ABSTRACT
AIMS: 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 (ß) cell toxicity via HMGB1/TLR2/TLR4/MAPK/NF-ÒB signaling pathway. MAIN METHODS: Human pancreatic ß cell (1.1B4) was used in the present study. Four experimental groups were created as control, melatonin (10⯵M), doxorubicin (2⯵M) 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. KEY FINDINGS: 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 destroyed F-actin distribution and elevated TLR2 and some apoptotic proteins, including Bax. However, co-treatment of melatonin with doxorubicin could reverse depolarization of MMP and inhibition of apoptosis through MAPK/NF-кB signaling by decreasing TOS and increasing TAS. The co-treatment reversed the alternations of TLR2, TLR4, MAPKs and apoptotic protein expressions induced by doxorubicin. SIGNIFICANCE: Melatonin could be a good candidate against pancreatic ß cell toxicity-induced by doxorubicin through TLR2/TLR4/MAPK/NF-кB pathways.
Subject(s)
Doxorubicin/adverse effects , Insulin-Secreting Cells/drug effects , Melatonin/pharmacology , Protective Agents/pharmacology , Toll-Like Receptor 2/metabolism , Toll-Like Receptor 4/metabolism , Antibiotics, Antineoplastic/adverse effects , Antioxidants/pharmacology , Apoptosis/drug effects , Cells, Cultured , HMGB1 Protein/metabolism , Humans , Insulin-Secreting Cells/metabolism , Insulin-Secreting Cells/pathology , Membrane Potential, Mitochondrial/drug effects , NF-kappa B/metabolism , Oxidants/metabolism , Oxidative Stress/drug effects , Signal Transduction/drug effects , Toll-Like Receptor 2/genetics , Toll-Like Receptor 4/genetics , p38 Mitogen-Activated Protein Kinases/metabolismABSTRACT
OBJECTIVES: To investigate the prevalence and impacts of heavy menstrual bleeding (HMB) on anemia, fatigue, and the quality of life (QoL) in women of reproductive age. METHODS: This study was conducted among 306 women of reproductive age who presented at the internal medicine outpatient departments of the training and research hospital of a university. The data of the study were collected by the "Data collection form", "SF-36 Quality of Life Scale (SF-36 QoLS)" and "Brief Fatigue Inventory (BFI)". RESULTS: The prevalence of HMB in women of reproductive age was 37.9%. The ferritin level and physical functions were found to decrease significantly as the duration of menstruation increased (p<0.05). Besides, a positive but very weak relationship was found between the menstruation duration and the subdimensions of the global BFI and the general health perception subscale of the SF-36 QoLS (p<0.05). CONCLUSION: It was determined that HMB is common and has negative effects on anemia, fatigue and some subdimensions of the QoL. Regular screening for HMB that may not be expressed by many women may therefore be useful in preventing and resolving the health problems that it will cause.
