Iron chelation effects on lipid peroxidation, inflammation and ventricular performance in a rat model of isoproterenol induced acute myocardial stress.

Acute cardiac pathologies represent one of the leading causes of death, while iron metabolism is recognized to be implicated in reactive oxygen species production, lipid peroxidation, and inflammation. The aim of the present study was to assess iron chelation effects in isoproterenol (ISO) induced acute cardiac stress. We divided male Wistar rats into preventive and secondary treatment groups, with the active arm consisting in deferiprone (DFP), a lipid permeable chelator. Mortality of ISO was 10-18.18% in both preventive and secondary groups. We analyzed serum and myocardial tissue parameters of inflammation, iron dynamics, and lipid peroxidation, accompanied by ultramicroscopy, histological, and ultrasound-derived parameters of left ventricular function. Results reveal that ISO-mediated lipid peroxidation and inflammation are alleviated by administration of DFP, with negligible effect on systemic ferroregulation dynamics and global ventricular function (as assessed by ultrasound). DFP administration after cardiovascular stress is associated with a decrease in lipid peroxidation and inflammation, without an improvement in gross left ventricular parameters.

Chronic oral trimethylamine-N-oxide administration induces experimental incipient atherosclerosis in non-genetically modified mice.

Atherosclerosis is a chronic inflammatory disease of the arterial wall involving inflammation, redox imbalance, and impaired cholesterol transport. A high level of trimethylamine-N-oxide (TMAO) produced by meat and fat metabolism are involved in atherosclerosis development, but the exact relationship with inflammation is not completely clear. The study aimed to identify a possible association between TMAO; atherosclerotic changes in the aortic root; oxidative stress; and inflammation quantified by highly sensitive C-reactive protein (hsCRP), tumor necrosis factor alpha (TNF-α), and interleukin-1beta (IL-1ß) levels. TMAO dihydrate was administered via gastric gavage to 20 male Wistar rats for 90 days; one separate group received vehicle. The TMAO-treated animals were divided into two groups: one group received a low dose of TMAO (20 mg/day) and the other group received a high dose of TMAO (40 mg/day). Malondialdehyde (MDA), proinflammatory markers - IL-1ß, TNF-α, and hsCRP, total cholesterol, high-density lipoprotein (HDL)-cholesterol, triglycerides, and glucose were assessed 30 and 90 days after TMAO administration. Additionally, conventional histopathology and immunohistochemistry for collagen I distribution were performed. MDA, hsCRP, TNF-α, and IL-1ß levels increased after 90 days of TMAO administration in conjunction with significant changes suggestive of incipient atherosclerosis and inflammation of the aortic root. The increase was higher in the group treated with 40 mg/day TMAO compared with the group treated with 20 mg/day TMAO. Additionally, blood levels of TMAO were significantly correlated with hsCRP, TNF-α, IL-1ß levels, but also with MDA, low HDL-cholesterol levels, and high triglyceride levels. The increase in MDA and inflammatory cytokines and modification of lipid metabolism markers may explain the pro-atherogenic effect of TMAO.

The impact of Sambucus nigra L. extract on inflammation, oxidative stress and tissue remodeling in a rat model of lipopolysaccharide-induced subacute rhinosinusitis.

Rhinosinusitis is a common disorder related to inflammation of paranasal sinuses and nasal cavity mucosa. Herbal medicines could be an option in the treatment of rhinosinusitis due to their anti-inflammatory and anti-oxidative properties. The study aims to investigate the effect of intranasal Sambucus nigra L. subsp. nigra (SN) extract against inflammation, oxidative stress, and tissue remodeling in nasal and sinus mucosa, but also in serum, lungs, and brain, in Wistar rat model of subacute sinonasal inflammation induced by local administration of lipopolysaccharides (LPS), from Escherichia Coli. The cytokines (TNF-α, IL-1ß, IL-6) and oxidative stress (malondialdehyde) in nasal mucosa, blood, lungs, and brain were analyzed. In addition, a histopathological examination was performed, and NF-kB, MMP2, MMP9, TIMP1 expressions were also evaluated in nasal mucosa. Both doses of LPS increased the production of cytokines in all the investigated tissues, especially in the nasal mucosa and blood (p < 0.01 and p < 0.05), and stimulated their secretion in the lungs, and partially in the brain. Malondialdehyde increased in all the investigated tissues (p < 0.01 and p < 0.05). In parallel, upregulation of NF-kB and MMP2 expressions with downregulation of TIMP1, particularly at high dose of LPS, was observed. SN extract reduced the local inflammatory response, maintained low levels of IL-6, TNF-α, and IL-1ß. In lungs, SN reduced all cytokines levels while in the brain, the protective effect was noticed only on IL-6. Additionally, SN diminished lipid peroxidation and downregulated NF-kB in animals exposed to a low dose of LPS, with increased TIMP1 expression, while in animals treated with a high dose of LPS, SN increased NF-kB, MMP2, and MMP9 levels. In conclusion, SN extract diminished the inflammatory response, reduced generation of reactive oxygen species (ROS) and, influenced MMPs expressions, suggesting the benficial effect of SN extract on tissue remodeling in subacute rhinosinusitis and on systemic inflammatory response.

Biomarkers of pediatric obstructive sleep apnea syndrome and the assessment of quality of life before and after adenotonsillectomy.

The study aims to explore the inflammatory cytokines and oxidative stress in children with obstructive sleep apnea syndrome (OSAS) triggered by adenoids and/or tonsillar hypertrophy and their changes after adenotonsillectomy (AT) and to investigate the associated behavioral disorders in OSAS, before and after AT. Thirty patients with OSAS and 20 healthy children, aged 3 - 13 years were included in the study. According to apnea-hypopnea index (AHI), OSAS children were classified into 3 groups: mild (n = 19), moderate (n = 5), and severe OSAS (n = 6). Erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), interleukin (IL)-6, tumor necrosis factor (TNF)-α, malondialdehyde (MDA) and antioxidant enzymes activities were assessed in serum, preoperative and 6 weeks after AT. TNF-α, IL-6 and malondialdehyde levels were also estimated in adenoid and tonsils tissues. A Pediatric Sleep Questionnaire was completed by the parents before and after AT. As a result of the study, we obtained the following results: TNF-α, IL-6 and malondialdehyde evaluated preoperative increased in serum and tissues in OSAS, especially in severe disease compared to mild and moderate forms. Six weeks after AT, AHI diminished significantly in OSAS, as well as the inflammatory markers and malondialdehyde, in parallel with significant improvement of antioxidant enzymes activities. Daytime sleepiness, hyperactivity and attention deficit in OSAS, even in mild disease were present, with significant improvements of obstructive symptoms after AT. We conclude that OSAS caused by adenoids and/or tonsillar hypertrophy led to changes in the blood parameters, with significant improvement after AT. Postoperatively, a significant improvement in sleep quality and behavior in OSAS patients was also observed.

Quercetin attenuates naso-sinusal inflammation and inflammatory response in lungs and brain on an experimental model of acute rhinosinusitis in rats.

This study aimed to investigate the effect of quercetin without intranasal inflammation and oxidative stress in nasal and sinus mucosa, but also in serum, lungs and brain in a rat model of acute nasal and sinus inflammation induced by administration of lipopolysaccharides (LPS) (from Escherichia coli). Wistar rats were divided into five groups of 10 animals each. The control group received an intranasal saline solution once/day, for seven consecutive days. Rats in groups 2 and 3, received low-dose (5 µg) and high-dose (10 µg) of LPS, once/day, for seven consecutive days. Rats in groups 4 and 5, received low-dose (5 µg) and high-dose (10 µg) of LPS and after 2 h, 80 mg/kg of quercetin, once/day for seven consecutive days was administered. After the treatment period, the histopathological examination of nasal and sinus mucosa was performed and levels of cytokines (tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß), interleukin-6 (IL-6)) and oxidative stress in the blood, nasal mucosa, lungs and brain were also analyzed. High dose of LPS increased TNF-α, IL-6 and IL-1ß levels in serum, nasal mucosa, and lungs homogenates while in brain, this effect was only on TNF-α levels. IL-1ß enhanced significantly in serum and mucosa, especially after administration of a high dose of LPS (P < 0.01 and P < 0.05). Histopathological and immunofluorescence analysis revealed acute inflammatory reaction in rats treated with both doses of LPS without significant changes of lipid peroxidation in the studied tissues. Quercetin administration diminished the exudate and degree of inflammation in lamina propria of nasal and sinusal areas, parallel with the decreased secretion of TNF-α (40.2% reduction after the low dose of LPS, and 35.4% reduction after the high dose of LPS) and IL-6 (21.4% reduction after the low dose of LPS and 35.8% reduction after the high dose of LPS). In lungs, quercetin reduced TNF-α (43.3%) and IL-6 levels (24.5%), and in the brain, the protective effect was noticed only on TNF-α (46.5%). The intranasal LPS administration successfully induced acute rhinosinusitis in a rat model and also generated an inflammatory response in the lungs and brain. Intranasal administration of quercetin diminished the nasal inflammation and also exerted protective effect on lungs and partially on brain inflammatory reaction.

Characterization and biological effects of Hypericum extracts on experimentally-induced - anxiety, oxidative stress and inflammation in rats.

Anxiety disorders can associate with oxidative stress and immune system alterations. Our study aimed to chemically analyze Hypericum maculatum (HM) and Hypericum perforatum (HP) dry extracts and to evaluate their effects along with quercetin (Q), on brain oxidative stress biomarkers: malondialdehyde (MDA), catalase (CAT) and superoxide dismutase (SOD), inflammatory cytokines: interleukin-1α, (IL-1α), IL-1ß, regulated on activation normal T cell expressed and secreted (RANTES), interferon (IFN), monocyte chemoattractant protein-1 (MCP1), macrophage inflammatory protein (MIP) and serum corticosterone levels. Nuclear transcription factor κB (NFκB) signaling pathway in the hippocampus and frontal lobe in rats with N-methyl-9H-pyrido[5,4-b]indole-3-carboxamide (FG-7142) experimental-induced anxiety were also investigated. The chemical analyses of total hypericins were performed by spectrophotometric analysis and hypericin, hyperforin and polyphenols derivatives were quantified by chromatographic methods. The animals were divided in 6 groups: carboxymethylcellulose 2% (CMC); CMC + FG; alprazolam (APZ) + FG; Q + FG; HM + FG; HP + FG. APZ (0.08 mg/kg b.w.), Q (30 mg/kg b.w.), HM and HP (350 mg/kg b.w.) were orally administered for 21 days. FG (7.5 mg/kg b.w.) was intraperitoneally (i.p.) injected in a single dose. Q and hypericum extracts (HpE) exerted anti-inflammatory (decreased IL-1α, IL-1ß, MCP1, IFN and MIP mainly in hippocampus) and antioxidant effects (decreased MDA levels, increased CAT and SOD activity), enhanced NFκB and pNFκB expressions in the brain and reduced serum corticosterone levels. Our findings suggest that HpE may improve anxiety-like behavior, offer brain protection by modulation of oxidative stress and inflammation, and can contribute to overall biological activity of natural compounds-rich diet.

Oxidative stress in blood and testicle of rat following intraperitoneal administration of aluminum and indium.

Aluminum (Al) and indium (In) have embryotoxic, neurotoxic and genotoxic effects, oxidative stress being one of the possible mechanisms involved in their cytotoxicity. We have recently demonstrated that indium intraperitoneal (ip) administration induced histological disorganization of testicular tissue. In the present research we aimed at investigating the effect of Al and In ip administration on systemic and testicular oxidative stress status. Studies were performed on Wistar rats ip injected with Al, In or physiological solution for two weeks. Our results showed that In significantly decreased the absolute weight of testicles. Measurements of lactate dehydrogenase (LDH) and paraoxonase (PON) activities showed that In induced a significant augmentation in the first parameter but no changes were observed in the second. Both Al and In caused oxidative stress in testicles by increasing malondialdehyde (MDA) and protein carbonyls (PC) production. Concomitantly, thiol group (-SH) and glutathione (GSH) level were enhanced in the testicles. In the blood, while concentrations of MDA was not changed, those of GSH was significantly decreased in the Al and In groups. Our results indicated that Al and In cause oxidative stress both in blood and testicles but In has cytotoxic effect as well as negative impact on testicle weights. These findings could explain the testicular histological alterations previously described after In ip administration.

The effects of chitosan and low dose dexamethasone on extrahepatic cholestasis after bile duct ligation in Wistar rats.

UNLABELLED: Inflammation and oxidative stress are important pathways in the development of liver fibrosis following biliary obstruction. AIM: To evaluate the effects of low dose dexamethasone and chitosan, a natural compound with no side-effects, on liver damage caused by bile duct ligation in rats. MATERIALS AND METHODS: Fifty female Wistar rats, randomly and equally divided in 5 groups: I (SHAM) underwent only laparotomy, II (BDL) with bile duct ligation, III (DEX) 0.125 mg/kg dexamethasone i.m. daily, IV (CS) 1 mg/kg chitosan by gavage and group V (DEX+CS), both substances. After six days, the following parameters were assessed from liver homogenates: malondialdehyde (MDA), protein carbonyls (PC), reduced glutathione (GSH), total SH groupings, nitric oxide (NO), and from plasma: MDA, γ-glutamyltranspeptidase (GGT), alanine aminotransferase (ALT), aspartate aminotransferase (AST), and total bilirubin (TB). A histopathological examination was performed using some of the elements of the Knodell Histological Activity Index. RESULTS: BDL significantly increases the levels of MDA, liver enzymes, and the necro-inflammatory score compared to the sham group and it decreases the antioxidant capacity. DEX protects against lipid peroxidation and improves the antioxidant capacity, but it is not able to protect the hepatocytes. Chitosan significantly decreases (p<0.05) the levels of MDA (0.07±0.01 vs 0.10±0.01 nmoles/mg protein BDL group, p=0.027) and also ALT, TB, GGT and reduces liver necrosis and inflammation (2.75±0.95 vs 1±0, p<0.05). Both CS and DEX reduce the level of NO significantly. CONCLUSION: BDL induces severe oxidative stress damage after six days already. Chitosan proved very efficient in protecting the hepatocytes against oxidative stress, a fact supported by the histological findings.

Non-invasive oxidative stress markers for liver fibrosis development in the evolution of toxic hepatitis.

Oxidative stress is related to the liver fibrosis, anticipating the hepatic stellate cells' (HSC) activation. Our aim was to correlate oxidative stress markers with the histological liver alterations in order to identify predictive, noninvasive parameters of fibrosis progression in the evolution of toxic hepatitis.CCl4 in sunflower oil was administered to rats intragastrically, twice a week. After 2, 3, 4 and 8 weeks of treatment, plasma levels of malondialdehyde (MDA), protein carbonyls (PC), hydrogen donor capacity (HD), sulfhydryl groups (SH), and glutathione (GSH) were measured and histological examination of the liver slides was performed. Dynamics of histological disorders was assessed by The Knodell score. Significant elevation of inflammation grade was obtained after the second week of the experiment only (p=0.001), while fibrosis started to become significant (p=0.001) after 1 month of CCl4 administration. Between plasma MDA and liver fibrosis development a good correlation was obtained (r=0.877, p=0.05). Correlation between PC dynamics and liver alterations was marginally significant for inflammation grade (r=0.756, p=0.138). HD evolution revealed a marginally inverse correlation with inflammation grade (r=-0.794, p=0.108). No correlations could be established for other parameters with either inflammation grade or fibrosis stage.Our study shows that MDA elevation offers the best prediction potential for fibrosis, while marginal prediction fiability could be attributed to high levels of plasma PC and low levels of HD.

Blood oxidative stress generation after intraperitoneal administration of functionalized single-walled carbon nanotubes in rats.

Single-walled carbon nanotubes (SWCNTs) have been proposed for various medical applications. However, their safety for human administration has not been yet fully demonstrated. In vitro studies have pointed oxidative stress as a mechanism involved in their cytotoxic effects. In the present study we have evaluated the capacity of DNA functionalized SWCNTs to induce oxidative stress in blood after intraperitoneal (ip) administration in rats. The presence of SWCNTs in blood was confirmed by Raman spectroscopy 30 minutes after their ip administration. Oxidative stress parameters (malondialdehyde - MDA, protein carbonyls - PC, antioxidant capacity measured as hydrogen donating capacity - HD, sulfhydryl groups - SH, glutathione - GSH and nitrites - NO) were assessed in blood at 3, 6, 24, respectively, and 48 hours after ip injection. MDA, PC and NO exhibited a significant increase at 3-6 hours interval from exposure, followed by a recovery trend. The levels of HD reached a bottom level at 6 hours after administration, while SH strongly decreased at 3 hours interval and increased slightly up to 48 hours without attending the initial values. GSH level recorded an increasing tendency at the 3rd hour, an incomplete recovery process at 24 hours followed by a secondary significant increase following a 48-hour interval. Significant inverse correlations were obtained between the PC and SH levels and between the NO and HD values. In conclusion, the ip administration of DNA functionalized SWCNT in rats results in oxidative stress generation in plasma, with a transient pattern of evolution.

Oxidative photodamage induced by photodynamic therapy with methoxyphenyl porphyrin derivatives in tumour-bearing rats.

The oxidative effects of photodynamic therapy with 5,10,15,20-tetrakis(4-methoxyphenyl) porphyrin (TMP) and Zn-5,10,15,20-tetrakis(4-methoxyphenyl) porphyrin (ZnTMP) were evaluated in Wistar rats subcutaneously inoculated with Walker 256 carcinoma. The animals were irradiated with red light (λ = 685 nm; D = 50 J/cm2; 15 min) 3 h after intra-peritoneal administration of 10 mg/kg body weight of porphyrins. The presence of free radicals in tumours after photodynamic therapy with TMP and ZnTMP revealed by chemiluminescence of luminol attained the highest level at 18 h after irradiation. Lipid peroxides measured as thiobarbituric-reactive substances and protein carbonyls, which are indices of oxidative effects produced on susceptible biomolecules, were significantly increased in tumour tissues of animals 24 h after photodynamic therapy. The levels of thiol groups and total antioxidant capacity in the tumours were decreased. The activities of antioxidant enzymes superoxide dismutase and glutathione peroxidase were also increased in tumour tissues after photodynamic therapy. Increased levels of plasma lipid peroxides as well as changes in the levels of erythrocyte antioxidant enzyme activities suggest possible systemic effects of photodynamic therapy with TMP and ZnTMP.

Studies on antioxidant effects of the red grapes seed extract from Vitis vinifera, Burgund Mare, Recas in pregnant rats.

To estimate the effects of hydroethanolic red grapes seeds extract obtained from Vitis vinifera, Burgund Mare variety, Recas , Romania (BMR) on oxidant-antioxidant ballance, as compared to ascorbic acid, during pregnancy in rats. Thirty Wistar female rats were assigned to three groups (n=10) which were administered by gavage: Group I, 3 x 100 mg/kg body weight saline, Group II - BMR 3 x 30 mg gallic acid equivalents/kg body weight; Group III - vitamin C 3 x 100 mg/kg body weight on days 1, 7 and 14 of pregnancy. On day 21 blood samples were collected. Malon dyaldehyde, lipid peroxides, protein carbonyls, nitric oxide (as oxidative stress parameters) and hydrogen donor ability and total thiol groups (as antioxidant parameters) serum concentrations were measured. Vitamin C significantly enhanced the antioxidant capacity of plasma (hydrogen donor ability, p=0.0001; thiol groups, p=0.0001), as well as nitric oxide levels (p=0.001). The extract increased the plasma antioxidant capacity (hydrogen donor ability, p=0.001; thiol groups p=0.001) and did not elevate the nitric oxide plasma levels in pregnant rats.In conclusion, in the chosen dose, the red grapes seed extract enhanced the plasma antioxidant capacity and did not influence the nitric oxide levels in pregnant rats.