Resveratrol for protection against statin toxicity in C2C12 and H9c2 cells

Rezkallah, Chama Attalah nee; Thongkum, Angkana; Zhu, Chao; Chen, Qin M.

doi:10.1002/jbt.22484

Cited by 4 publications

(2 citation statements)

References 48 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…For most people, statins are safe and well tolerated. However, 30% of statins have been associated with intolerance, including the most prevalent muscle and liver toxicities [ 57 ]. The strengthening of childhood hypercholesterolemia screening has increased the use of statins in children [ 58 ].…”

Section: Discussionmentioning

confidence: 99%

Simvastatin Inhibits NLRP3 Inflammasome Activation and Ameliorates Lung Injury in Hyperoxia-Induced Bronchopulmonary Dysplasia via the KLF2-Mediated Mechanism

Wang

Huo

Liang

et al. 2022

Oxidative Medicine and Cellular Longevity

View full text Add to dashboard Cite

Bronchopulmonary dysplasia (BPD) is a chronic lung disease commonly found in premature infants. Excessive inflammation and oxidative stress contribute to BPD occurrence and development. Simvastatin, as an inhibitor of HMG-CoA reductase, has been reported to have antioxidative and anti-inflammatory effects. However, its effect and possible mechanisms in hyperoxia-induced lung injury are rarely reported. In this study, in vivo and in vitro experiments were conducted to investigate whether simvastatin could ameliorate hyperoxia-induced lung injury and explore its potential mechanism. For the in vivo study, simvastatin could improve alveolar development after hyperoxic lung injury and reduce hyperoxic stress and inflammation. The in vitro study revealed that simvastatin can reduce inflammation in A549 cells after high-oxygen exposure. Simvastatin suppressed NLRP3 inflammasome activation and played anti-inflammatory and antioxidant roles by increasing KLF2 (Krüppel-like factor 2) expression. In vitro experiments also revealed that these effects of simvastatin were partially reversed by KLF2 shRNA, indicating that KLF2 was involved in simvastatin effects. In summary, our findings indicate that simvastatin could downregulate NLRP3 inflammasome activation and attenuate lung injury in hyperoxia-induced bronchopulmonary dysplasia via KLF2-mediated mechanism.

show abstract

Section: Discussionmentioning

confidence: 99%

Simvastatin Inhibits NLRP3 Inflammasome Activation and Ameliorates Lung Injury in Hyperoxia-Induced Bronchopulmonary Dysplasia via the KLF2-Mediated Mechanism

Wang

Huo

Liang

et al. 2022

Oxidative Medicine and Cellular Longevity

View full text Add to dashboard Cite

show abstract

“…Statins can cause many side effects while treating various diseases. The side effects of statins include liver toxicity [65], muscle toxicity [66] and neurotoxicity [67], as well as the following: effects on coenzyme Q10 and the mitochondrial membrane [68,69]; effects on isopentenyl and glycosylase, and effects on ion channel signaling [70]. The dysfunction of cellular metabolism further leads to various adverse effects.…”

Section: Discussionmentioning

confidence: 99%

Pleiotropic use of Statins as non-lipid-lowering drugs

Zhang¹,

Dong²,

2020

Int. J. Biol. Sci.

View full text Add to dashboard Cite

Statins, known as HMG-CoA reductase (HMGCR) inhibitors, have primarily been utilized for metabolic and angiographic medical applications because of their cholesterol-lowering effects. Similar to other drugs, statins may also induce a series of potential side effects. Statins inhibit the HMGCR (rate-limiting enzyme) activity in early stages of mevalonate pathway and then indirectly affect a number of intermediate products, including non-sterol isoprenoids (coenzyme Q10, dolichol etc.), which can result in impaired functions of body organs. Recently, scores of studies have uncovered additional functional mechanisms of statins in other diseases, such as diabetes mellitus, nervous system diseases, coronary heart disease, inflammation and cancers. This review aims to summarize the positive and adverse mechanisms of statin therapy. Statin care should be taken in the treatment of many diseases including cancers. Since the underlying mechanisms are not fully elucidated, future studies should spend more time and efforts on basic research to explore the mechanisms of statins.

show abstract

Prolonged treatment of compactin, atorvastatin, lovastatin or simvastatin decreased glucose consumption and expressions of proteins for glucose metabolism and insulin signaling in L6 skeletal muscle cells

Chen,

Zha,

et al. 2024

Food Nutr. Health

View full text Add to dashboard Cite

Statins inhibit mevalonate synthesis and successfully lower plasma cholesterol levels and decrease the risk of cardiovascular diseases in humans, but also lead to myalgia in some patients. We hypothesize that statins may modulate glucose metabolism and insulin signaling in the skeletal muscle cells during and after differentiation, and in turn lead to side effects. Here, differentiating and differentiated L6 muscle cells were treated with 1 μM of different class of statins (compactin, pravastatin, atorvastatin, lovastatin and simvastatin) with or without insulin or mevalonate for extended periods of time. The glucose consumption and expression levels of proteins for glucose metabolism and insulin receptor (IR)/Akt signaling were determined. The prolonged statin treatments (except pravastatin) decreased glucose consumption in L6 skeletal muscle cells. In differentiating L6 cells, compactin, lovastatin or simvastatin decreased the expression levels of proteins involved in glucose metabolism and insulin signaling, including glucose transporter 4 (GLUT4), pyruvate dehydrogenase (PDH), glycogen synthase (GS), glycogen synthase kinase 3β (GSK3β) and insulin receptor β subunit (IRβ). In differentiated L6 cells, long-term treatment of compactin or simvastatin also decreased levels of proteins in glucose metabolism and IR/Akt signaling, including GLUT4, GSK3β, IRβ and PI3K p110α. Insulin treatment restored statin-mediated impairments in L6 cells. The insulin-mediated phosphorylation of Akt Ser473 was attenuated in differentiating and differentiated L6 cells in the presence of atorvastatin (differentiated only), compactin, lovastatin or simvastatin. In addition, mevalonate supplementation reversed the statin-mediated impairments in differentiated and differentiating L6 cells. Statin affected glucose usage and insulin signaling by inhibiting mevalonate synthesis in L6 cells. Our results provides a possible mechanism of adverse effects of statins in skeletal muscle and calls for cautious use of the medication in patients with impaired insulin sensitivity and glucose metabolism.

show abstract

Resveratrol for protection against statin toxicity in C2C12 and H9c2 cells

Cited by 4 publications

References 48 publications

Simvastatin Inhibits NLRP3 Inflammasome Activation and Ameliorates Lung Injury in Hyperoxia-Induced Bronchopulmonary Dysplasia via the KLF2-Mediated Mechanism

Simvastatin Inhibits NLRP3 Inflammasome Activation and Ameliorates Lung Injury in Hyperoxia-Induced Bronchopulmonary Dysplasia via the KLF2-Mediated Mechanism

Pleiotropic use of Statins as non-lipid-lowering drugs

Prolonged treatment of compactin, atorvastatin, lovastatin or simvastatin decreased glucose consumption and expressions of proteins for glucose metabolism and insulin signaling in L6 skeletal muscle cells

Contact Info

Product

Resources

About