Molecular evidence on the protective effect of ellagic acid on phosalone-induced senescence in rat embryonic fibroblast cells

Abstract

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.

RETRACTED ARTICLE: Neuroprotective effects of ellagic acid on cuprizone-induced acute demyelination through limitation of microgliosis, adjustment of CXCL12/IL-17/IL-11 axis and restriction of mature oligodendrocytes apoptosis

“… 2012 ; Baeeri et al. 2017 ). When EA is used orally, it undergoes specific metabolism by the gut microbiota and converts to urolithins that are much better absorbed in the gastrointestinal track.…”

Manipulation of molecular pathways and senescence hallmarks by natural compounds in fibroblast cells

“…8 The caspases activities were depicted as the percentage of controls that was considered 100%. Both caspase-3 and -9 have substrate selectivity for the peptide sequences of Ac-DEVD-and Ac-LEHD-specific caspaserecognition sequence, which have been labeled with qNA (chromophore r-nitroaniline), respectively.…”

“…8 Finally, the percentage of fluorescence cells at G1, S, and G2 phases was measured by a flow cytometer. The NIH3T3 cells were treated with EA and S. flavida (as the most effective plant extract, selected based on the results mentioned in sections 4.1-4.5).…”

“…[6][7][8] In spite of the multifaceted features of senescence, stable growth arrest has been suggested to halt the progression of senescence, predominantly through two tumor suppressor pathways: p53/p21 and p16INK4a INK4a /Rb (retinoblastoma), the key regulators of senescence events whose quantification possibly will define the senescence state. For instance, elevated SA-β-Gal contributes to the phonotypical features of senescence cells and is a typical marker used to discriminate senescence.…”

Differences in Inflammation, Apoptosis and Tissue Hypo-perfusion Indicators Caused by Using Two Different Gauges in Cecal Ligation and Puncture-induced Rat Models of Sepsis

“…PCR was carried out under the following conditions: 30 s at 95 °C for 1 cycle, 40 cycles of 95 °C for 5 s, 60 °C for 34 s and 72 °C for 45 s. One cycle of 30 s 72 °C was done nally to allow nal extension(23). The sequences of primers used for qRT-PCR are presented below; For Glyceraldehyde-3-phosphate dehydrogenase (gene symbol: GAPDH) sense primer (5′-AGTCTACTGGCGTCTTCACC -3′) antisense primer (5′-CCACGATGCCAAAGTTGTCA -3′) For AMP-activated catalytic subunit alpha 1 (AMPK) (gene symbol: Prkaa1) sense primer (5′-CCGTCTTATAGTTCAACCAT-3′) antisense primer (5′-TTCGTTCATTATTCTCCTGTT-3′) For Microtubule-associated protein 1 light chain 3 beta (LC3IIb) (gene symbol: Map1lc3b) sense primer (5′-CAGTGATTATAGAGCGATACA-3′) antisense primer (5′-GCCTTCTAATTATCTTGATGAG -3′) Blood samples parameters Whole blood assessment…”