The role of toll-like receptors in the protective effect of melatonin against doxorubicin-induced pancreatic beta cell toxicity
Abstract
Doxorubicin, an anticancer drug, has a toxic effect on many tissues such as heart, pancreas, liver, kidney, and testis. The aim of current study is to investigate whether melatonin would be protective in doxorubicin-induced beta (β) cell toxicity via HMGB1/TLR2/TLR4/MAPK/NF-қB signaling pathway. Human pancreatic β cell (1.1B4) was used in the present study. Four experimental groups were created as control, melatonin (10 μM), doxorubicin (2 μM) and the combination of melatonin with doxorubicin. Following 24-h treatment, Mitogen-activated protein kinase (MAPKs), Toll like receptors (TLRs) including TLR2 and TLR4, pro-and anti-apoptotic protein expression levels were determined by western blotting. Total antioxidant (TAS), oxidant status (TOS) and oxidative stress index (OSI) of the cells as well as superoxide dismutase (SOD) levels were determined. Active caspase-8 activity was measured and TUNEL staining was performed to study apoptotic pathways. Mitochondrial membrane potential (MMP), some protein expressions and F-actin distribution were analyzed. Doxorubicin caused to depolarize MMP, resulting in enhancing apoptosis by activation of caspase-8 via MAPKs/NF-кB pathway via elevation of TOS and decreasing TAS. Also, doxorubicin d...Continue Reading
References
Melatonin attenuated brain death tissue extract-induced cardiac damage by suppressing DAMP signaling
Toll-like receptor 2 and Toll-like receptor 4 predict favorable prognosis in local pancreatic cancer
Citations
Related Concepts
Related Feeds
Apoptosis
Apoptosis is a specific process that leads to programmed cell death through the activation of an evolutionary conserved intracellular pathway leading to pathognomic cellular changes distinct from cellular necrosis