of Industrial Hygiene and Toxicology

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The study objective was to test the hypothesis that simvastatin and fenofibrate should cause an increase in butyrylcholinesterase (BuChE) activity not only in the plasma and liver but also in the brain of normolipidemic and hyperlipidemic rats. Catalytic enzyme activity was measured using acetylthiocholine (ATCh) and butyrylthiocholine (BTCh) as substrates. Normolipidemic and hyperlipidemic rats were divided in four groups receiving 50 mg/kg of simvastatin a day or 30 mg/kg of fenofibrate a day for three weeks and three control groups receiving saline. Simvastatin and fenofibrate caused an increase in brain BuChE activity in both normo- and hyperlipidemic rats regardless of the substrate. The increase with BTCh as substrate was significant and practically the same in normolipidemic and hyperlipidemic rats after simvastatin treatment (14–17% vs controls). Simvastatin and fenofibrate also increased liver and plasma BuChE activity in both normolipidemic and hyperlipidemic rats regardless of the substrate. In most cases the increase was significant. Considering the important role of BuChE in cholinergic transmission as well as its pharmacological function, it is necessary to continue investigations of the effects of lipid-lowering drugs on BuChE activity.

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Effects of simvastatin on malondialdehyde level and esterase activity in plasma and tissue of normolipidemic rats

Cited by 13 publications

References 34 publications

The Effect of Simvastatin on Gut Microbiota and Lipid Metabolism in Hyperlipidemic Rats Induced by a High-Fat Diet

The Effect of Simvastatin on Gut Microbiota and Lipid Metabolism in Hyperlipidemic Rats Induced by a High-Fat Diet

Effects of Silymarin on the In Vivo Pharmacokinetics of Simvastatin and Its Active Metabolite in Rats

Effects of simvastatin and fenofibrate on butyrylcholinesterase activity in the brain, plasma, and liver of normolipidemic and hyperlipidemic rats

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