Abstract
Statins, the drugs for the treatment of dyslipidemia, have been suggested to impact insulin sensitivity, resulting in pancreatic β-cell dysfunction, and consequently, lead to new onset of diabetes. Taking this as a clue, the present study was designed to evaluate the protective effect of sesamol (a known antioxidant, antidiabetic and antidyslipidemic agent) against the diabetogenic potential of simvastatin. The toxic effects of simvastatin and sesamol on MIN6 insulinoma (Mouse pancreatic β cells) cells were evaluated separately by MTT assay. The protective effect of sesamol was evaluated at the IC50 value of simvastatin at doses ranging from 7.8 to 62.5 micromolar (µM). Further, the reversal of the impact of simvastatin on cell cycle and mitochondrial membrane potential by sesamol pretreatment was studied. The IC50 for simvastatin and sesamol were found to be 70.05 ± 2.34 μM and 2134 ± 8.41 μM, respectively, after 48 h and 72 h of incubation. Sesamol pretreatment protected the MIN6 cells from simvastatin toxicity (70 µM) in a dose-dependent manner from 7.8 to 31.25 µM. Simvastatin induced cell cycle arrest in G0/G1 phase. However, when cells were preincubated with sesamol for 24 h, a reversal in the cell cycle arrest was observed in simvastatin-treated cells (G0/G1). Pretreatment with sesamol also reduced the mitochondrial membrane potential loss compared to simvastatin treatment alone. These in vitro findings indicate that sesamol has a protective effect against simvastatin-induced toxicity on the pancreatic beta cells.
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Funding
This work was funded by the Science and Engineering Research Board (Grant number: Project File No. SERB/EMR/2017/003834-HS with diary no. SERB/F/7442/2018-2019 dated 24 September, 2018).
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Ghadge, G.A., Gourishetti, K., Chamallamudi, M.R. et al. Sesamol protects MIN6 pancreatic beta cells against simvastatin-induced toxicity by restoring mitochondrial membrane potentials. 3 Biotech 10, 149 (2020). https://doi.org/10.1007/s13205-020-2146-1
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DOI: https://doi.org/10.1007/s13205-020-2146-1