Prevention of cyclosporin nephrotoxicity with a platelet-activating factor (PAF) antagonist

Bagnis, C. Isnard; Deray, Gilbert; Dubois, M.; Pirotzky, E.; Jacquiaud, Claude; Baghos, W.; Aupetit, B.; Braquet, P.; Jacobs, C

doi:10.1093/ndt/11.3.507

Cited by 12 publications

(8 citation statements)

References 23 publications

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“…The ability of EGb761 to mediate the same favorable changes in major disease indicators as ASX is most likely due primarily to components of the mixture that block the PAF receptor, principally the terpene trilactones such as ginkgolide B (GB) (Bagnis et al , 1996; Brochet et al , 1999). Systemic inhibition of PAF‐dependent processes is expected to interrupt the pathogenesis of asthma at several checkpoints.…”

Section: Discussionmentioning

confidence: 99%

“…ASX and ginkgo extracts are minimally toxic (Bagnis et al , 1996; Haines et al , 2000; Mahmoud et al , 2002, 2004; Wang et al , 2000) and are marketed in the USA without prescription as components of food or food supplements. The present study demonstrates that oral administration of these phytonutrients to asthmatic animals along with vitamin C, significantly improved major indicators of asthma severity.…”

Section: Discussionmentioning

confidence: 99%

“…This molecule interacts with PAF receptors (PAFR) to cause release of cytosolic calcium from cellular stores, constituting a positive feedback process that amplifies immune cell activation and the severity of associated inflammatory pathologies (Asako et al , 1992; Sasakawa et al , 2000; Wenzel‐Seifert and Seifert, 1993). Compounds in Ginkgo extract (ginkgolides) that block PAFR thereby inhibiting increases of intracellular calcium, interrupt this process (Brochet et al , 1999), thereby allowing lower doses of drug to suppress calcium‐dependent activation events resulting in enhanced therapeutic outcomes (Bagnis et al 1996; Brochet et al , 1999; Haines et al , 2000).…”

Section: Introductionmentioning

confidence: 99%

“…The therapeutic effects of ginkgolides are due substantially to their ability to block PAF‐PAFR‐dependent calcium signaling, leading to prevention of inflammatory tissue damage (Bagnis et al , 1996; Brochet et al , 1999). ASX‐mediated cytoprotection occurs through a different mechanism, involving highly efficient scavenging of toxic reactive oxygen compounds by ASX, with the additional capacity to induce host antioxidant defenses (Kang et al , 2001; Wang et al , 2000).…”

Section: Introductionmentioning

confidence: 99%

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Summative interaction between astaxanthin, Ginkgo biloba extract (EGb761) and vitamin C in Suppression of respiratory inflammation: a comparison with ibuprofen

Haines

Varga

Bak

et al. 2010

Phytotherapy Research

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In this study, combinations of Ginkgo biloba leaf extract (EGb761) plus the carotenoid antioxidant astaxanthin (ASX) and vitamin C were evaluated for a summative dose effect in the inhibition of asthma‐associated inflammation in asthmatic guinea‐pigs. Ovalbumin‐sensitized Hartley guinea‐pigs challenged with ovalbumin aerosol to induce asthma, were administered EGb761, ASX, vitamin C or ibuprofen. Following killing, bronchoalveolar lavage (BAL) fluid was evaluated for inflammatory cell infiltrates and lung tissue cyclic nucleotide content. Each parameter measured was significantly altered to a greater degree by drug combinations, than by each component acting independently. An optimal combination was identified that included astaxanthin (10 mg/kg), vitamin C (200 mg/kg) and EGb761 (10 mg/kg), resulting in counts of eosinophils and neutrophils each 1.6‐fold lower; macrophages 1.8‐fold lower, cAMP 1.4‐fold higher; and cGMP 2.04‐fold higher than levels in untreated, asthmatic animals (p < 0.05). In conclusion, EGb761, ASX and vitamin C are shown here to interact summatively to suppress inflammation with efficacy equal to or better than ibuprofen, a widely used non‐steroidal antiinflammatory drug (NSAID). Such combinations of non‐toxic phytochemicals constitute powerful tools for the prevention of onset of acute and chronic inflammatory disease if consumed regularly by healthy individuals; and may also augment the effectiveness of therapy for those with established illness. Copyright © 2010 John Wiley & Sons, Ltd.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Summative interaction between astaxanthin, Ginkgo biloba extract (EGb761) and vitamin C in Suppression of respiratory inflammation: a comparison with ibuprofen

Haines

Varga

Bak

et al. 2010

Phytotherapy Research

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“…The process may also be inhibited by blocking PAF activity. Ginkgolides offer a desirable approach to this due to their low toxicity (34). Hence, their antiinflammatory properties offer high potential for therapeutic use.…”

Section: Discussionmentioning

confidence: 99%

In Vitro Effects of Astaxanthin Combined With Ginkgolide B on T Lymphocyte Activation in Peripheral Blood Mononuclear Cells From Asthmatic Subjects

et al. 2004

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Abstract. This study was undertaken to identify novel approaches to pharmacological treatment of asthma. Here we hypothesize that the platelet-activating factor receptor antagonist ginkgolide B (GB) in combination with the antioxidant carotenoid astaxanthin (ASX) suppresses T cell activation comparably to two commonly-used antihistamines: cetirizine dihydrochloride (CTZ) and azelastine (AZE). Peripheral blood mononuclear cells from asthmatics, cultured 24 h with either 50 mg / ml phytohemaglutinin (PHA) or PHA plus selected dosages of each drug are analyzed by flow cytometry for CD25+ or HLA-DR+ on CD3+ (T cells). Results are reported as stimulation indices (SI) of %CD3+CD25+ cells or %CD3+HLA-DR+ cells in cultures treated with PHA alone versus these subpopulations in cultures treated with both PHA and drugs. Combinations of ASX and GB exhibited optimal suppression at 10 -7 M GB + 10 -8 M ASX for CD3+CD25+ (SI = 0.79 ± 0.04, P = 0.001) and 10 -7 M GB + 10 -7 M ASX for CD3+HLA-DR+ (SI = 0.82 ± 0.05, P = 0.004). In conclusion, suppression of T cell activation below fully stimulated values by GB, ASX, and their combinations was comparable and for some combinations better than that mediated by CTZ and AZE. These results suggest that ASX and GB may have application as novel antiasthmatic formulations.

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Calcineurin inhibitors and sirolimus

Burdmann

Andoh

et al. 2003

Clinical Nephrotoxins

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Prevention of cyclosporin nephrotoxicity with a platelet-activating factor (PAF) antagonist

Abstract: We have demonstrated that the PAF antagonist BN 52021 can minimize the alteration of renal function induced by CsA.

Cited by 12 publications

References 23 publications

Summative interaction between astaxanthin, Ginkgo biloba extract (EGb761) and vitamin C in Suppression of respiratory inflammation: a comparison with ibuprofen

Summative interaction between astaxanthin, Ginkgo biloba extract (EGb761) and vitamin C in Suppression of respiratory inflammation: a comparison with ibuprofen

In Vitro Effects of Astaxanthin Combined With Ginkgolide B on T Lymphocyte Activation in Peripheral Blood Mononuclear Cells From Asthmatic Subjects

Calcineurin inhibitors and sirolimus

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