Luteolin, quercetin, genistein and quercetagetin inhibit the effects of lipopolysaccharide obtained from Porphyromonas gingivalis in H9c2 cardiomyoblasts.

BACKGROUND: One of the microorganisms from dental plaque associated with severe inflammatory responses in infectious endocarditis is Porphyromonas gingivalis. It is a Gram-negative bacteria harvested from chronic periodontitis patients. Lipopolysaccharide (LPS) obtained from P. gingivalis promotes the expressions of interleukin-1 (IL-1), IL-6 and tumor necrosis factor alpha (TNF-α). Flavonoids are thought to participate in processes that control inflammation, such as the expression of cyclooxygenase-2 (COX-2). METHODS: We investigated the effects of luteolin, quercetin, genistein and quercetagetin on cardiomyoblasts treated with LPS alone or in combination with following inhibitors p38 (SB203580), ERK (PD98059), JNK (SP600125) and PKC (Calphostin C) for 1 h. The kinase activation and COX-2 expression levels were determined at the gene and protein levels. RESULTS: These flavonoids are considered to inhibit the activation of mitogen-activated protein kinase (MAPK) and the degradation of inhibitor of kappa B-alpha (IκB-α). They also play a role in COX-2 expression. CONCLUSION: We conclude that the tested flavonoids inhibit inflammatory responses induced by LPS in H9c2 cells.

Biochemical and molecular modulation of CCl4-induced peripheral and central damage by Tilia americana var. mexicanaextracts.

Around the world, species from the genus Tilia are commonly used because of their peripheral and central medicinal effects; they are prepared as teas and used as tranquilizing, anticonvulsant, and analgesic agents. In this study, we provide evidence of the protective effects of organic and aqueous extracts (100 mg/kg, i.p.) obtained from the leaves of Tilia americana var. mexicana on CCl4-induced liver and brain damage in the rat. Protection was observed in the liver and brain (cerebellum, cortex and cerebral hemispheres) by measuring the activity of antioxidant enzymes and levels of malondialdehyde (MDA) using spectrophotometric methods. Biochemical parameters were also assessed in serum samples from the CCl4-treated rats. The T. americana var. mexicana leaf extracts provided significant protection against CCl4-induced peripheral and central damage by increasing the activity of antioxidant enzymes, diminishing lipid peroxidation, and preventing alterations in biochemical serum parameters, such as the levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), γ-globulin (γ-GLOB), serum albumin (ALB), total bilirubin (BB), creatinine (CREA) and creatine kinase (CK), relative to the control group. Additionally, we correlated gene expression with antioxidant activity in the experimental groups treated with the organic and aqueous Tilia extracts and observed a non-statistically significant positive correlation. Our results provide evidence of the underlying biomedical properties of T. americana var. mexicana that confer its neuro- and hepatoprotective effects.

C-phycocyanin prevents cisplatin-induced mitochondrial dysfunction and oxidative stress.

The potential of C-phycocyanin (C-PC) to prevent cisplatin (CP)-induced kidney mitochondrial dysfunction was determined in CD-1 male mice. The CP-induced mitochondrial dysfunction was characterized by ultrastructural abnormalities and by decrease in the following parameters in isolated kidney mitochondria: adenosine diphosphate (ADP)-induced oxygen consumption (state 3), respiratory control ratio, ADP/oxygen (ADP/O) ratio, adenosine triphosphate synthesis, membrane potential, calcium retention, glutathione (GSH) content, and activity of respiratory complex I, aconitase, catalase, and GSH peroxidase. These mitochondria also showed increase in hydrogen peroxide production, malondialdehyde, and 3-nitrotyrosine protein adducts content. The above-described changes, as well as CP-induced nephrotoxicity, were attenuated in mice pretreated with a single injection of C-PC. Our data suggest that the attenuation of mitochondrial abnormalities is involved in the protective effect of C-PC against CP-induced nephrotoxicity. This is the first demonstration that C-PC pretreatment prevents CP-induced mitochondrial dysfunction in mice.

The modulation of the hexosamine biosynthetic pathway impacts the localization of CD36 in macrophages.

CD36 is a type 2 cell surface scavenger receptor expressed in various tissues. In macrophages, CD36 recognizes oxidized low-density lipoprotein (ox-LDL), which promotes the formation of foam cells, the first step toward an atherosclerotic arterial lesion. CD36 possesses a variety of posttranslational modifications, among them N-glycosylation and O-GlcNAc modification. Some of the roles of these modifications on CD36 are known, such as N-linked glycosylation, which provides proper folding and trafficking to the plasma membrane in the human embryonic kidney. This study aimed to determine whether variations in the availability of UDP-GlcNAc could impact Rab-5-mediated endocytic trafficking and, therefore, the cellular localization of CD36. These preliminary results suggest that the availability of the substrate UDP-GlcNAc, modulated in response to treatment with Thiamet G (TMG), OSMI-1 (O-GlcNAcylation enzymes modulators) or Azaserine (HBP modulator), influences the localization of CD36 in J774 macrophages, and the endocytic trafficking as evidenced by the regulatory protein Rab-5, between the plasma membrane and the cytoplasm.

Rutin Prevents LTA Induced Oxidative Changes in H9c2 Cells.

Lipoteichoic acid (LTA), a component of Gram-positive bacteria cell walls is involved in infective endocarditis (IE), a life-threatening disease. We evaluated for the first time, whether flavonoid rutin (quercetin-3-rutinoside) can block LTA-induced pro-inflammatory response and reactive oxygen species (ROS) production, and reduction of antioxidant enzymes. We found that rutin suppresses LTA effects on the antioxidant enzymes superoxide dismutase, catalase, and glutathione peroxidase, as well as the pro-inflammatory enzyme cyclooxygenase-2, preventing phosphorylation of the mitogen-activated protein kinases (MAPKs), p38, and c-Jun N-terminal kinase, and the increase of ROS production induced by LTA. Taken together, these findings suggest that rutin prevents oxidative damage, inflammation, and MAPKs activation induced by LTA. Rutin may exert a protective effect in IE. These data provide novel insights for future use of rutin to prevent the mechanisms of LTA-related pathogenesis, inflammatory processes, and antioxidant enzyme levels in diseases such as IE.

Lipoteichoic acid reduces antioxidant enzymes in H9c2 cells.

Infective endocarditis (IE) is an illness where the heart is invaded by bacteria, like Streptococcal and Staphylococcal species that contain lipoteichoic acid (LTA) related to an essential role in this disease. This study is the first in evaluating antioxidant enzyme levels in embryonic cardiomyocyte cell line (H9c2) induced by LTA from Streptococcus sanguinis. LTA increased reactive oxygen species (ROS) and reduced the levels of the antioxidant enzymes glutathione peroxidase, superoxide dismutase (SOD)-1 and catalase (CAT) but did not affect glutathione content. At the highest LTA concentration (15 µg/ml), SOD-1 and CAT levels did not change, and this effect was related to the induction of mRNA levels of Nrf2 induced by LTA. These results suggest that low antioxidant enzyme levels and ROS production could be related to IE.

Flavonoids exert multiple periodontic benefits including anti-inflammatory, periodontal ligament-supporting, and alveolar bone-preserving effects.

Flavonoids are plant-derived polyphenolic compounds claimed to help alleviate a variety of conditions, including diabetes, infectious endocarditis, and cancer. They have attracted substantial research interest as nutraceuticals owing to their diverse bioactivities. Periodontitis is a high-incidence inflammatory disease affecting the dentition-supporting periodontium. Although the etiology of periodontitis is diverse, microbial species in dental plaque are considered its main pathogenic agents. Here, we provide a review of flavonoid study findings relevant for periodontitis treatment and prevention. Cell biology and in vivo rodent model studies have revealed a multiple of flavonoid effects on periodontal cells and tissues, including regulation of inflammatory responses in periodontal components and potential preserving effects in periodontal ligament and alveolar bone tissues. Mechanistic studies have indicated that flavonoids may counteract the proinflammatory effects exerted by pathogen-associated molecular patterns (PAMP) proteins through Toll-like receptor (TLR) responses. Potentially beneficial effects of flavonoids have been reported for various periodontium cells, including epithelial gingival cells, gingival fibroblasts, and periodontal ligament fibroblasts, as well as for alveolar bone maintaining osteoblasts. The findings indicate that flavonoids are highly promising clinical agents for the prevention and reduction of periodontitis, which can be delivered easily to patients via mouthwash, toothpaste, and food products.

Curcumin prevents paracetamol-induced liver mitochondrial alterations.

OBJECTIVE: In the present study was evaluated if curcumin is able to attenuate paracetamol (PCM)-induced mitochondrial alterations in liver of mice. METHODS: Mice (n = 5-6/group) received curcumin (35, 50 or 100 mg/kg bw) 90 min before PCM injection (350 mg/kg bw). Plasma activity of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) was measured; histological analyses were done; and measurement of mitochondrial oxygen consumption, mitochondrial membrane potential, ATP synthesis, aconitase activity and activity of respiratory complexes was carried out. KEY FINDINGS: Curcumin prevented in a dose-dependent manner PCM-induced liver damage. Curcumin (100 mg/kg) attenuated PCM-induced liver histological damage (damaged hepatocytes from 28.3 ± 7.7 to 8.3 ± 0.7%) and increment in plasma ALT (from 2300 ± 150 to 690 ± 28 U/l) and AST (from 1603 ± 43 to 379 ± 22 U/l) activity. Moreover, curcumin attenuated the decrease in oxygen consumption using either succinate or malate/glutamate as substrates (evaluated by state 3, respiratory control ratio, uncoupled respiration and adenosine diphosphate/oxygen ratio), in membrane potential, in ATP synthesis, in aconitase activity and in the activity of respiratory complexes I, III and IV. CONCLUSIONS: These results indicate that the protective effect of curcumin in PCM-induced hepatotoxicity is associated with attenuation of mitochondrial dysfunction.

C-phycocyanin prevents cisplatin-induced nephrotoxicity through inhibition of oxidative stress.

The aim of this study was to evaluate whether the antioxidant C-phycocyanin (C-PC, 5-30 mg kg(-1) i.p.) was able to prevent cisplatin (CP, 18 mg kg(-1) i.p.) induced nephrotoxicity by reducing oxidative stress in CD-1 mice. Nephrotoxicity was assessed by measuring blood urea nitrogen, plasma glutathione peroxidase, plasma creatinine, the renal activity of N-acetyl-ß-d-glucosaminidase, apoptosis and histopathological changes. Oxidative stress was evaluated by measuring the content of glutathione, malondialdehyde, 4-hydroxynonenal and oxidized proteins in renal tissue. C-PC prevented CP-induced renal damage and oxidative stress in a dose-dependent manner. Moreover, C-PC prevented the decrease in the renal activity of the antioxidant enzymes glutathione peroxidase, glutathione reductase, glutathione-S-transferase and catalase induced by cisplatin. In vitro assays showed that C-PC was an effective scavenger of the following reactive species: hypochlorous acid, peroxynitrite anions, peroxyl radicals, diphenyl-1-picrylhydrazyl, hydroxyl radicals, superoxide anions, singlet oxygen and hydrogen peroxide. It is concluded that the protective effect of the nutraceutical C-PC against CP-induced nephrotoxicity was associated with the attenuation of oxidative stress and the preservation of the activity of antioxidant enzymes.

Comparison of antioxidant activity of hydroethanolic fresh and aged garlic extracts and their effects on cerebral ischemia.

Antioxidant properties and protective effect of aged garlic extract (AGE) and of 20% hydroethanolic fresh extracts from garlic clove (GCE) and skin (GSE) on cerebral ischemia were evaluated by administering extracts at the beginning of reperfusion in a rat model of stroke. All three extracts scavenged superoxide anion, peroxynitrite anion, and peroxyl radicals, but with different efficiencies; furthermore, GCE and GSE scavenged hydroxyl radicals and GSE scavenged singlet oxygen. These extracts significantly prevented reduction of neuronal nuclear antigen in the infarcted area, although no improvement in neurological function was observed. Importantly, GCE and GSE contained S-allylcystein, a compound associated with AGE's neuroprotective effect against damage induced by cerebral ischemia. Extracts decreased mRNA expression of NR1- and NR2B-NMDA-receptor subunits and prevented ischemia-induced reduction in mitochondrial potential and in ATP synthesis. These results indicate that antioxidants present in garlic extracts may regulate ROS concentrations during ischemia, favour pro-survival pathways, and attenuate mitochondrial dysfunction.