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Styrene is an aromatic hydrocarbon compound present in the environment and have primary exposure through plastic industry. The current study was designed to evaluate styrene-induced toxicity parameters in rat plasma fasting blood glucose (FBG) level, oral glucose tolerance, insulin secretion, oxidative stress, and inflammatory cytokines in cellular and molecular levels. Styrene was dissolved in corn oil and administered at different doses (250, 500, 1000, 1500, 2000 mg/kg/day and control) to each rat, for 42 days. In treated groups, styrene significantly increased fasting blood glucose, plasma insulin (p < 0.001) and glucose tolerance. Glucose tolerance, insulin resistance and hyperglycemia were found to be the main consequences correlating gene expression of islet cells. Styrene caused a significant enhancement of oxidative stress markers (p < 0.001) and inflammatory cytokines in a dose and concentration-dependent manner in plasma (p < 0.001). Moreover, the activities of caspase-3 and −9 of the islet cells were significantly up-regulated by this compound at 1500 and 2000 mg/kg/day styrene administrated groups (p < 0.001). The relative fold change of GLUD1 was downregulated (p < 0.05) and upregulated at 1500 and 2000 mg/kg, respectively (p < 0.01). The relative fold changes of GLUT2 were down regulated at 250 and 1000 mg/kg and up regulated in 500, 1500 and 2000 mg/kg doses of styrene (p < 0.01). The expression level of GCK indicated a significant upregulation at 250 mg/kg and downregulation of relative fold changes in the remaining doses of styrene, except for no change at 2000 mg/kg of styrene for GCK. Targeting genes (GLUD1, GLUT2 and GCK) of the pancreatic islet cells in styrene exposed groups, disrupted gluconeogenesis, glycogenolysis pathways and insulin secretory functions. The present study illustrated that fasting blood glucose, insulin pathway, oxidative balance, inflammatory cytokines, cell viability and responsible genes of glucose metabolism are susceptible to styrene, which consequently lead to other abnormalities in various organs. [ABSTRACT FROM AUTHOR]

Objective(s): During type-1 diabetes treating by pancreatic islet transplantation, increasing oxidative stress and microbial contaminations are the main reasons of transplantation failure. In this study, we evaluated anti-apoptotic, antioxidant and antimicrobial potentials of phenolic compounds called ellagic acid (EA) and silybin on rat pancreatic islets. Materials and Methods: By doing MTT assay, effective concentrations of EA and silybin were determined as 1500 and 2100 μM, respectively. Then, ELISA methods, flow cytometry and MIC were done to investigate antioxidant, anti-apoptotic and antibacterial effects of those compounds, respectively. Results: Results of FITC Annexin-V and PI staining via flow cytometry, and also caspase-3 and -9 activities performed that EA has anti-apoptotic effects on pancreatic cells. Both compounds significantly diminished reactive oxygen species, and enhanced antioxidant power and insulin secretion. Furthermore, the minimum inhibitory concentration test indicated that these two have antibacterial effects on both Gram-positive and Gram-negative bacteria which usually contaminate the pancreatic islets. Conclusion: These findings support that use of EA and silybin can improve the function of islets which are used in transplantation, along with decreasing islets bacterial contamination. [ABSTRACT FROM AUTHOR]

Mercury (Hg) is a well-known heavy metal and causes various toxic effects. It is abundantly present in fish in the form of methyl mercury (MeHg). Also, various other forms of mercury can enter human body either from environment like inhalation or through dental amalgams. The present study was designed to assess MeHg induced toxicity in mouse plasma and pancreatic islets with respect to insulin secretion, oxidative balance, glucose tolerance, gene expression, caspases 3 and 9 activities. MeHg was dissolved in tap water and administered at doses 2.5, 5 and 10 mg/kg/day, for 4 weeks. In mice, MeHg significantly caused increase in plasma insulin as well as C-peptides. Glucose intolerance, insulin resistance and hyperglycemia are main consequences of our study that correlate with the gene expression changes of glucose homeostasis as well. MeHg caused increase lipid peroxidation in a dose-dependent manner in plasma as well as pancreatic islets. In addition, total thiol molecules and ferrous reducing antioxidant power in MeHg treated group was decreased in plasma as well as pancreatic islets. Caspases 3 and 9 activities of pancreatic islets were upregulated in MeHg exposed animals. Reactive oxygen species were extremely high in pancreatic islets of MeHg treated groups. MeHg disrupted gluconeogenesis/glycogenolysis pathways and insulin secretory functions of islets by targeting GDH, GLUT2 and GCK genes of pancreatic islets. In conclusion, the current study revealed that insulin pathways, oxidative balance and glucose metabolism encoded genetic makeup are susceptible to MeHg toxicity and the subsequent oxidative stress and alternations in gene expression could lead toward functional abnormalities in other organs. [ABSTRACT FROM AUTHOR]

Despite advances in sepsis management, it remains a major intensive-care-unit (ICU) concern. From new prospective, positive effects of metformin, such as anti-oxidant and anti-inflammatory properties are considered potentially beneficial properties for management of septic patients. This article reviewed the potential ameliorative effects of metformin in sepsis-induced organ failure. Information were retrieved from PubMed, Scopus, Embase, and Google Scholar. Multi-organ damage, oxidative stress, inflammatory cytokine stimulation, and altered circulation are hallmarks of sepsis. Metformin exerts its effect via adenosine monophosphate-activated protein kinase (AMPK) activation. It improves sepsis-induced organ failure by inhibiting the production of reactive oxygen species (ROS) and pro-inflammatory cytokines, preventing the activation of transcription factors related to inflammation, decreasing neutrophil accumulation/infiltration, and also maintaining mitochondrial membrane potential. Studies reported the safety of metformin therapeutic doses, with no evidence of lactic acidosis, in septic patients. [ABSTRACT FROM AUTHOR]

Salient evidence testifies the link between organophosphorus (OPs) exposure and the formation of free radical oxidants; and it is well accepted that free radicals are one of the basic concerns of senescence. To show the oxidative features of phosalone (PLN) as a key member of OPs, to induce senescence in rat embryonic fibroblast (REF) cells and to demonstrate the beneficial effects of the known antioxidant ellagic acid (EA) in diminishing the PLN-induced toxic effects, the levels of cell viability, oxidative stress markers, inflammatory cytokines, telomerase activity, and the expression of the genes related to senescence were investigated. Our results lend support to the hypothesis that PLN enhances the entire premature senescence parameters of REF cells. This accounts for the mechanistic approval of the role of OPs in induction of senescence in rat fibroblasts. Moreover, incorporation of EA diminished PLN toxicity mainly through suppression of p38 and p53 at gene and protein levels, and tempered the inflammation factors (TNF-α, IL-1β, IL-6 and NF-κB), which further affected cell division. Analysis of cell cycle showed that the percentage of G0/G1 arrest, in REF cells treated by EA was elevated as compared to control and PLN treated cells. [ABSTRACT FROM AUTHOR]