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Journal of Cellular and Molecular... Sep 2021Excitotoxic events underlying ischaemic and traumatic brain injuries activate degenerative and protective pathways, particularly in the hippocampus. To understand...
Excitotoxic events underlying ischaemic and traumatic brain injuries activate degenerative and protective pathways, particularly in the hippocampus. To understand opposing pathways that determine the brain's response to excitotoxicity, we used hippocampal explants, thereby eliminating systemic variables during a precise protocol of excitatory stimulation. N-methyl-d-aspartate (NMDA) was applied for 20 min and total RNA isolated one and 24 h later for neurobiology-specific microarrays. Distinct groups of genes exhibited early vs. delayed induction, with 63 genes exclusively reduced 24-h post-insult. Egr-1 and NOR-1 displayed biphasic transcriptional modulation: early induction followed by delayed suppression. Opposing events of NMDA-induced genes linked to pathogenesis and cell survival constituted the early expression signature. Delayed degenerative indicators (up-regulated pathogenic genes, down-regulated pro-survival genes) and opposing compensatory responses (down-regulated pathogenic genes, up-regulated pro-survival genes) generated networks with temporal gene profiles mirroring coexpression network clustering. We then used the expression profiles to test whether NF-κB, a potent transcription factor implicated in both degenerative and protective pathways, is involved in the opposing responses. The NF-κB inhibitor MG-132 indeed altered NMDA-mediated transcriptional changes, revealing components of opposing expression signatures that converge on the single response element. Overall, this study identified counteracting avenues among the distinct responses to excitotoxicity, thereby suggesting multi-target treatment strategies and implications for predictive medicine.
Topics: Animals; Brain Injuries, Traumatic; Gene Expression Regulation; Hippocampus; N-Methylaspartate; NF-kappa B; Protective Agents; Rats; Rats, Sprague-Dawley
PubMed: 34414662
DOI: 10.1111/jcmm.16864 -
BioMed Research International 2018Silymarin (SM), a standardized extract derived from (L.) Gaertn, is primarily composed of flavonolignans, with silibinin (SB) as its major active constituent. The...
Silymarin (SM), a standardized extract derived from (L.) Gaertn, is primarily composed of flavonolignans, with silibinin (SB) as its major active constituent. The present study aimed to evaluate the antigenotoxic activities of SM and SB using the alkaline comet assay in whole blood cells and to assess their effects on the expression of genes associated with carcinogenesis and chemopreventive processes. Different concentrations of SM or SB (1.0, 2.5, 5.0, and 7.5 mg/ml) were used in combination with the DNA damage-inducing agent methyl methanesulfonate (MMS, 800 M) to evaluate their genoprotective potential. To investigate the role of SM and SB in modulating gene expression, we performed quantitative real-time PCR (qRT-PCR) analysis of five genes that are known to be involved in DNA damage, carcinogenesis, and/or chemopreventive mechanisms. Treatment with SM or SB was found to significantly reduce the genotoxicity of MMS, upregulate the expression of and , and downregulate the expression of and . We observed no significant changes in expression levels following treatment with SM or SB. In conclusion, both SM and SB exerted antigenotoxic activities and modulated the expression of genes related to cell protection against DNA damage.
Topics: Antioxidants; Blood Cells; Cells, Cultured; Cytoprotection; DNA Damage; Down-Regulation; Flavonoids; Gene Expression; Humans; Silybum marianum; Protective Agents; Silybin; Silymarin; Up-Regulation
PubMed: 30370304
DOI: 10.1155/2018/6056948 -
Antioxidants & Redox Signaling May 2019Peptide receptor radionuclide therapy (PRRT) is in clinical use today to treat metastatic neuroendocrine tumors. Infused, radiolabeled, somatostatin analog peptides... (Review)
Review
AIMS
Peptide receptor radionuclide therapy (PRRT) is in clinical use today to treat metastatic neuroendocrine tumors. Infused, radiolabeled, somatostatin analog peptides target tumors that are killed by irradiation damage. The peptides, however, are also retained in kidneys due to glomerular filtration, and the administered doses must be limited to avoid kidney damage. The human radical scavenger and antioxidant, α-microglobulin (A1M), has previously been shown to protect bystander tissue against irradiation damage and has pharmacokinetic and biodistribution properties similar to somatostatin analogs. In this study, we have investigated if A1M can be used as a renal protective agent in PRRT.
RESULTS
We describe nephroprotective effects of human recombinant A1M on the short- and long-term renal damage observed following lutetium 177 (Lu)-DOTATATE (150 MBq) exposure in BALB/c mice. After 1, 4, and 8 days (short term), Lu-DOTATATE injections resulted in increased formation of DNA double-strand breaks in the renal cortex, upregulated expression of apoptosis and stress response-related genes, and proteinuria (albumin in urine), all of which were significantly suppressed by coadministration of A1M (7 mg/kg). After 6, 12, and 24 weeks (long term), Lu-DOTATATE injections resulted in increased animal death, kidney lesions, glomerular loss, upregulation of stress genes, proteinuria, and plasma markers of reduced kidney function, all of which were suppressed by coadministration of A1M. Innovation and Conclusion: This study demonstrates that A1M effectively inhibits radiation-induced renal damage. The findings suggest that A1M may be used as a radioprotector during clinical PRRT, potentially facilitating improved tumor control and enabling more patients to receive treatment.
Topics: Alpha-Globulins; Animals; Antioxidants; Biomarkers; Gene Expression Profiling; Histones; Humans; Kidney; Mice; Models, Animal; Octreotide; Organometallic Compounds; Radiation-Protective Agents; Survival Rate; Time Factors
PubMed: 29943622
DOI: 10.1089/ars.2018.7517 -
Acta Bio-medica : Atenei Parmensis Dec 2019Honey and its polyphenolic compounds are of main natural antioxidants that have been used in traditional medicine. The aim of this review was to identify the protective... (Review)
Review
OBJECTIVE
Honey and its polyphenolic compounds are of main natural antioxidants that have been used in traditional medicine. The aim of this review was to identify the protective effects of honey and chrysin (a polyphenol available in honey) against the chemical and natural toxic agents.
METHOD
The scientific databases such as MEDLINE, PubMed, Scopus, Web of Science and Google Scholar were searched to identify studies on the antidotal effects of honey and chrysin against toxic agents.
RESULTS
This study found that honey had protective activity against toxic agents-induced organ damages by modulating oxidative stress, inflammation, and apoptosis pathways. However, clinical trial studies are needed to confirm the efficacy of honey and chrysin as antidote agents in human intoxication.
CONCLUSION
Honey and chrysin may be effective against toxic agents. (www.actabiomedica.it).
Topics: Antidotes; Drug-Related Side Effects and Adverse Reactions; Flavonoids; Honey; Humans; Polyphenols; Protective Agents
PubMed: 31910181
DOI: 10.23750/abm.v90i4.7534 -
Gut and Liver Mar 2020With the increasing use of nonsteroidal anti-inflammatory drugs (NSAIDs), the incidence of lower gastrointestinal (GI) complications is expected to increase. However,... (Review)
Review
With the increasing use of nonsteroidal anti-inflammatory drugs (NSAIDs), the incidence of lower gastrointestinal (GI) complications is expected to increase. However, unlike upper GI complications, the burden, pathogenesis, prevention and treatment of NSAID-associated lower GI complications remain unclear. To date, no cost-effective and safe protective agent has been developed that can completely prevent or treat NSAID-related lower GI injuries. Selective COX-2 inhibitors, misoprostol, intestinal microbiota modulation, and some mucoprotective agents have been reported to show protective effects on NSAID-induced lower GI injuries. This review aims to provide an overview of the current evidence on the prevention of NSAID-related lower GI injuries.
Topics: Anti-Inflammatory Agents, Non-Steroidal; Cyclooxygenase 2 Inhibitors; Gastrointestinal Diseases; Humans; Lower Gastrointestinal Tract; Misoprostol; Protective Agents
PubMed: 31547642
DOI: 10.5009/gnl19201 -
Nutrients Jul 2021Cyclophosphamide (CP)-which is used to treat autoimmune diseases and cancer-is related to gonadotoxicity attributed to oxidative stress. As phycobiliproteins (PBPs) are...
Cyclophosphamide (CP)-which is used to treat autoimmune diseases and cancer-is related to gonadotoxicity attributed to oxidative stress. As phycobiliproteins (PBPs) are strong antioxidants that are unexplored as protective agents against male gonadotoxicity, our work aimed to investigate the effects of PBP crude extract on testicular damage and sperm parameter alterations caused by CP in mice. Three doses of PBP (50, 100, and 200 mg/kg) were tested in the experimental groups ( = 8 per group), administered concomitantly with 100 mg/kg CP. After 42 days receiving PBP daily and CP weekly, body and relative testicular weights, serum testosterone levels, testicular lipoperoxidation and antioxidant enzyme activity levels, and testicular histology and sperm parameter alterations were assessed. The results showed that PBP crude extract at 200 mg/kg prevented testosterone serum reduction, body weight loss, lipoperoxidation and enzyme activity increments, and sperm parameter alterations and partially ameliorated relative testicular weight reductions and histological damage in CP-treated mice. In conclusion, we showed that PBP crude extract (200 mg/kg) mitigated oxidative damage in the testes and ameliorated alterations in sperm parameters in mice treated with CP (100 mg/kg); therefore, PBP extract could be considered as a potential protective agent against CP toxicity.
Topics: Animals; Antioxidants; Body Weight; Cyclophosphamide; Disease Models, Animal; Male; Mice; Oxidative Stress; Phycobiliproteins; Protective Agents; Seminiferous Tubules; Spermatozoa; Testis; Testosterone
PubMed: 34444776
DOI: 10.3390/nu13082616 -
Journal of Natural Products Oct 2019Three new tetrahydrobenzocyclooctabenzofuranone lignan glucosides, longipedunculatins A-C (-), a new dibenzocyclooctadiene lignan glucoside, longipedunculatin D (), a...
Three new tetrahydrobenzocyclooctabenzofuranone lignan glucosides, longipedunculatins A-C (-), a new dibenzocyclooctadiene lignan glucoside, longipedunculatin D (), a new dibenzocyclooctadiene lignan (), five new tetrahydrobenzocyclooctabenzofuranone lignans (-), and two new simple lignans (, ) were isolated from the roots of Their structures and absolute configurations were established using a combination of MS, NMR, and experimental and calculated electronic circular dichroism data. Compound showed moderate hepatoprotective activity against -acetyl--aminophenol-induced toxicity in HepG2 cells with a cell survival rate at 10 μM of 50.8%. Compounds , , and showed significant in vitro inhibitory effects with an inhibition rate of 55.1%, 74.9%, and 89.8% on nitric oxide production assays at 10 μM.
Topics: Circular Dichroism; Cyclooctanes; Hep G2 Cells; Humans; Kadsura; Lignans; Liver; Magnetic Resonance Spectroscopy; Nitric Oxide; Plant Roots; Protective Agents
PubMed: 31556297
DOI: 10.1021/acs.jnatprod.9b00576 -
Environmental Science and Pollution... Oct 2022Ochratoxin A (OTA) is one of the most dangerous and that pollute agricultural products, inducing a variety of toxic effects in humans and animals. The current study...
Aspergillus awamori attenuates ochratoxin A-induced renal and cardiac injuries in rabbits by activating the Nrf2/HO-1 signaling pathway and downregulating IL1β, TNFα, and iNOS gene expressions.
Ochratoxin A (OTA) is one of the most dangerous and that pollute agricultural products, inducing a variety of toxic effects in humans and animals. The current study explored the protective effect of different concentrations of Aspergillus awamori (A. awamori) against OTA (0.3 mg/kg diet) induced renal and cardiac damage by exploring its mechanism of action in 60 New Zealand white male rabbits. Dietary supplementation of A. awamori at the selected doses of 50, 100, and 150 mg/kg diet, respectively, for 2 months significantly improved the rabbit's growth performance; modulated the suppressed immune response and restored the altered hematological parameters; reduced the elevated levels of renal injury biomarkers such as urea, creatinine, and alkaline phosphatase; and increased serum total proteins concentrations. Moreover, it also declined enzymatic activities of cardiac injury biomarkers, including AST, LDH, and CK-MB. A. awamori alleviated OTA-induced degenerative and necrotic changes in the kidney and heart of rabbits. Interestingly, A. awamori upregulated Nrf2/OH-1 signaling pathway. Therefore enhanced TAC, CAT, and SOD enzyme activities and reduced OTA-induced oxidative and nitrosative stress by declining iNOS gene expression and consequently lowered MDA and NO levels. In addition to attenuating renal and cardiac inflammation via reducing IL-1β, TNF-α gene expressions in a dose-dependent response. In conclusion,this is the first report to pinpoint that dietary incorporation of A. awamori counteracted OTA-induced renal and cardiac damage by potentiating the rabbit's antioxidant defense system through its potent antioxidant, free radical scavenging, and anti-inflammatory properties in a dose-dependent response. Based on our observations, A. awamori could be utilized as a natural protective agent against ochratoxicosis in rabbits.
Topics: Animals; Male; Rabbits; Alkaline Phosphatase; Antioxidants; Aspergillus; Biomarkers; Creatinine; Free Radicals; Gene Expression; Kidney; NF-E2-Related Factor 2; Ochratoxins; Oxidative Stress; Protective Agents; Signal Transduction; Superoxide Dismutase; Tumor Necrosis Factor-alpha; Urea
PubMed: 35576029
DOI: 10.1007/s11356-022-20599-y -
Prostaglandins, Leukotrienes, and... Jan 20151-acetyl,2-docosahexaenoyl-glycerophosphocholine (AceDoPC) has been made to prevent docosahexaenoyl (DHA) to move to the sn-1 position as it rapidly does when present in... (Review)
Review
1-acetyl,2-docosahexaenoyl-glycerophosphocholine (AceDoPC) has been made to prevent docosahexaenoyl (DHA) to move to the sn-1 position as it rapidly does when present in 1-lyso,2-docosahexaenoyl-GPC (lysoPC-DHA), an efficient DHA transporter to the brain. When incubated with human blood, AceDoPC behaves closer to lysoPC-DHA than PC-DHA in terms of binding to plasma albumin and lipoproteins, and DHA incorporation into platelets and red cells. In addition, AceDoPC prevents more efficiently the deleterious effects of the experimental stroke in rats than does unesterified DHA. Also, AceDoPC inhibits platelet-activating factor-induced human blood platelet aggregation. Overall, AceDoPC might act as an efficient DHA transporter to the brain, and as a neuro-protective agent by itself.
Topics: Animals; Brain; Humans; Neuroprotective Agents; Phosphatidylcholines; Phospholipids; Stroke
PubMed: 24582148
DOI: 10.1016/j.plefa.2014.01.005 -
Nutricion Hospitalaria Sep 2014Phospholipids are amphipathic lipids, which are found in all the cell membranes, organized as a lipid bilayer. They belong to the glycerol-derived lipids, showing a... (Review)
Review
Phospholipids are amphipathic lipids, which are found in all the cell membranes, organized as a lipid bilayer. They belong to the glycerol-derived lipids, showing a similar structure as triglycerides. The current interest of them comes from its effectiveness to incorporate different fatty acids in the cell membrane, as they exhibit better absorption and utilization than triglycerides. In this paper, the bibliographical data published about the benefits of the phospholipids in inflammatory processes, cancer, cardiovascular diseases, neurological disorders, liver disease and as an antioxidants transporter is reviewed.
Topics: Animals; Anti-Inflammatory Agents; Anticarcinogenic Agents; Antioxidants; Drug Industry; Humans; Phospholipids; Protective Agents
PubMed: 25561100
DOI: 10.3305/nh.2015.31.1.7961