Abstract
Statins such as simvastatin have many side effects, including muscle damage, which is known to be the most frequent undesirable side effect. Lysophosphatidic acid (LPA), a kind of biolipid, has diverse cellular activities, including cell proliferation, survival, and migration. However, whether LPA affects statin-linked muscle damage has not been reported yet. In the present study, to determine whether LPA might exert potential protective effect on statin-induced myocyotoxicity, the effect of LPA on cytotoxicity in rat L6 myoblasts exposed to simvastatin was explored. Viability and apoptosis of rat L6 myoblasts were detected via 2,3-bis(2-methoxy-4-nitro-5-sulfophenyl)-5- [(phenylamino)carbonyl]-2H-tetrazolium hydroxide (XTT) assay and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) assay, respectively. Protein expression levels were detected via Western blotting. Simvastatin decreased viability of L6 cells. Such decrease in viability was recovered in the presence of LPA. Treatment with LPA suppressed simvastatin-induced apoptosis in L6 cells. In addition, treatment with LPA receptor inhibitor Ki16425, protein kinase C (PKC) inhibitor GF109203X, or intracellular calcium chelator BAPTA-AM attenuated the recovery effect of LPA on simvastatin-induced L6 cell toxicity. These findings indicate that LPA may inhibit simvastatin-induced toxicity in L6 cells probably by activating the LPA receptor-PKC pathway. Therefore, LPA might have potential as a bioactive molecule to protect muscles against simvastatin-induced myotoxicity.
Highlights
The effect of Lysophosphatidic acid (LPA) on simvastatin-reduced L6 cell viability was examined in L6 cells treated with different concentrations of LPA in the presence of 10 and μM significantly reduced simvastatin (10 μM) of simvastatin
In the presence of 10 μM of simvastatin, treatment with LPA at 1–30 μM dose-dependently increased the viability of L6 cells
Statins are very effective for treating patients with hypercholesterolemia
Summary
They have been widely used for treating hyperlipidemia [1,2,3] and decreasing cardiovascular risk [2,4,5]. Statins such as pravastain, fluvastatin, lovastatin, atrovastatin, rosuvastatin, simvastatin, and so on are known to be able to decrease the synthesis of cholesterol by inhibiting 3-hydroxy-3-methylglutaryl coenzyme A Statins can induce reactive oxidative stress that could result in cell death [9,10,11]. They may experience clinical adverse effects such as hepatotoxicity, diabetes mellitus, and skeletal muscle
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