Low Glucose Enhances the Cytoprotective Effect of Metformin Against Doxorubicin Induced Cytotoxicity in Normal Cells

Abstract

The anti-diabetic drug, metformin, has been reported to be beneficial for the cardiovascular system and may facilitate the extension of a healthier lifespan. Doxorubicin is a leading chemotherapeutic drug used to treat a variety of cancers, yet it can cause significant adverse effects with cardiac toxicity and longterm damage. To test the hypothesis that the hypoglycaemic agent, metformin, may protect normal cells during chemotherapy treatment with liposomal doxorubicin, C2C12 myoblast cells were used to study cellular bioenergetics, variations in gene expressions and biochemical alterations induced by metformin and pegylated liposomal doxorubicin (L-Doxo) under low glucose conditions (2.7 mM or 50 mg/dL). Using confocal microscopy, we noted that treatment of C2C12 cells with 30 µg/mL L-Doxo under low glucose conditions induced a number of cellular defects. L-Doxo treatment dysregulated the expression of mitochondrial fission and fusion genes, which may influence transformation of the network’s connectivity. L-Doxo significantly reduced mitochondrial oxygen consumption rate (OCR) and extracellular acidification rate (ECAR). However, pre-treatment of cells with 100 nM metformin provided protection against L-Doxo-induced damage and increased cell viability and ATP levels in cells even under low glucose conditions. In addition, metformin increased and restored the decreased OCR and ECAR. Our data provide a mechanism by which low dose metformin exerts protective effects against L-Doxo via involvement of AMPKα under low glucose conditions. Taken together, our results demonstrate that metformin protects normal cells from L-Doxo damage even under low glucose conditions.

Adjusting the Dose of Ag-Ion Implantation on TiN–Ag-Modified SLA-Ti Creates Different Micronanostructures: Implications on Bacteriostasis, Biocompatibility, and Osteogenesis in Dental Implants

“…3 However, the increased surface roughness that promotes cell adhesion also adheres to bacteria, 4 leading to the accumulation of various bacteria that form biofilms on implant surfaces, which are generally considered to be a major predisposing factor for peri-implant infections. 5,6 Peri-implantitis is an inflammatory and destructive disease caused by the abnormal proliferation of different microbial flora around dental implants and has become the most serious complication that can lead to implant failure. 7−9 In addition, aseptic loosening has become a major cause of the failure of titanium-based implants.…”