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C J Doelman

Publications and source records attributed to C J Doelman.

12 recordsLinked to original sources
PubMed1991

Oxidants and antioxidants: state of the art.

Reactive oxygen species are regarded as merely pernicious. This is incorrect for they play a pivotal role in many physiologic reactions, such as cytochrome P450-mediated oxidations, regulation of the tone of smooth muscle, and killing of microorganisms. An imbalance in oxidant-antioxidant activity is involved in many free radical-mediated pathologies, e.g., ischemia-reperfusion and asthma. In an attempt to alleviate these pathologies with antioxidants, it should be noted that these compounds are neither specific nor mere antioxidants. Associated with antioxidant activity is a pro-oxidant action. In the development of new antioxidant therapies, the important question of how these drugs are incorporated in or commensurate with existing integrated physiologic radical-defense systems should be addressed.

Animals↗
PubMed1991

Prejunctional muscarinic receptors on cholinergic nerves in guinea pig airways are of the M2 subtype.

Prejunctional inhibitory muscarinic receptors in guinea pig tracheal strips were investigated by electrical field stimulation. Pilocarpine and methacholine caused, in a similar way, a dose-dependent increase in baseline with a concomitant decrease in twitch response. We showed by using selective muscarinic antagonists, such as pirenzepine (M1-selective), methoctramine (M2-selective), AF-DX 116 (11-[[2-[diethylamino)methyl]-1-piperidinyl]-acetyl]-5,11-dihydro- 6H-pyrido[2,3-b] [1,4]benzodiazepine-6-one, M2-selective), gallamine (M2-selective) and 4-DAMP (4-diphenylacetoxy-N- methylpiperidinemethiodide, M3-selective), that the prejunctional inhibitory muscarinic receptor is of the M2 subtype.

Animals↗
PubMed1990

Plasticisers, another burden for asthmatics?

The widely used plasticiser di(2-ethylhexyl)phthalate (DEHP) has been reported to have some toxicological effects on pulmonary tissue. Inhalation of DEHP may cause pulmonary edema and bronchial asthma. Moreover intravenous injection of DEHP induces pulmonary inflammation and hemorrhage of the lungs. We now report that DEHP might cause bronchial hyperresponsiveness. The metabolite of DEHP mono(2-ethylhexyl)phthalate (MEHP) induces in vitro a dose-dependent increase in -log EC50 for methacholine dose response curves in rat tracheal tissue. Moreover MEHP induces a decrease in maximal effect of the methacholine dose response curve. We concluded that DEHP due to the formation of MEHP in vivo, may cause bronchial hyperresponsiveness.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗
PubMed1990

Oxidative stress and receptor responses in guinea-pig tracheal tissue.

Reactive oxygen species are formed during inflammatory reactions in the lung. Alveolar macrophages and neutrophils and eosinophils produce superoxide anions, hydrogen peroxide, hydroxyl radicals and singlet oxygen. Neutrophils and eosinophils produce also hypochlorous acid. We now present the effects of hydrogen peroxide and hypochlorous acid on muscarinic and beta-adrenergic receptor responses of guinea pig tracheal tissue. Hydrogen peroxide (up to 10 mM) has no effect on these receptor responses, but in contrast hypochlorous acid destructs the muscarinic and beta-adrenergic receptor response. The beta-adrenergic receptor response is more susceptible to hypochlorous acid treatment than the muscarinic receptor response. This indicates that hypchlorous acid induces an autonomic imbalance between parasympatic and sympatic receptor responses in the guinea pig trachea.

Animals↗
PubMed1990

Oxygen radicals in lung pathology.

Pulmonary tissue can be damaged in different ways, for instance by xenobiotics (paraquat, butylated hydroxytoluene, bleomycin), during inflammation, ischemia reperfusion, or exposure to mineral dust or to normobaric pure oxygen levels. Reactive oxygen species are partly responsible for the observed pulmonary tissue damage. Several mechanisms leading to toxicity are described in this review. The reactive oxygen species induce bronchoconstriction, elevate mucus secretion, and cause microvascular leakage, which leads to edema formation. Reactive oxygen species even induce an autonomic imbalance between muscarinic receptor-mediated contraction and the beta-adrenergic-mediated relaxation of the pulmonary smooth muscle. Vitamin E and selenium have a regulatory role in this balance between these two receptor responses. The autonomic imbalance might be involved in the development of bronchial hyperresponsiveness, occurring in lung inflammation. Finally, several antioxidants are discussed which may be beneficial as therapeutics in several lung diseases.

Animals↗
PubMed1990

Regulation of sympathetic and parasympathetic receptor responses in the rat trachea by epithelium: influence of mechanical and chemical removal of epithelium.

Removal of the epithelial layer of rat tracheal tissue did not affect the methacholine-induced contraction of the tracheal smooth muscle, but attenuated the (-)-isoprenaline induced relaxation (expressed as percentage of the methacholine contraction). In this way the epithelial layer seemed to play a role in the maintenance of an autonomic balance between sympathetic and parasympathetic receptor responses. Incubation of rat tracheal tissue with cumene hydroperoxide (3 x 10(-5)-10(-3) M) resulted in a dose-dependent destruction and (partial) removal of the epithelial layer. Cumene hydroperoxide diminished muscarinic receptor responses of the rat trachea. Moreover, the autonomic balance between muscarinic and beta-adrenoceptor responses was affected. The effects of cumene hydroperoxide on receptor responses were more pronounced after epithelium removal. The protective role of the epithelial layer of pulmonary tissue against oxidative stress has therefore been emphasized.

Animals↗
PubMed1990

Mineral dust exposure and free radical-mediated lung damage.

Chronic exposure to several types of mineral dust particles induces an inflammatory reaction in the lung. Dust particles activate alveolar macrophages and prime leukocytes (neutrophils, eosinophils, and basophils), leading to an enhanced release of reactive oxygen species. Sometimes mineral dust particles also contain radicals. Reactive oxygen species (superoxide anion radical, hydrogen peroxide, hydroxyl radical, and singlet oxygen) may lead to tissue damage. These are able to break DNA strands, to destroy proteins, and to induce the process of lipid peroxidation. The effects of oxygen radicals on the beta-adrenergic and muscarinic receptor response of the guinea pig and rat tracheal strip are described. The beta-adrenergic receptor response appeared to be more susceptible to oxidative stress than the muscarinic receptor response. This may lead to an autonomic imbalance on exposure to oxygen radicals. The lipid peroxidation product 4-hydroxy-2,3-trans-nonenal diminished the beta-adrenergic responsiveness in guinea pig tracheal preparations. Histologic examinations indicated that at low concentrations of cumene hydroperoxide (10(-4) M) the epithelial layer of rat trachea was already destroyed, whereas no effect on the muscarinic response was found. Oxygen radical-mediated damage in lung tissue may lead to lung emphysema, hyperresponsiveness, and hypersensitivity. Pharmacotherapeutic interventions that prevent initiation or propagation of these free radical reactions may have a beneficial effect in mineral dust-associated lung disease.

Animals↗
PubMed1988

Vitamin E and selenium regulate balance between beta-adrenergic and muscarinic responses in rat lungs.

The effects of hydrogen peroxide on the beta-adrenergic and muscarinic responses of the rat trachea muscle were studied in vitro, after feeding rats, for 6 weeks, either a diet deficient in vitamin E and selenium or a control diet. In the control situation after incubation with 1 mM hydrogen peroxide for 30 min, a reduction of the maximal response to methacholine of 39% occurred whereas no pD2 shift could be demonstrated. Moreover, no response to isoprenaline after precontraction with 3 x 10(-7) M methacholine was left. In the deficient situation, we found a reduction to 64% of the response to methacholine after incubation with 1 mM hydrogen peroxide. Again isoprenaline became inactive, i.e. no relaxation with isoprenaline was observed after precontraction with 3 x 10(-7) M methacholine. We therefore conclude that vitamin E and selenium protect against oxidative stress in lung tissue and thus regulate the (patho-) physiological balance between adrenergic and muscarinic responses.

Animals↗
PubMed1987

A disbalance between beta-adrenergic and muscarinic responses caused by hydrogen peroxide in rat airways in vitro.

The effect of hydrogen peroxide on adrenergic and muscarinic responses of rat airway smooth muscle was studied. The trachea muscle and the lung parenchymal strip were contracted with methacholine and relaxed with (-)-isoprenaline. Recording of three (-)-isoprenaline curves on the trachea muscle and the lung parenchymal strip was followed by treatment for 30 min with hydrogen peroxide (H2O2) (1mM) after which a new dose response curve for (-)-isoprenaline was constructed. Using the trachea muscle this treatment with H2O2 resulted in a decrease of 61% of the maximum contraction by methacholine compared with the control and a complete inhibition of the relaxation by (-)-isoprenaline. In the lung parenchymal strip preparation we found, after the same treatment no reduction of the contraction by methacholine and 61% reduction of the relaxation by (-)-isoprenaline, compared with the control. The results demonstrate that the adrenergic response in rat airways is more susceptible to hydrogen peroxide than the muscarinic response.

Animals↗