Endotoxin protection against oxygen-induced acute and chronic lung injury

Small dosages of endotoxin (100--500 micrograms/kg) provide significant protection against the acute manifestations of pulmonary O2 toxicity and lethality. Ninety-seven percent of endotoxin-treated adult rats survived a 72-h exposure to greater than or equal to 95% O2 with mimimal lung changes, compared to 32% of control animals (P less than 0.01). Exposure to greater than or equal to 95% O2 for 7 days resulted in a 20% survival rate in untreated control rats vs. 98% survival in endotoxin-treated rats (P LESS THan 0.01). Histological evaluation of lung from survivors revealed substantially less collagen and reticular fiber deposition in the endotoxin-treated animal lungs. Endotoxin treatment was associated with increased activity of the protectant antioxidant enzyme systems of the lung in an apparent dose-response manner. Endotoxin's protective activity against O2 toxicity does not appear to depend on an initial toxic insult to the lung like with alpha-naphthylthiourea, oleic acid, or alloxan treatment. The data support a protective role for endotoxin against the acute and the more chronic manifestations of O2-induced pulmonary injury.

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Faculty Opinions recommendation of A protective role for IL-13 receptor α 1 in bleomycin-induced pulmonary injury and repair.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.725625029.793533115 ◽

2017 ◽

Author(s):

Nicola Heller

Keyword(s):

Protective Role ◽

Pulmonary Injury ◽

Injury And Repair

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The Impact of L-Carnitine and Coenzyme Q10 as Protection Against Busulfan-Oxidative Stress in the Liver of Adult Rats

The Natural Products Journal ◽

10.2174/2210315509666190723131511 ◽

2020 ◽

Vol 10 (5) ◽

pp. 578-586

Author(s):

Areeg M. Abdelrazek ◽

Shimaa A. Haredy

Keyword(s):

Oxidative Stress ◽

Coenzyme Q10 ◽

Protective Role ◽

Albino Rats ◽

Distilled Water ◽

Negative Effects ◽

Adult Rats ◽

Stress Damage ◽

The Impact ◽

Liver Tissues

Background: Busulfan (Bu) is an anticancer drug with a variety of adverse effects for cancer patients. Oxidative stress has been considered as a common pathological mechanism and it has a key role in the initiation and progression of liver injury by Bu. Aim: The study aimed to evaluate the antioxidant impact of L-Carnitine and Coenzyme Q10 and their protective role against oxidative stress damage in liver tissues. Methods and Material: Thirty-six albino rats were divided equally into six groups. G1 (con), received I.P. injection of DMSO plus 1 ml of distilled water daily by oral gavages; G2 (Bu), received I.P. injection of Bu plus 1 ml of the distilled water daily; G3 (L-Car), received 1 ml of L-Car orally; G4 (Bu + L-Car) received I.P. injection of Bu plus 1 ml of L-Car, G5 (CoQ10) 1 ml of CoQ10 daily; and G6 (Bu + CoQ10) received I.P. injection of Bu plus 1 ml of CoQ10 daily. Results: The recent data showed that Bu induced significant (P<0.05) elevation in serum ALT, AST, liver GSSG, NO, MDA and 8-OHDG, while showing significant (P<0.05) decrease in liver GSH and ATP. On the other hand, L-Carnitine and Coenzyme Q10 ameliorated the negative effects prompted by Bu. Immunohistochemical expression of caspase-3 in liver tissues reported pathological alterations in Bu group while also showed significant recovery in L-Car more than CoQ10. Conclusion: L-Car, as well as CoQ10, can enhance the hepatotoxic effects of Bu by promoting energy production in oxidative phosphorylation process and by scavenging the free radicals.

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Changes in Adult Rats’ Testis structure Induced by Hypothyroidism and Alleviating Role of L-Carnitine

International Journal of Human Anatomy ◽

10.14302/issn.2577-2279.ijha-19-3026 ◽

2019 ◽

Vol 1 (4) ◽

pp. 13-28

Author(s):

Abdelmonem Awad Hegazy ◽

Manal Mohammad Morsy ◽

Rania Said Moawad ◽

Gehad Mohammad Elsayed

Keyword(s):

Fatty Acids ◽

Semen Analysis ◽

Protective Role ◽

The Body ◽

Albino Rats ◽

Adult Rats ◽

Fatty Acids Metabolism ◽

Group 3 ◽

Group 2

Background Hypothyroidism is a metabolic disorder affecting the functions of many tissues in the body including the testis. Testis is rich in the polyunsaturated fatty acids content and lacks strong intrinsic antioxidant system making it prone to such oxidative stress. L-carnitine (LC) regulates long chain fatty acids metabolism; and is considered a valuable antioxidant factor. Aim It was to evaluate the effect of hypothyroidism induced by propylthiouracil (PTU) on rats’ testes and the possible protective role of LC. Methods Forty-eight adult male albino rats were used in this work. The animals were divided into three groups with sixteen animals in each. Group 1 (Control): Animals were kept without medications. Group 2 (PTU-treated): was subjected to administration of PTU; while group 3 (PTU and LC) received both PTU and LC. By the end of the experiment “30 days”, blood samples were taken for hormonal assay; then animals were anaesthetized and sacrificed. Specimens were homogenized for biochemical analysis; epididymal content of each rat was obtained immediately for semen analysis. Testes’ specimens were harvested, prepared and examined by light microscope examination. Results Induced hypothyroidism was noticed to cause histopathological, morphometric and biochemical changes in rat’s testes. LC protected the testicular specimens against such changes; it also improved the seminal quality and quantity as well as testicular structure and biochemistry. Conclusion Hypothyroidism could result in hazards to the structure of testis. Fortunately co-administration of LC might reduce such hazards.

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GPER mediates estrogen cardioprotection against epinephrine-induced stress

Journal of Endocrinology ◽

10.1530/joe-20-0451 ◽

2021 ◽

Author(s):

Lu Fu ◽

Hongyuan Zhang ◽

Jeremiah Ong’achwa Machuki ◽

Tingting Zhang ◽

Lin Han ◽

...

Keyword(s):

Culture Supernatant ◽

Cyclic Adenosine Monophosphate ◽

Adenosine Monophosphate ◽

Protective Role ◽

Left Ventricular ◽

Internal Diameter ◽

High Dose ◽

Adult Rats ◽

Rat Cardiomyocytes ◽

Lactate Dehydrogenase Release

Currently, there are no conventional treatments for stress-induced cardiomyopathy (SCM, also known as Takotsubo syndrome), and the existing therapies are not effective. The recently discovered G protein- coupled estrogen receptor (GPER) executes the rapid effects of estrogen (E2). In this study, we investigated the effects and mechanism of GPER on epinephrine (Epi)-induced cardiac stress. SCM was developed with a high dose of Epi in adult rats and human-induced pluripotent stem cells–derived cardiomyocytes(hiPSC-CMs). (1) GPER activation with agonist G1/ E2 prevented an increase in left ventricular internal diameter at end-systole, the decrease both in ejection fraction and cardiomyocyte shortening amplitude elicited by Epi. (2) G1/ E2 mitigated heart injury induced by Epi, as revealed by reduced plasma brain natriuretic peptide and lactate dehydrogenase release into culture supernatant. (3) G1/E2 prevented the raised phosphorylation and internalization of β2-adrenergic receptors（β2AR）. (4) Blocking Gαi abolished the cardiomyocyte contractile inhibition by Epi. G1/E2 downregulated Gαi activity of cardiomyocytes and further upregulated cyclic adenosine monophosphate concentration in culture supernatant treated with Epi. (5) G1/E2 rescued decreased Ca2+ amplitude and Ca2+ channel current (ICa-L) in rat cardiomyocytes. Notably, the above effects of E2 were blocked by the GPER antagonist, G15. In hiPSC-CM (which expressed GPER, β1AR and β2ARs), knockdown of GPER by siRNA abolished E2 effects on increasing ICa-L and action potential duration in the stress state. In conclusion, GPER played a protective role against SCM. Mechanistically, this effect was mediated by balancing the coupling of β2AR to the Gαs and Gαi signalling pathways.

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Abstract 13469: Drp1 Accumulates in Mitochondria and Plays a Protective Role in the Heart in Response to Pressure Overload

Circulation ◽

10.1161/circ.130.suppl_2.13469 ◽

2014 ◽

Vol 130 (suppl_2) ◽

Author(s):

Akihiro Shirakabe ◽

Yoshiyuki Ikeda ◽

Peiyong Zai ◽

Junichi Sadoshima

Keyword(s):

Diastolic Pressure ◽

Pressure Overload ◽

Protective Role ◽

Left Ventricular ◽

Multiple Time ◽

Lung Weight ◽

Knock Out ◽

Multiple Time Points ◽

Increased Activity ◽

Adaptive Role

Dynamin-related protein 1 (Drp1) plays an essential role in maintaining the quality control of mitochondria through mitochondrial (Mt) fission and mitophagy. We investigated how Mt function, autophagy and Drp1 are regulated in the heart during pressure overload (PO) and whether endogenous Drp1 plays an important role in regulating cardiac function. Mice were subjected to transverse aortic constriction (TAC) at multiple time points between 6 hours and 30 days. Left ventricular (LV) weight/tibial length (LVW/TL) was significantly elevated at Day 7 (TAC vs sham; 5.92 ± 0.27 vs 4.22 ± 0.12, p<0.05). Ejection fraction (EF) was maintained at Day 7, but gradually decreased thereafter (at 30 days; 65±9 vs 83±9 %, p<0.05). LC3-II was decreased (-45.7%, p<0.05) while p62 accumulated (1.17 fold, p<0.05) significantly at Day 7. Both Mt ATP content (-65.6%, p<0.05) and production (-90.3%, p<0.05) were reduced significantly at Days 7 and 14, respectively, and thereafter. Mt mass, evaluated by electron microscopy, was also reduced (-19.9%, p<0.05) at Day 7. Drp1 accumulated in mitochondria at Day 7, and S616 phosphorylation of Drp1, associated with increased activity, was increased at Day 7. Thus, PO suppresses autophagy and induces Mt dysfunction by Day 7, at which time Drp1 accumulates in mitochondria and Mt mass is decreased. To examine the functional significance of endogenous Drp1 during PO, cardiac-specific heterozygous Drp1 knock out (Drp-hetCKO) mice were subjected to TAC. At Day 7, decreases in EF (61± 2 vs 84 ± 7%, p<0.05) and increases in LVW/TL (7.22 ± 0.26 vs 5.86 ± 0.65, p<0.05) and lung weight/TL (12.01 ± 1.10 vs 6.31 ± 1.19, p<0.05) were exacerbated in Drp-hetCKO compared to in control mice. LV end diastolic pressure was significantly higher (22.0 ± 2.8 vs 5.7 ± 2.9 mmHg, p<0.05) and myocardial fibrosis (14.1 ± 2.5 vs 6.2 ± 4.3 %, p<0.05) was greater in Drp-hetCKO than in control mice. Mt mass was also significantly greater in Drp-hetCKO than in control mice (relative Mt mass, 1.21 ± 0.46 vs 1.00 ± 0.02, p<0.05). These results suggest that PO inhibits autophagy and induces mitochondrial dysfunction by Day7, which coincides with Mt accumulation of Drp1. Drp1 plays an adaptive role in this condition, mediating decreases in Mt mass and protecting the heart from dysfunction.

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THE EFFECTS OF SOME DIETARY DERIVED LIPIDS AND FAT SOLUBLE VITAMINS ON RAT SERUM TRIBUTYRINASE AND ALKALINE PHOSPHATASE

Canadian Journal of Medical Sciences ◽

10.1139/cjms52-039 ◽

1952 ◽

Vol 30 (4) ◽

pp. 308-313

Author(s):

Jack D. Taylor ◽

Neil B. Madsen ◽

Jules Tuba

Keyword(s):

Fatty Acids ◽

Alkaline Phosphatase ◽

Oleic Acid ◽

Stearic Acid ◽

Serum Alkaline Phosphatase ◽

Adult Rats ◽

Rat Serum ◽

Low Levels ◽

Fat Soluble Vitamins ◽

Increased Activity

Synthetic diets were fed to adult rats for four weeks to determine the effects of dietary stearic acid, oleic acid, glycerol, Crisco, and vitamins, A, D, and E on the activity of serum alkaline phosphatase and serum tributyrinase. On a diet devoid of fats or fatty acids, the rats manifested abnormally low enzyme levels, which for serum alkaline phosphatase fell to values characteristic of starvation. Basal levels of the two enzymes, obtained with a fat free diet, were not altered by the ingestion of glycerol or vitamins A, D, and E. Dietary stearic acid, oleic acid, and Crisco, each significantly increased activity of phosphatase and tributyrinase and it would appear that both enzymes are concerned with intestinal absorption of fatty acids. The effect of oleic acid was most pronounced with both enzymes. The rats all gained weight during the tests so none of the variations in enzyme levels can be attributed to inanition. After the dietary test periods, all groups were starved for one week. Serum phosphatase values fell to the same constant low levels for all animals. Tributyrinase values rose towards levels which suggest that the enzyme is concerned with mobilization of depot fats during periods of fasting.

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ULTRAMORPHOMETRIC STUDIES OF THE ADRENAL CORTEX OF ADULT RATS AFTER NEONATAL ADMINISTRATION OF SEX STEROIDS

Acta Endocrinologica ◽

10.1530/acta.0.0810537 ◽

1976 ◽

Vol 81 (2) ◽

pp. 537-547 ◽

Cited By ~ 2

Author(s):

E. Mäusle ◽

G. Fickinger

Keyword(s):

Sex Steroids ◽

Smooth Endoplasmic Reticulum ◽

Zona Fasciculata ◽

Sprague Dawley ◽

Adult Rats ◽

Sprague Dawley Rats ◽

Neonatal Administration ◽

The Individual ◽

Increased Activity ◽

Functional Reaction

ABSTRACT The outer zona fasciculata of 28 Sprague-Dawley rats, 8 weeks old, was studied by means of ultramorphometry. Four males and 4 females each received 1250 μg of testosterone proprionate (TP) or 300 μg oestradiol benzoate (OeB) on the second day of life. Four males and 4 females in oestrus or dioestrus served as controls. The controls showed both sex and cyclic differences: in comparison to the males, females displayed a finely dispersed lipoid pattern; enlargement of the nucleus and an increase in the amount of smooth endoplasmic reticulum (SER) indicated an increased stimulation of the cortex during oestrus. Neonatal administration of TP in females causes a distinct enlargement of cells with an increase in the volumes of nucleus, mitochondria, liposomes, SER and liposomes. The mitochondria and liposomes show a small-dispersed pattern of distribution. All these function-specific morphometric parameters point to an increased activity of the individual cell. The changes are less pronounced after OeB than after TP. In the male, neonatal administration of sex steroids results in an alteration of the sizes of the mitochondria and liposomes. The liposomes are distributed finely dispersed. At the same time there is an increase in the lipoid content. According to these parameters, fasciculata cells fulfil the morphological conditions that are a prerequisite for an elevated functional reaction. This change is more marked following OeB than TP. Sex dimorphism is preserved following neonatal application of sex steroids since the alterations are much more pronounced in females than in males.

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Platelets are necessary for airway wall remodeling in a murine model of chronic allergic inflammation

Blood ◽

10.1182/blood-2003-05-1707 ◽

2004 ◽

Vol 103 (2) ◽

pp. 639-647 ◽

Cited By ~ 86

Author(s):

Simon C. Pitchford ◽

Yanira Riffo-Vasquez ◽

Ana Sousa ◽

Stefania Momi ◽

Paolo Gresele ◽

...

Keyword(s):

Murine Model ◽

Airway Remodeling ◽

Allergic Inflammation ◽

Leukocyte Recruitment ◽

Corticosteroid Administration ◽

Reticular Fiber ◽

Allergic Lung Inflammation ◽

Fiber Deposition ◽

Subepithelial Fibrosis ◽

Platelet Depletion

Abstract Asthma is associated with airway remodeling. Evidence of platelet recruitment to the lungs of asthmatics after allergen exposure suggests platelets participate in various aspects of asthma; although their importance is unknown in the context of airway remodeling, their involvement in atherosclerosis is established. Studies from our laboratory have shown a requirement for platelets in pulmonary leukocyte recruitment in a murine model of allergic lung inflammation. Presently, the effects of platelet depletion and corticosteroid administration on airway remodeling and lung function were examined. Ovalbumin (OVA)–sensitized mice, exposed to aerosolized OVA for 8 weeks, demonstrated epithelial and smooth muscle thickening, and subepithelial reticular fiber deposition in the distal airways. The depletion of platelets via an immunologic (antiplatelet antisera) or nonimmunologic (busulfan) method, markedly reduced airway remodeling. In contrast, dexamethasone administration did not affect epithelial thickening or subepithelial fibrosis, despite significantly inhibiting leukocyte recruitment. Thus, pathways leading to certain aspects of airway remodeling may not depend on leukocyte recruitment, whereas platelet activation is obligatory. OVA-sensitized mice exhibited airway hyperresponsiveness (AHR) compared with shamsensitized mice following chronic OVA exposure. Neither platelet depletion nor dexamethasone administration inhibited chronic AHR; thus, mechanisms other than inflammation and airway remodeling may be involved in the pathogenesis of chronic AHR.

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Atrazine-induced degranulation of thyroid mast cells in peripubertal and adult rats

Open Life Sciences ◽

10.2478/s11535-011-0100-2 ◽

2012 ◽

Vol 7 (1) ◽

pp. 25-32 ◽

Cited By ~ 1

Author(s):

Vesna Rajkovic ◽

Renata Kovac ◽

Ivana Koledin ◽

Milica Matavulj

Keyword(s):

Mast Cell ◽

Mast Cells ◽

Reproductive Toxicity ◽

Age Groups ◽

Volume Density ◽

Histochemical Staining ◽

Histological Evaluation ◽

Numerical Density ◽

Adult Rats ◽

Endocrine Disrupting Chemical

AbstractAtrazine is a commonly used pesticide in the US and the non-EU countries. It is classified as an endocrine-disrupting chemical and is well-known for its reproductive toxicity in mammals and lower vertebrates. The study on atrazine effects on thyroid mast cells was performed on juvenile/peripubertal and adult male Wistar rats orally gavaged with atrazine at doses of 50 mg/kg of body weight (bw) or 200 mg/kg bw. In order to visualize the mast cell population within the thyroid gland, a histochemical staining method of toluidine blue was used. The results of the histological evaluation demonstrated a prominent increase in mast cell degranulation in both age groups and at both atrazine doses. According to the stereological analysis, a statistically significant decrease in the mast cell volume density in the young rats exposed to a higher dose of atrazine was found when compared to the corresponding control. The numerical density of mast cells significantly decreased in a higher-dose atrazine treated adults in comparison to the control. The obtained data suggest that atrazine-affected mast cells would probably have a consequent influence on thyroid follicular cells and/or thyroid microvasculature via paracrine action of released mediators, but might also be involved in already suggested thyroid cancerogenesis.

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