scholarly journals Arachidonic Acid Metabolites of CYP450 Enzymes and HIF-1α Modulate Endothelium-Dependent Vasorelaxation in Sprague-Dawley Rats under Acute and Intermittent Hyperbaric Oxygenation

2020 ◽  
Vol 21 (17) ◽  
pp. 6353
Author(s):  
Zrinka Mihaljević ◽  
Anita Matić ◽  
Ana Stupin ◽  
Ruža Frkanec ◽  
Branka Tavčar ◽  
...  
Keyword(s):  
Arachidonic Acid ◽  
Hyperbaric Oxygenation ◽  
Epoxyeicosatrienoic Acid ◽  
Sprague Dawley ◽  
Single Exposure ◽  
Ctrl Group ◽  
Sprague Dawley Rats ◽  
Acid Metabolites ◽  
Cox 1

Acetylcholine-induced vasorelaxation (AChIR) and responses to reduced pO2 (hypoxia-induced relaxation (HIR), 0% O2) were assessed in vitro in aortic rings of healthy male Sprague-Dawley rats (N = 252) under hyperbaric (HBO2) protocols. The studied groups consisted of the CTRL group (untreated); the A-HBO2 group (single HBO2; 120 min of 100% O2 at 2.0 bars); the 24H-HBO2 group (examined 24 h after single exposure) and the 4D-HBO2 group (four consecutive days of single HBO2). AChIR, sensitivity to ACh and iNOS expression were decreased in the A-HBO2 group. HIR was prostanoid- and epoxyeicosatrienoic acid (EET)-mediated. HIF-1α expression was increased in the 24H-HBO2 and 4D-HBO2 groups. LW6 (HIF-1α inhibitor) decreased HIR in the 24H-HBO2 group. HBO2 affected the expression of COX-1 and COX-2. CYP2c11 expression was elevated in the 24H-HBO2 and 4D-HBO2 groups. Concentrations of arachidonic acid (AA) metabolites 14(15)-DiHET, 11(12)-DiHET and 8(9)-DiHET were increased in A-HBO2 and 24H-HBO2. An increased concentration of 8(9)-EET was observed in the A-HBO2 and 24h-HBO2 groups vs. the CTRL and 4D-HBO2 groups, and an increased concentration of 5(6)-DiHET was observed in the 24H-HBO2 group vs. the 4D-HBO2 group. The 20-HETE concentration was increased in the A-HBO2 group. All were determined by LC-MS/MS of the aorta. The results show that AChIR in all groups is mostly NO-dependent. HIR is undoubtedly mediated by the CYP450 enzymes’ metabolites of AA, whereas HIF-1α contributes to restored HIR. Vasoconstrictor metabolites of CYP450 enzymes contribute to attenuated AChIR and HIR in A-HBO2.

Role of cytochrome P-450 in endogenous antipyresis

2000 ◽  
Vol 279 (2) ◽  
pp. R455-R460 ◽  
Author(s):  
Wieslaw Kozak ◽  
Matthew J. Kluger ◽  
Anna Kozak ◽  
Maciej Wachulec ◽  
Karol Dokladny
Keyword(s):  
Arachidonic Acid ◽  
Intraperitoneal Administration ◽  
Dependent Manner ◽  
Epoxyeicosatrienoic Acid ◽  
Sprague Dawley ◽  
Sprague Dawley Rats ◽  
Rats And Mice ◽  
Dose Dependent ◽  
Cytochrome P 450

In previous reports, we (15, 18) and others (29) demonstrated data showing that various inhibitors of cytochrome P-450/epoxygenase augment fever in rats and mice, indicating that the enzyme may be involved in endogenous antipyresis. The aim of this study was to further test the hypothesis that the P-450-dependent epoxygenase pathway of arachidonic acid is part of the homeostatic system to control the height of fever. Sprague-Dawley rats were implanted with biotelemeters to monitor body temperature. Fever was induced by intraperitoneal injection of lipopolysaccharide (LPS; 80 μg/kg). We demonstrate that intraperitoneal administration of P-450 inducers (bezafibrate and dehydroepiandrosterone, 10 and 100 mg/kg) before LPS reduced fever in rats in a dose-dependent manner. In complementary experiments, rats were implanted with brain cannulas in addition to the biotelemeters. Various isomers of epoxyeicosanoids were administered into the lateral ventricle at doses of 0.01 to 10 μg/rat to test their influence on LPS-induced fever in rats. Four of five isomers were antipyretic in a dose-dependent manner. The most potent antipyretic isomers were 11,12-epoxyeicosatrienoic acid (EET) followed by 14,15-EET, 8,9-EET, and 12(R) hydroxyeicosatetraenoic acid. These data support the hypothesis that the cytochrome P-450/epoxygenase pathway of arachidonate metabolism is part of the endogenous antipyretic system.

Hyperbaric oxygenation affects acetylcholine-induced relaxation in female diabetic rats

2019 ◽  
pp. 635-646
Author(s):  
Dragan Manojlović ◽  
◽  
Ana Stupin ◽  
Zrinka Mihaljević ◽  
Anita Matić ◽  
...  
Keyword(s):  
Hyperbaric Oxygenation ◽  
Thiobarbituric Acid ◽  
Diabetic Rats ◽  
Sprague Dawley ◽  
Systemic Oxidative Stress ◽  
Reducing Ability ◽  
Significant Difference ◽  
And Control ◽  
Cox 1

We aimed to assess the effects of intermittent hyperbaric oxygenation (HBO2 at 2 bars for 120 minutes a day for four successive days) on acetylcholine-induced vasorelaxation (AChIR) in female Sprague-Dawley (SD) rats (N=80) that were randomized into four groups: healthy controls (CTR); diabetic rats (DM); and control and diabetic rats that underwent hyperbaric oxygenation (CTR+HBO and DM+HBO), respectively. AChIR was measured in vitro in aortic rings, with/without L-NAME, MS-PPOH, HET0016 or indomethacin. mRNA expression of eNOS, iNOS, COX-1, COX-2, thromboxane A synthase 1 (TBXAS1), CYP4A1, CYP4A3 and CYP2J3 was assessed by qPCR. Systemic oxidative stress and plasma antioxidative capacity were determined with the thiobarbituric acid-reactive substances (TBARS) and the ferric reducing ability of plasma (FRAP) assays, respectively. There was no significant difference in AChIR among experimental groups of rats. In CTR and DM group of rats, AChIR was mediated by NO and EETs pathway, while in the CTR+HBO and DM+HBO groups, NO-pathway prevailed. iNOS expression was upregulated in the DM group compared to CTR, while HBO2 upregulated eNOS in CTR group and TBXAS1 in DM group of rats. In both, CTR and DM group of rats, the sensitivity to ACh in the presence of L-NAME or in the presence of MSPPOH was significantly decreased compared to the response to ACh in the absence or presence of indomethacin or HET0016. DM and DM+HBO rats had increased TBARS compared to their respective controls. In conclusion, HBO2 presumably alters vasorelaxation in response to ACh from NO-EETs mediated pathways to solely NO-pathway, without affecting oxidative status of DM rats.

scholarly journals Arachidonic acid in postshock mesenteric lymph induces pulmonary synthesis of leukotriene B4

2008 ◽  
Vol 104 (4) ◽  
pp. 1161-1166 ◽  
Author(s):  
Janeen R. Jordan ◽  
Ernest E. Moore ◽  
Eric L. Sarin ◽  
Sagar S. Damle ◽  
Sara B. Kashuk ◽  
...  
Keyword(s):  
Arachidonic Acid ◽  
Lung Injury ◽  
Ischemia Reperfusion ◽  
Leukotriene B4 ◽  
Polymorphonuclear Neutrophil ◽  
Sprague Dawley ◽  
Bioactive Lipids ◽  
Mesenteric Lymph ◽  
Sprague Dawley Rats

Mesenteric lymph is the mechanistic link between splanchnic hypoperfusion and acute lung injury (ALI), but the culprit mediator(s) remains elusive. Previous work has shown that administration of a phospholipase A2(PLA2) inhibitor attenuated postshock ALI and also identified a non-ionic lipid within the postshock mesenteric lymph (PSML) responsible for polymorphonuclear neutrophil (PMN) priming. Consequently, we hypothesized that gut-derived leukotriene B4(LTB4) is a key mediator in the pathogenesis of ALI. Trauma/hemorrhagic shock (T/HS) was induced in male Sprague-Dawley rats and the mesenteric duct cannulated for lymph collection/diversion. PSML, arachidonic acid (AA), and a LTB4receptor antagonist were added to PMNs in vitro. LC/MS/MS was employed to identify bioactive lipids in PSML and the lungs. T/HS increased AA in PSML and increased LTB4and PMNs in the lung. Lymph diversion decreased lung LTB4by 75% and PMNs by 40%. PSML stimulated PMN priming (11.56 ± 1.25 vs. 3.95 ± 0.29 nmol O2−/min; 3.75 × 105cells/ml; P < 0.01) that was attenuated by LTB4receptor blockade (2.64 ± 0.58; P < 0.01). AA stimulated PMNs to produce LTB4, and AA-induced PMN priming was attenuated by LTB4receptor antagonism. Collectively, these data indicate that splanchnic ischemia/reperfusion activates gut PLA2-mediated release of AA into the lymph where it is delivered to the lungs, provoking LTB4production and subsequent PMN-mediated lung injury.

scholarly journals Acute Hyperbaric Oxygenation, Contrary to Intermittent Hyperbaric Oxygenation, Adversely Affects Vasorelaxation in Healthy Sprague-Dawley Rats due to Increased Oxidative Stress

2018 ◽  
Vol 2018 ◽  
pp. 1-15 ◽  
Author(s):  
Zrinka Mihaljević ◽  
Anita Matić ◽  
Ana Stupin ◽  
Lidija Rašić ◽  
Ivana Jukić ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Nadph Oxidase ◽  
Mrna Expression ◽  
Hyperbaric Oxygenation ◽  
Antioxidative Enzyme ◽  
Superoxide Production ◽  
Sprague Dawley ◽  
Sprague Dawley Rats ◽  
Expression And Activity

The present study was aimed at assessing endothelium-dependent vasorelaxation, at measuring superoxide production in the aorta and femoral artery, and at determining antioxidative enzyme expression and activity in aortas of male Sprague-Dawley rats (N=135), randomized to an A-HBO2 group exposed to a single hyperbaric oxygenation session (120′ of 100% O2 at 2.0 bars), a 24H-HBO2 group (single session, examined 24 h after exposure), a 4D-HBO2 group (4 consecutive days of single sessions), and a CTRL group (untreated group). Vasorelaxation of aortic rings in response to acetylcholine (AChIR) and to reduced pO2 (HIR) was tested in vitro in the absence/presence of NOS inhibitor L-NAME and superoxide scavenger TEMPOL. eNOS, iNOS, antioxidative enzyme, and NADPH oxidase mRNA expression was assessed by qPCR. Serum oxidative stress markers and enzyme activity were assessed by spectrometry, and superoxide production was determined by DHE fluorescence. Impaired AChIR and HIR in the A-HBO2 group were restored by TEMPOL. L-NAME inhibited AChIR in all groups. Serum oxidative stress and superoxide production were increased in the A-HBO2 group compared to all other groups. The mRNA expression of iNOS was decreased in the A-HBO2 and 24H-HBO2 groups while SOD1 and 3 and NADPH oxidase were increased in the 4D-HBO2 group. The expression and activity of catalase and glutathione peroxidase were increased in the 4D-HBO2 group as well. AChIR was NO dependent. Acute HBO2 transiently impaired vasorelaxation due to increased oxidative stress. Vasorelaxation was restored and oxidative stress was normalized 24 h after the treatment.

scholarly journals Pharmacological comparison of four biopolymeric natural gums as hemostatic agents for management of bleeding wounds: preliminary in vitro and in vivo results

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Himanshu Kushwah ◽  
Nidhi Sandal ◽  
Meenakshi Chauhan ◽  
Gaurav Mittal
Keyword(s):  
Xanthan Gum ◽  
Guar Gum ◽  
Human Lymphocytes ◽  
Sprague Dawley ◽  
Gum Tragacanth ◽  
Civilian Trauma ◽  
Sprague Dawley Rats ◽  
Cytotoxicity Studies

Abstract Background Uncontrolled bleeding is one of the primary reasons for preventable death in both civilian trauma and military battle field. This study evaluates in vitro and in vivo hemostatic potential of four biopolymeric natural gums, namely, gum tragacanth, guar gum, xanthan gum, and gum acacia. In vitro evaluation of whole blood clotting time and erythrocyte agglutination assay were carried out. In vitro cytotoxicity studies with respect to each gum were done in human lymphocytes to ascertain percent cell viability. In vivo hemostatic potential of each gum (as sponge dressing and powder form) was evaluated in Sprague Dawley rats using tail bleeding assay and compared with commercially available hemostatic sponge. Other important parameters like (a) time taken for complete hemostasis, (b) amount of blood absorbed, (c) adherence strength of developed hemostatic dressing(s), (d) incidence of re-bleeding, and (e) survival of animals were also studied. Results Of the four test gums studied, xanthan gum (@3mg/ml of blood) and gum tragacanth (@35mg/ml of blood) were able to clot blood in least time (58.75±6.408 s and 59.00±2.082 s, respectively) and exhibited very good hemostatic potential in vitro. Except for xanthan gum, all other test gums did not exhibit any significant cytotoxicity at different time points till 24 h. In rat tail bleeding experiments, gum tragacanth sponge dressing and powder achieved hemostasis in least time (156.2±12.86 s and 76±12.55 s, respectively) and much earlier than commercially available product (333.3±38.84 s; p˂0.01). Conclusion Results indicate potential of gum tragacanth to be developed into a suitable hemostatic product.

Bioavailability in Vivo of Benzo[a]Pyrene Adsorbed to Diesel Particulate

1991 ◽  
Vol 7 (3) ◽  
pp. 125-139 ◽  
Author(s):  
David R. Bevan ◽  
David M. Ruggio
Keyword(s):  
Health Risks ◽  
Quantitative Description ◽  
Intratracheal Instillation ◽  
Direct Analysis ◽  
Sprague Dawley ◽  
Reasonable Estimate ◽  
Diesel Particulate ◽  
Sprague Dawley Rats

To evaluate health risks associated with exposure to particulates in the environment, it is necessary to quantify the bioavailability of carcinogens associated with the particulates. Direct analysis of bioavailability in vivo is most readily accomplished by adsorbing a radiolabeled form of the carcinogen to the particulate. A sam ple of native diesel particulate collected from an Oldsmobile die sel engine that contained 1.03 μ g benzo[ a] pyrene ( BaP)/ g particulate was supplemented with exogenous [ 3 H]- BaP to pro duce a particulate containing 2.62 μ g BaP/g. To insure that elu tion of BaP from native and [3 H] -BaP-supplemented particulate was similar, in vitro analyses were performed. When using phos pholipid vesicles composed of dimyristoylphosphatidylcholine (DMPC), 1.52% of total BaP was eluted from native particulate into the vesicles in 18 hrs; from [ 3 H] -BaP supplemented particu late, 1.68% was eluted. Using toluene as eluent, 2.55% was eluted from native particulate, and 8.25% from supplemented particulate, in 6 hrs. Supplemented particulate was then instilled intratracheally into male Sprague-Dawley rats and distribution of radioactivity was analyzed at selected times over 3 days. About 50% of radioactivity remained in lungs at 3 days following instil lation, with 30% being excreted into feces and the remainder dis tributed throughout the organs of the rats. To estimate the amount of radioactivity that entered feces through swallowing of a portion of the instilled dose, [3 H] -BaP-supplemented particu late was instilled intratracheally into rats that had a cannula sur gically implanted in the bile duct. Rate of elimination of radio activity into bile was monitored; 10.6% of radioactivity was re covered in 6 hr, an amount slightly lower than the 12.8% ex creted in 6 hrs into feces of animals with intact bile ducts. Our studies provide a quantitative description of the distribution of BaP and its metabolites following intratracheal instillation of diesel particulate. Because rates of elution of BaP in vitro are similar for native diesel particulate and particulate with supple mental [ 3H] -BaP, our results provide a reasonable estimate of the bioavailability in vivo of BaP associated with diesel particu late.

Safety Assessment of a Hydroethanolic Extract of Caralluma fimbriata

2013 ◽  
Vol 32 (5) ◽  
pp. 385-394 ◽  
Author(s):  
Antoinette Y. Odendaal ◽  
Narendra S. Deshmukh ◽  
Tennille K. Marx ◽  
Alexander G. Schauss ◽  
John R. Endres ◽  
...  
Keyword(s):  
Developmental Toxicity ◽  
Toxicity Study ◽  
Developmental Study ◽  
Sprague Dawley ◽  
Oral Toxicity ◽  
Toxicological Assessment ◽  
Sprague Dawley Rats ◽  
Chromosomal Aberration Test ◽  
Hydroethanolic Extract

This toxicological assessment evaluated the safety of a hydroethanolic extract prepared from Caralluma fimbriata (CFE), a dietary supplement marketed worldwide as an appetite suppressant. Studies included 2 in vitro genotoxicity assays, a repeated dose oral toxicity study, and a developmental study in rats. No evidence of in vitro mutagenicity or clastogenicity surfaced in the in vitro studies at concentrations up to 5000 μg of extract/plate (Ames test) or 5000 μg of extract/mL (chromosomal aberration test). No deaths or treatment-related toxicity were seen in the 6-month chronic oral toxicity study in Sprague-Dawley rats conducted at 3 doses (100, 300, and 1000 mg/kg body weight (bw)/d). The no observed effect level for CFE in this study was considered to be 1000 mg/kg bw/d. A prenatal developmental toxicity study conducted at 3 doses (250, 500, and 1000 mg/kg bw/d) in female Sprague-Dawley rats resulted in no treatment-related external, visceral, or skeletal fetal abnormalities, and no treatment-related maternal or pregnancy alterations were seen at and up to the maximum dose tested. CFE was not associated with any toxicity or adverse events.

Arachidonic acid metabolites induced β-adrenoceptor densitization in rat lung in vitro

1985 ◽  
Vol 30 (5) ◽  
pp. 799-809 ◽  
Author(s):  
Luisa Daffonchio ◽  
Maria Pia Abbracchio ◽  
Alicia Hernandez ◽  
Emanuela Giani ◽  
Flaminio Cattabeni ◽  
...  
Keyword(s):  
Arachidonic Acid ◽  
Rat Lung ◽  
Arachidonic Acid Metabolites ◽  
Acid Metabolites
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