Microglia (MG) are resident phagocytes in the brain responsible for neuronal maintenance. The regulation of MG necroptosis is required for protecting neurons during neurodegenerative diseases. ...Therefore, this study proposed to elucidate the molecular mechanisms underlying microglia necroptosis during long-time apoptotic stimuli (lipopolysaccharide, LPS). The protective role of plasmalogens (PLS) was also investigated against LPS insult in MG cells (including BV2 and MG6 cell lines). LPS produced time-dependent decreases in the survival of BV2 and MG6 cells mediated by the caspase signaling pathway. Interestingly, MG death was mediated by caspase-8 and 9 signaling pathways suggesting that MG necroptosis was actively attributed to long-time LPS treatment through intrinsic and extrinsic pathways. Notably, caspase signaling was markedly inhibited in the PLS-pretreated cells; thereby, PLS were capable of maintaining the MG cell population and inhibit the MG necroptosis against the longtime of LPS administration via its antioxidant and anti-inflammatory properties.
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Aflatoxin B1 (AFB1) is a common environmental pollutant that poses a major hazard to both humans and animals. Acacia senegal (Gum) is well-known for having antioxidant and anti-inflammatory bioactive ...compounds. Our study aimed to scout the nephroprotective effects of Acacia gum (Gum) against AFB1-induced renal damage. Four groups of rats were designed: Control, Gum (7.5 mg/kg), AFB1 (200 µg/kg b.w) and AFB1-Gum, rats were co-treated with both Gum and AFB1. Gas chromatography-mass spectrometry (GC/MS) analysis was done to determine the phytochemical constituents in Gum. AFB1 triggered profound alterations in kidney function parameters (urea, creatinine, uric acid, and alkaline phosphatase) and renal histological architecture. Additionally, AFB1 exposure evoked up-regulation of mRNA expression levels of inflammatory cytokines, including interleukin-6 (IL-6), tumor necrosis factor α (TNFα), inducible nitric oxide synthase (iNOS), and nuclear factor kB p65 (NF-κB/P65) in renal tissue. The oxidative distress and apoptotic cascade are also instigated by AFB1 intoxication as depicted in down-regulated protein expression of the nuclear factor erythroid 2–related factor 2 (Nrf2) and superoxide dismutase type 1 (SOD1) along with upregulation of cytochrome c (Cyto c), and cleaved Caspase3 (Casp3–17 and 19) in renal tissue. In conclusion, current study obviously confirms the alleviating effects of Gum supplementation against AFB1-induced renal dysfunction, oxidative harm, inflammation, and cell death. These mitigating effects are suggested to be attributed to Gum's antioxidant and anti-inflammatory activities. Our results recommend Gum supplementation as add-on agents to food that might aid in protection from AFB1-induced nephrotoxicity.
•Aflatoxin B1- provoked renal damage via oxidative stress and inflammatory pathways.•Acacia senegal (Gum) ameliorates AFB1-induced renal damage.•Gum inhibits oxidative stress and inflammation in the AFB1-induced renal damage.•Gum reduces AFB1-induced apoptosis in rats’ kidney.•Gum supplementation has therapeutic potential against AFB1-induced renal damage.
N-nitrosodiethylamine (ND) is an extremely toxic unavoidable environmental contaminant. CopperII-albumin (CuAB) complex, a newly developed Cu complex, showed antioxidant and anti-inflammatory ...potential. Hereby, we explored the plausible neuroprotective role of CuAB complex toward ND-evoked neurotoxicity in mice. Twenty-four male mice were sorted into 4 groups (6 mice each). Control group, mice were administered oral distilled water; and CuAB group, mice received CuAB complex at a dose of 817 µg/kg orally, three times weekly. In ND group, ND was given intraperitoneally (50 mg/kg body weight, once weekly for 6 w). CuAB+ND group, mice were administered a combination of CuAB and ND. The brain was quickly extracted upon completion of the experimental protocol for the evaluation of the oxidative/antioxidative markers, inflammatory cytokines, and histopathological examination. Oxidative stress was induced after ND exposure indicated by a reduction in GSH and SOD1 level, with increased MDA level. In addition, decreased expression of SOD1 proteins, Nrf2, and 5-HT mRNA expression levels were noticed. An apoptotic cascade has also been elicited, evidenced by overexpression of Cyt c, Cl. Casp 3. In addition, increased regulation of proinflammatory genes (TNF-α, IL-6, iNOS, Casp1, and NF-κB (p65/p50); besides, increment of protein expression of P-IKBα and reduced expression of IKBα. Pretreatment with CuAB complex significantly ameliorated ND neuronal damage. Our results recommend CuAB complex supplementation because it exerts neuroprotective effects against ND-induced toxicity.
N-myc downstream-regulated gene 2 (NDRG2) as a tumor suppressor is frequently downregulated in human T-lymphotropic retrovirus (HTLV-1)-infected adult T-cell leukemia (ATL) and variety of cancers, ...and negatively regulates PI3K signaling pathways through dephosphorylation of PTEN with protein phosphatase 2A (PP2A). We recently identified that protein arginine methyltransferase 5 (PRMT5) is one of novel NDRG2 binding proteins and the knockdown of PRMT5 induces cell apoptosis with degradation of several signaling molecules. To investigate how the apoptosis is induced by the knockdown PRMT5 expression, heat shock protein 90 alpha (HSP90A) was identified as a binding protein for NDRG2 or PRMT5 by immunoprecipitation-mass analysis. NDRG2/PP2A complex inhibited arginine methyltransferase activity of PRMT5 through dephosphorylation at Serine 335 (S335); however, in NDRG2low ATL-related cells, highly phosphorylated PRMT5 at S335 was mainly localized in cytoplasm with binding to HSP90A, resulting in enhancing arginine-methylation at the middle domain (R345 and R386). Since knockdown of PRMT5 expression or forced expression of HSP90A with alanine replacement of R345 or R386 induced apoptosis with the degradation of client proteins in NDRG2low ATL-related and other cancer cells, we here identified that the novel arginine methylations of HSP90A are essential for maintenance of its function in NDRG2low ATL and other cancer cells.
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•A PRMT5-MEP50 complex is a novel NDRG2 binding partner.•Cytoplasmic PRMT5 plays a crucial role in the growth of NDRG2low ATL cells.•High phosphorylation of PRMT5 S335 maintains its activity in NDRG2low ATL cells.•Novel arginine methylation HSP90A by PRMT5 is essential for survival of ATL and other cancers.
Aflatoxin B1 (AF) is an unavoidable environmental pollutant that contaminates food, feed, and grains, which seriously threatens human and animal health. Arabic gum (AG) has recently evoked much ...attention owing to its promising therapeutic potential. Thus, the current study was conducted to look into the possible mechanisms beyond the ameliorative activity of AG against AF-inflicted hepatic injury. Male Wistar rats were assigned into four groups: Control, AG (7.5 g/kg b.w/day, orally), AF (200 µg/kg b.w), and AG plus AF group. AF induced marked liver damage expounded by considerable changes in biochemical profile and histological architecture. The oxidative stress stimulated by AF boosted the production of plasma malondialdehyde (MDA) level along with decreases in the total antioxidant capacity (TAC) level and glutathione peroxidase (GPx) activity. Additionally, AF exposure was associated with down-regulation of the nuclear factor erythroid2–related factor2 (Nrf2) and superoxide dismutase1 (SOD1) protein expression in liver tissue. Apoptotic cascade has also been evoked following AF-exposure, as depicted in overexpression of cytochrome c (Cyto c), cleaved Caspase3 (Cl. Casp3), along with enhanced up-regulation of inflammatory mediators such as tumor necrosis factor-α (TNF-α), interleukin (IL)-6, inducible nitric oxide synthase (iNOS), and nuclear factor kappa-B transcription factor/p65 (NF-κB/p65) mRNA expression levels. Interestingly, the antioxidant and anti-inflammatory contents of AG may reverse the induced oxidative damage, inflammation, and apoptosis in AF-exposed animals.
Concurrent exposure to antimicrobial and nonsteroidal anti-inflammatory drugs (NSAIDs) is usually inevitable in most infections and postsurgery. Consequently, the present study was designed to assess ...the intertwining impact of coadministration of cefepime (CP, a wide spectrum antibiotic) and diclofenac sodium (DF, an NSAID) on rat's liver, kidney, and testes. Rats received saline, CP (180 mg/kg/day, IM), DF (10 mg/kg/day, IM), or a combination of CP and DF. After 14 days, CP or DF induced tissue damage expressed by marked biochemical alterations in hepatic and renal function tests. Besides this, disrupted lipid metabolism and testosterone levels along with significant histological changes in hepatic, renal, and testicular tissues were noticed. A significant increase in malondialdehyde and decreases in superoxide dismutase and catalase activities alongside significant upregulated caspase 3 expression in tissues following CP or DF treatment suggested a bearable influence of oxidative stress, lipid peroxidation, and cell death. Accordingly, the simultaneous therapy of CP and DF evoked more obvious tissue damage than their individual treatment. Overall, data concluded that concurrent use of CP and DF in medical practice is a worrisome matter, so it should be done cautiously to avoid synergistic deleterious outcomes.
Tramadol hydrochloride (TH) is an opioid centrally acting analgesic used to treat moderate to severe acute and chronic pains. Therefore, it became the most prescribed opioid worldwide.In this study, ...we investigated the neurodegenerative disorders of tramadol in brain tissues and the protective role of royal jelly. Twenty male albino rats allocated into four groups: Group 1,served as a control group, and Group 2, administrated with tramadol at a dose of 20 mg/kg/b. W for 60 days. Group 3: rats administrated with tramadol at a dose of 20 mg/kg/b. W for 60 days and treated with royal jelly (RJ) in a 100 mg/kg dose. b.w. Group 4: Rats inoculated with royal jelly (RJ) at a dose of 100 mg/kg. b.w. Blood samples were collected for hematological and biochemical analysis. Brain tissues were harvested for neurodegeneration biomarkers detection and histopathological examinations. Administration of tramadol revealed a significant decrease in Hb concentration, RBCs count, PCV %, Lymphocytes %, and platelets number, while WBCS count, Neutrophiles, and monocytes % increased. Also, Tramadol induced a decrease in glucose-6phosphate dehydrogenase (G6PD) while creatine kinase -BB (CK-BB) and neuron-specific enolase enzymes (NSE) were decreased.Tramadol increased the lipid peroxidation MDA, while total antioxidants capacity (TAC) and glutathione reductase (GSH) concentrations were decreased. Histopathologically, tramadol-induced neurodegenerative changes in brain neurons manifested by acute necrosed neurons with gliosis and vascular congestions. The administration of royal jelly improved the previous deleterious effects by decreasing brain tissue oxidative stress. Tramadol misuse caused neurodegenerative effects and was relieved by RJ administration.
The aminoglycoside Gentamicin is a commonly used antibiotic counteracting the Gram-ve microorganisms. Rats administered with Gentamicin showing a reduced testicular weight and inhibited ...spermatogenesis, as gentamicin generates ROS, decreasing the antioxidant reserve and accelerate mitochondrial dysfunction which then leads to apoptosis and testicular tissue destruction. This study was designed to investigate the protective effects of curcumin and/or quercetin on the gentamicin induced testicular damage or toxicity in sexually mature adult rats. Pre-treatment with curcumin and/or quercetin, markedly inhibited and ameliorated the reduction in sperm count, viability, motility and sperm production in gentamicin treated rats. Moreover, curcumin and/or quercetin, significantly reduce teratospermia including head or tail abnormalities that observed in the gentamicin treated rats. These abnormalities were effectively normalized by curcumin and/or quercetin pretreatment improving the testicular tissue via counteracting of ROS, improvement of spermatogenesis and ameliorate the sperms quality and quantity. In conclusion supplementation of curcumin and/or quercetin improving the sperm count and morphology via testicular cell repair, counteracting the undesirable effect of gentamicin.
Nitrosodiethylamine (NDEA) is a potent oxidant induces neurodegeneration via (reactive oxygen species) ROS. Copper is an important metal essential for scavenging free radicals, development of central ...nervous system (CNS) and redox angiogenesis signaling. Vascular endothelial growth factor (VEGF) is well known as efficacious and long-term signal that stimulates angiogenesis, where its expression is copper dependent. We examined the copper protective effect against brain vascular damage initiated by NDEA. NDEA induces brain vascular wall damage, necrosis with interstitial hemorrhage and diminishes VEGF expression. Histopathological examination showing a great improvement of brain tissue in copper treated mice with significant increase in VEGF expression. Higher levels of intracellular copper can stimulate angiogenesis and exhibited a significant protection against NDEA induced brain vascular damage, confirming its ability to enhance antioxidant activity and angiogenesis initiation. Our report presents first evidence that inducible VEGF expression in brain is sensitive to copper; moreover, copper-based therapeutics represents a novel approach to reduce brain vascular damage induced by NDEA generated ROS
Fascioliasis is a parasitic foodborne disease caused by the liver flukes,
and
. Such parasites cause serious illness in numerous domestic animals and also in humans. Following infection, the parasite ...secretes a variety of molecules that immediately interact with the host immunity to establish successful infection. These molecules include cathepsin L peptidase 1 (CatL1); the highly investigated diagnostic and vaccine antigens using various animal models. However, a few studies have analyzed the potentials of FhCatL1 as a diagnostic or vaccine antigen using bioinformatic tools and much less for FgCatL1. The present study provides inclusive and exclusive information on the physico-chemical, antigenic and immunogenic properties of
cathepsin L1 (FhCatL1) protein using multiple bioinformatic analysis tools and several online web servers. Also, the validation of our employed available online servers was conducted against a huge collection of previously published studies focusing on the properties of FhCatL1as a diagnostic and vaccine antigen.
For this purpose, the secondary, tertiary, and quaternary structure of FhCatL1 protein were also predicted and analyzed using the SWISS-MODEL server. Validation of the modeled structures was performed by Ramachandran plots. The antigenic epitopes of the protein were predicted by IEDB server.
Our findings revealed the low similarity of FhCatL1 with mammalian CatL1, lacking signal peptides or transmembrane domain, and the presence of 33 phosphorylation sites. Also, the containment of FhCatL1 for many topological, physico-chemical, immunological properties that favored its function of solubility and interaction with the immune components were reported. In addition, the earlier worldwide reports documented the high efficacy of FhCatL1 as a diagnostic and vaccine antigen in different animals. Altogether, FhCatL1 is considered an excellent candidate for using in commercialized diagnostic assays or vaccine products against fascioliasis in different animal species. Our assessment also included FgCatL1 and reported very similar findings and outputs to those of FhCatL1.
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