Protective effect of a specific platelet activating factor antagonist, BN 52021, on bupivacaine-induced cardiovascular impairments in rats

Lagente, Vincent; Simonetti, Maria P.B.; Fortes, Zuleica Bruno; Braquet, P.

doi:10.1016/1043-6618(89)90199-0

Cited by 2 publications

(1 citation statement)

References 27 publications

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“…Initially, the potential of ginkgolides as cardioprotectants has been investigated via the recognized activity of GkB as an anti-PAF agent [Berti et al, 1989;Koltai et al, 1989;Lagente et al, 1989;Wainwright and Parratt, 1989]. The involvement of PAF in cardiovascular pathophysiological processes is well established [Montrucchio et al, 2000].…”

Section: Biologymentioning

confidence: 98%

Influence of lipophilicity and stereochemistry at the C7 position on the cardioprotective and antioxidant effect of ginkgolides during rat heart ischemia and reperfusion

Billottet¹,

Martel

Culcasi³

et al. 2005

Drug Dev. Res.

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The extent to which the cardioprotective effect of ginkgolides is related to their lipophilicity rather than to their anti-platelet activating factor (PAF) effect was addressed in isolated rat hearts submitted to ischemia and reperfusion. A new derivative of ginkgolide C (1), the 7-a-O-(4-methylphenyl) ginkgolide C (4) was synthesized and compared to 7-O-(4-methylphenyl) ginkgolide C (2) that had the same absolute configuration at C 7 as 1 for its lipophilicity, anti-PAF activity, and cardioprotective and antioxidant effects. Using reversed-phase high-performance liquid chromatography HPLC, 4 and 2 were found to be significantly more lipophilic (i.e., log k w of 3.4270.05 and 3.6470.07, respectively) than 1 (1.1570.03) and the strong PAF inhibitor ginkgolide B (GkB; 1.6570.03). The anti-PAF activities (IC 50 values in mM) were 8.2, 17.1, and 2.2 for 4, 1, and GkB, respectively, while 2 was inactive. In preischemic and/or reperfused hearts perfused with ginkgolides at 0.7 mM: (i) 2 and 4 were more efficient in improving postischemic hemodynamic and metabolic recovery than 1, (ii) a key-step in cardioprotection occurred during ischemia where 2 and 4 limited myocardial ATP depletion and contracture development, (iii) a strong anti-lipoperoxidant effect was observed with 2 and 4, but not 1. In vivo administration of 2 to rats (4 mg/kg/day for 20 days) was more effective than that of 1 regarding ischemic heart protection, suggesting a positive role for lipophilicity. It was concluded that a high lipophilicity is not an absolute prerequisite for a strong anti-PAF effect for ginkgolides, whereas it appears essential for cardioprotection. Drug Dev. Res. 64:157-171, 2005.

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Section: Biologymentioning

confidence: 98%