Impact of Acrylamide on Cellular Senescence Response and Cell Cycle Distribution via an In-vitro Study.

Exposure to certain environmental toxins has been shown to be associated with cellular senescence mainly through induction of oxidative stress and impact on cellular systems. Acrylamide (ACR) has raised worldwide concerns regarding the high risk of human dietary exposure to its hazardous effect. Although there is ample evidence about the carcinogenicity of ACR, limited studies have focused on its impact on cellular aging. The levels of ß-galactosidase (SA-ß-gal) activity, cell cycle distribution, and the expression of the senescence-associated gene and inflammatory markers were evaluated following exposure of embryonic fibroblast cells to ACR. A significant elevation in SA-ß-gal activity after exposure to different concentrations of ACR was accompanied by a considerably increased level of reactive oxygen species and lipid peroxidation. ACR-treated cells showed a noticeable decline in the total antioxidant capacity and thiol molecules. Moreover, the expression of cellular senescence-related genes including p38, p53, and p21 significantly upregulated at the high concentration of 5 mM ACR. ACR also induced G0/G1 phase arrest in embryonic fibroblast cells. The current study results revealed that exposure to ACR could enhance senescence response, contributing to increased oxidative stress and cellular damage.

Effects of French maritime pine bark extract (Oligopin®) supplementation on bone remodeling markers in postmenopausal osteopenic women: A randomized clinical trial.

French maritime pine bark extract (FMPBE; Oligopin®), a dietary supplement, is rich in procyanidin. The objective of this study was to determine the effects of FMPBE on bone remodeling in postmenopausal osteopenic women. This randomized, double-blinded, placebo-controlled clinical trial was conducted on 40 postmenopausal osteopenic women. Individuals were randomly assigned to either FMPBE (250 mg/day, n = 21) or placebo (250-mg starch/day, n = 19) for 12 weeks. Biochemical indices, including bone remodeling marker, were assessed before and after the intervention. After the 12-week intervention, that is, FMPBE supplementation, a significant increase in bone alkaline phosphatase (BAP), procollagen type 1 amino-terminal propeptide (P1NP) levels and a significant decrease in C-terminal telopeptide of type I collagen (CTx1) were observed. Compared with the control group, FMPBE supplementation resulted in a significant increase in P1NP (0.015), BAP levels (0.001), and BAP/CTx1 ratio (p = 0.001) and a significant decrease in CTx1 levels (0.006). FMPBE supplementation for 12 weeks in postmenopausal osteopenic women produced favorable effects on bone markers. Meanwhile, further research is needed to determine whether FMPBE supplements can be used as a preventive strategy for bone loss in postmenopausal osteopenic women.

Molecular and biochemical evidence on the protective role of ellagic acid and silybin against oxidative stress-induced cellular aging.

Aging is a natural process in living organisms that is defined by some molecular and cellular changes with time. Various causes such as mitochondrial DNA aberrations, aggregation of proteins, telomere shortening, and oxidative stress have an influential role in aging of the cells. Natural antioxidants are compounds that are potent to protect the body from detrimental effects of molecules such as free radicals. The aim of this study was to evaluate the anti-aging properties of ellagic acid (EA) and silybin (SIL), as natural antioxidant compounds on rat embryonic fibroblast (REF) cells. These cells were pre-incubated with EA and SIL, thereafter were exposed to hydrogen peroxide (H2O2). Then, the cell viability, SA-ß-GAL activity, distribution of cell cycle, NF-κB, and mitochondrial complex I, II/IV enzyme activity were measured. The results of this study revealed the protective effects of EA and SIL in H2O2-treated REF cells, which confirm the previous achieved data on antioxidant and anti-inflammatory characteristics of EA and SIL against H2O2 in the treated REF cells. However, more new in vivo experiments are required to discover the anti-aging effects and mechanism of action of such compounds.

Protective effects of cerium oxide and yttrium oxide nanoparticles on reduction of oxidative stress induced by sub-acute exposure to diazinon in the rat pancreas.

Diazinon is a kind of organophosphorus (OP) compound that is broadly used against different species of insects and pests. Oxidative stress can occur at very early stages of diazinon exposure and the pancreas is one of the main target organs for toxicity by diazinon. The aim of this study was to evaluate the protective effects of cerium oxide nanoparticles (CeO2 NPs) and yttrium oxide nanoparticles (Y2O3 NPs) against the pancreatic damage from sub-acute exposure of diazinon. Diazinon at a dose of 70mg/kg/day was given through gavage to rats once a day. Along with diazinon, trace amounts of CeO2 NPs and Y2O3 NPs (35mg/kg and 45mg/kg per day, respectively) were administered by intraperitoneal injection once a day for 2 weeks. Animals weight and blood glucose were measured during the treatment, and oxidative stress biomarkers, diabetes physiology, function and viability of cells were investigated at the end of the treatment in serum and pancreas tissues. Apoptosis of islets was examined by the flow cytometry. The high blood glucose level and significant weight loss resulting from diazinon were modified as a result of the application of the NPs. A significant recovery in oxidative stress markers, pro-insulin, insulin, C-peptide, adenosine diphosphate/adenosine triphosphate (ATP/ADP) ratio, caspase-3 and -9 activities and apoptosis-necrosis in the islets was observed. In conclusion, administration of CeO2 NPs or Y2O3 NPs only or their combination with suitable and defined dose will help to overcome the consequences from oxidant agents.

Targeting the TLR4 signaling pathway by polyphenols: A novel therapeutic strategy for neuroinflammation.

A wide array of cell signaling mediators and their interactions play vital roles in neuroinflammation associated with ischemia, brain trauma, developmental disorders and age-related neurodegeneration. Along with neurons, microglia and astrocytes are also affected by the inflammatory cascade by releasing pro-inflammatory cytokines, chemokines and reactive oxygen species. The release of pro-inflammatory mediators in response to neural dysfunction may be helpful, neutral or even deleterious to normal cellular survival. Moreover, the important role of NF-κB factors in the central nervous system (CNS) through toll-like receptor (TLR) activation has been well established. This review demonstrates recent findings regarding therapeutic aspects of polyphenolic compounds for the treatment of neuroinflammation, with the aim of regulating TLR4. Polyphenols including flavonoids, phenolic acids, phenolic alcohols, stilbenes and lignans, can target TLR4 signaling pathways in multiple ways. Toll interacting protein expression could be modulated by epigallocatechin-3-gallate. Resveratrol may also exert neuroprotective effects via the TLR4/NF-κB/STAT signaling cascade. Its role in activation of cascade via interfering with TLR4 oligomerization upon receptor stimulation has also been reported. Curcumin, another polyphenol, can suppress overexpression of inflammatory mediators via inhibiting the TLR4-MAPK/NF-κB pathway. It can also reduce neuronal apoptosis via a mechanism concerning the TLR4/MyD88/NF-κB signaling pathway in microglia/macrophages. Despite a symphony of in vivo and in vitro studies, many molecular and pharmacological aspects of neuroinflammation remain unclear. It is proposed that natural compounds targeting TLR4 may serve as important pharmacophores for the development of potent drugs for the treatment of neurological disorders.

Functional Improvement in Rats' Pancreatic Islets Using Magnesium Oxide Nanoparticles Through Antiapoptotic and Antioxidant Pathways.

According to undiscovered toxicity and safety of magnesium oxide nanoparticles (MgO NPs) in isolated pancreatic islet cells, this study was designed to examine the effects of its various concentrations on a time-course basis on the oxidative stress, viability, and function of isolated islets of rat's pancreas. Pancreatic islets were isolated and exposed to different MgO NP (<100 nm) concentrations within three different time points. After that, oxidative stress biomarkers were investigated and the best exposure time was selected. Then, safety of MgO NPs was investigated by flow cytometry and fluorescent staining, and levels of insulin secretion and caspase activity were measured. The results illustrated a considerable decrease in oxidative stress markers such as reactive oxygen species (ROS) and lipid peroxidation (LPO) levels of pancreatic islets which were treated by MgO NPs for 24 h. Also, in that time of exposure, cell apoptosis investigation by flow cytometry and insulin test showed that MgO NPs, in a concentration of 100 µg/ml, decreased the rate of apoptotic cells via inhibiting caspase-9 activity and made a significant increase in the level of insulin secretion. Data of function and apoptosis biomarkers correlated with each other. It is concluded that the use of MgO NPs in concentration of as low as 100 µg/ml can induce antiapoptotic, antioxidative, and antidiabetic effects in rat pancreatic islets, which support its possible benefit in islet transplantation procedures.