scholarly journals Modifications of expression of genes and proteins involved in DNA repair and nitric oxide metabolism by carbatonides [disodium-2,6-dimethyl-1,4-dihydropyridine- 3,5-bis(carbonyloxyacetate) derivatives] in intact and diabetic rats

2017 ◽  
Vol 68 (3) ◽  
pp. 212-227 ◽  
Author(s):  
Kristīne Ošiņa ◽  
Elina Leonova ◽  
Sergejs Isajevs ◽  
Larisa Baumane ◽  
Evita Rostoka ◽  
...  
Keyword(s):  
Gene Expression ◽  
Dna Repair ◽  
Diabetic Rats ◽  
Dna Breaks ◽  
Inos Gene ◽  
Expression Of Genes ◽  
Nitric Oxide Metabolism ◽  
Vis Spectroscopy ◽  
Type 1 Dm ◽  
Inos Gene Expression

Abstract Studies on the pathogenesis of diabetes mellitus complications indicate that the compounds reducing free radicals and enhancing DNA repair could be prospective as possible remedies. Carbatonides, the disodium-2,6-dimethyl-1,4- dihydropyridine-3,5-bis(carbonyloxyacetate) derivatives, were tested for these properties. EPR spectroscopy showed that metcarbatone was an effective scavenger of hydroxyl radicals produced in the Fenton reaction, etcarbatone, and propcarbatone were less effective, styrylcarbatone was ineffective. UV/VIS spectroscopy revealed that styrylcarbatone manifested a hyperchromic effect when interacting with DNA, while all other carbatonides showeda hypochromic effect. Rats with streptozotocin induced type 1 DM were treated with metcarbatone, etcarbatone or styrylcarbatone (all compounds at doses 0.05 mg kg-1 or 0.5 mg kg-1) nine days after the DM approval. Gene expression levels in kidneys and blood were evaluated by quantitative RT-PCR; protein expression - immunohistochemically in kidneys, heart, sciatic nerve, and eyes; DNA breakage - by comet assay in nucleated blood cells. Induction of DM induced DNA breaks; metcarbatone and styrylcarbatone (low dose) alleviated this effect. Metcarbatone and etcarbatone up-regulated mRNA and protein of eNOS in kidneys of diabetic animals; etcarbatone also in myocardium. Etcarbatone reduced the expression of increased iNOS protein in myocardium, nerve, and kidneys. iNos gene expression was up-regulated in kidneys by etcarbatone and metcarbatone in diabetic animals. In blood, development of DM increased iNos gene expression; etcarbatone and metcarbatone normalised it. Etcarbatone up-regulated the expression of H2AX in kidneys of diabetic animals but decreased the production of c-PARP1. Taken together, our data indicate that carbatonides might have a potential as drugs intended to treat DM complications.

scholarly journals Impacts of garlic extract on testicular oxidative stress and sperm characteristics in type 1 and 2 diabetic rats: An experimental study

2021 ◽  
pp. 929-942
Author(s):  
Fatemeh Lotf ◽  
Nasrin Ziamajidi ◽  
Roghayeh Abbasalipourkabir ◽  
Mohammad Taghi Goodarzi ◽  
Sara Soleimani Asl
Keyword(s):  
Oxidative Stress ◽  
Gene Expression ◽  
Sperm Quality ◽  
Diabetic Rats ◽  
Garlic Extract ◽  
Inos Gene ◽  
Total Antioxidant ◽  
Total Oxidative Status ◽  
Inos Gene Expression

Background: Hyperglycemia damages various tissues such as the testes through oxidative stress and inflammation, which can eventually lead to infertility. Objective: Garlic extract effects on the testicular tissue of diabetic rats were investigated. Materials and Methods: In this experimental study, 36 male Wistar rats (8-wk old, weighing 230-300 gr) were randomly divided into 6 groups (n = 6/each) including; C: control rats, G: received 0.4 gr of garlic extract/100 gr body weight, D1: Streptozotocin-induced-diabetic rats or type 1, D1+G: D1 rats that were treated with garlic, D2: Streptozotocin + nicotinamide-induced-diabetic rats or type 2, D2+G: D2 rats treated with garlic. At the end of the study, serum testosterone was assayed by ELISA. Also, sperm quality and quantity were evaluated. For determination of oxidative stress status, total antioxidant capacity, total oxidative status, lipid peroxidation, and thiol groups were assayed in the testis tissues of the rats by colorimetric methods. Also, inducible nitric oxide synthase (iNOS) gene expression and the protein level of interleukin-1-1β (IL-1β) were determined by quantitative real-time polymerase chain reaction and enzyme-linked immunosorbent assay, respectively. Results: In diabetic rats, glucose, total oxidative status and lipid peroxidation, iNOS gene expression, and IL-1β were higher than in non-diabetic rats, whereas testosterone, total antioxidant capacity and thiol groups, and sperm quality were significantly lower compared with control rats. These alterations were normalized by garlic intervention. Conclusion: In diabetic rats, garlic was associated with reduced glucose, oxidative stress, IL-1β, and iNOS gene expression and increased testosterone and sperm quality. So, the results suggest that garlic can reduce the severity of damage in testicular tissues of diabetic rats through its hypoglycemic, antioxidant, and anti-inflammatory properties. Key words: Diabetes mellitus, Garlic, Oxidative stress, Inflammation, Testis.

scholarly journals Anti-Inflammatory Effects of Abeliophyllum distichum Nakai (Cultivar Okhwang 1) Callus through Inhibition of PI3K/Akt, NF-κB, and MAPK Signaling Pathways in Lipopolysaccharide-Induced Macrophages

Processes ◽  
2021 ◽  
Vol 9 (6) ◽  
pp. 1071
Author(s):  
Tae-Won Jang ◽  
Jae-Ho Park
Keyword(s):  
Gene Expression ◽  
Polymerase Chain Reaction ◽  
Signaling Pathways ◽  
Chain Reaction ◽  
Inos Gene ◽  
Polymerase Chain ◽  
Cox 2 ◽  
Anti Inflammatory ◽  
Abeliophyllum Distichum ◽  
Inos Gene Expression

One of the Korean endemic plants, Abeliophyllum distichum Nakai (Oleaceae), contains acteoside, which is a glycoside exhibiting neuroprotective, anti-inflammation effects and antibacterial capacities. We conducted an investigation on the effects of the callus of A. distichum (cultivar Okhwang 1, CAO) on pro-inflammatory mediators released following nuclear factor-кB (NF-кB), phosphatidylinositol 3-kinase/Akt (PI3K-Akt) and mitogen-activated protein kinase (MAPK) signal activation in lipopolysaccharide (LPS)-induced RAW 264.7 cells. Immunoblotting was employed to find out the expression of cyclooxygenase-2 (COX-2), inducible nitric oxide (iNOS), and activation of MAPK molecules, NF-κB and Akt. Cytokines, COX-2, and iNOS gene expression were assessed using polymerase chain reaction techniques. Cytokines, COX-2, and iNOS gene expression were assessed using polymerase chain reaction techniques. High-performance liquid chromatography revealed that CAO was rich in acteoside and isoacteoside. As a result, CAO inhibited the generation of NO, cytokines, COX-2, and iNOS expression. Further, translocation to the nuclear of NF-κB p65 and degradation of the inhibitor of NF-кB (IкB) were alleviated by suppressing phosphorylation. Additionally, CAO significantly impacted MAPK pathway activation by potentially reducing phosphorylation of MAPKs. These results indicate that the anti-inflammatory effect of CAO is mediated via the inhibition of MAPK, PI3K/Akt, and NF-κB signaling pathways, probably via glycosides, phenolics, and flavonoids bioactivity derived from plants. CAO can serve as a potential anti-inflammatory agent, which alleviates inflammation factors and act through specific cell signaling pathways.

PPARγ is not required for the inhibitory actions of PGJ2 on cytokine signaling in pancreatic β-cells

2004 ◽  
Vol 286 (3) ◽  
pp. E329-E336 ◽  
Author(s):  
Sarah M. Weber ◽  
Anna L. Scarim ◽  
John A. Corbett
Keyword(s):  
Gene Expression ◽  
Nitric Oxide ◽  
Cytokine Signaling ◽  
Rinm5f Cells ◽  
Β Cells ◽  
Pancreatic Β Cells ◽  
Inos Gene ◽  
Ifn Γ ◽  
Anti Inflammatory ◽  
Inos Gene Expression

Peroxisome proliferator-activated receptor (PPAR)γ agonists, such as 15-deoxy-Δ12,14-prostaglandin J2 (PGJ2) and troglitazone, have been shown to elicit anti-inflammatory effects in pancreatic β-cells that include inhibition of cytokine-stimulated inducible nitric oxide synthase (iNOS) gene expression and production of nitric oxide. In addition, these ligands impair IL-1-induced NF-κB and MAPK as well as IFN-γ-stimulated signal transducer and activator of transcription (STAT)1 activation in β-cells. The purpose of this study was to determine if PPARγ activation participates in the anti-inflammatory actions of PGJ2 in β-cells. Pretreatment of RINm5F cells for 6 h with PGJ2 results in inhibition of IL-1-stimulated IκB degradation and IFN-γ-stimulated STAT1 phosphorylation. Overexpression of a dominant-negative (dn) PPARγ mutant or treatment with the PPARγ antagonist GW-9662 does not modulate the inhibitory actions of PGJ2 on cytokine signaling in RINm5F cells. Although these agents fail to attenuate the inhibitory actions of PGJ2 on cytokine signaling, they do inhibit PGJ2-stimulated PPARγ response element reporter activity. Consistent with the inability to attenuate the inhibitory actions of PGJ2 on cytokine signaling, neither dnPPARγ nor GW-9662 prevents the inhibitory actions of PGJ2 on IL-1-stimulated iNOS gene expression or nitric oxide production by RINm5F cells. These findings support a PPARγ-independent mechanism by which PPARγ ligands impair cytokine signaling and iNOS expression by islets.

scholarly journals Increased colonic iNOS gene expression from sustained Western‐style diet exposure

2010 ◽  
Vol 24 (S1) ◽  
Author(s):  
Ella M Zimmerly ◽  
Hyeran Jang ◽  
Julia Sauer ◽  
Sang‐Woon Choi
Keyword(s):  
Gene Expression ◽  
Inos Gene ◽  
Diet Exposure ◽  
Inos Gene Expression

scholarly journals Effects of Lycopene, Indole-3-Carbinol, and Luteolin on Nitric Oxide Production and iNOS Expression are Organ-Specific in Rats

2010 ◽  
Vol 61 (3) ◽  
pp. 275-285 ◽  
Author(s):  
Evita Rostoka ◽  
Sergejs Isajevs ◽  
Larisa Baumane ◽  
Aija Line ◽  
Karina Silina ◽  
...  
Keyword(s):  
Gene Expression ◽  
Brain Cortex ◽  
Natural Compounds ◽  
Inos Expression ◽  
No Production ◽  
Nitric Oxide Production ◽  
Inos Gene ◽  
Organ Specific ◽  
The Brain ◽  
Inos Gene Expression

Effects of Lycopene, Indole-3-Carbinol, and Luteolin on Nitric Oxide Production and iNOS Expression are Organ-Specific in RatsNatural compounds are known to modify NO content in tissues; however, the biological activity of polyphenol-rich food often does not correspond to the effects of individual polyphenols on NO synthase activity. The aim of this study was to see how natural compounds luteolin, indole-3-carbinol, and lycopene modify NO production in rat tissues and change the expression of the iNOS gene and protein. Indole-3-carbinol produced multiple effects on the NO level; it significantly decreased NO concentration in blood, lungs, and skeletal muscles and increased it in the liver. Indole-3-carbinol enhanced lipopolyssaccharide (LPS)-induced NO production in all rat organs. It decreased iNOS gene expression in the brain cortex of animals that did not receive LPS and up-regulated it in the LPS-treated animals. Lycopene increased the iNOS gene transcription rate in the brain cortex of LPS-treated animals. Luteolin did not modify NO production in any organ of LPS-untreated rats, nor did it affect gene expression in the liver. In the brain it slightly decreased iNOS gene expression. Luteolin decreased NO production in the blood of LPS-treated animals and the number of iNOS-positive cells in these animals. Our results suggest that changes in tissue NO levels caused by natural compounds cannot be predicted from their effect on NOS expression or activity obtained in model systems. This stresses the importance of direct measurements of NO and NOS expression in animal tissues.

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