Effect of an adenosine receptor antagonist on acute amphotericin B nephrotoxicity

Kuan, Chia-Jen; Branch, Robert A.; Jackson, Edwin K.

doi:10.1016/0014-2999(90)90107-h

Cited by 13 publications

(5 citation statements)

References 11 publications

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“…The vasoconstricting action of AmB can be counteracted with the methylxanthine aminophylline (32,51). Pentoxifylline has vasodilating activity on constricted blood vessels that is equal to that of aminophylline (26).…”

Section: Resultsmentioning

confidence: 99%

Pentoxifylline modulates activation of human neutrophils by amphotericin B in vitro

Sullivan

Carper

Mandell

1992

Antimicrob Agents Chemother

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a second stimulus. AmB also stimulates mononuclear leukocytes (MNLs) to release inflammatory mediators which augment the effects of AmB on PMN function. In the present study, we observed that the methylxanthine derivative pentoxifylline decreased the effects of AmB on PMN function. AmB (2 ,ug/ml) priming doubled PMN chemiluminescence stimulated by fMet-Leu-Phe. In the presence of MNLs, AmB priming increasedjMet-Leu-Phe-stimulated PMN chemiluminescence to 622% of unprimed PMN activity. Pentoxifylline (100 ,uM) blunted the rise in AmB-augmented PMN chemiluminescence in the presence of MNLs to 282% of unprimed PMN activity, and pentoxifylline metabolites were active at 10 ,IM. Pentoxifylline (100 ,uM) also blocked AmB-augmented PMN oxidative activity in whole blood, as measured by nitroblue tetrazolium reduction. In the presence of MNL, AmB (2 ,ug/ml) doubled the expression of the important PMN adherence factor Mac-1. Pentoxifylline (1 mM) decreased AmB-stimulated PMN Mac-i expression back to unstimulated amounts. In the presence of MNLs, AmB (2 jig/ml) decreased PMN nondirected and directed migration to fMet-Leu-Phe to 40 and 38% of control PMN migration, respectively. Pentoxifylline (300 ,uM) counteracted AmB inhibition of nondirected and directed migration to fMet-Leu-Phe, resulting in migration that was 71 and 87% of control PMN migration, respectively. In contrast, the methylxanthine caffeine (100 ,iM) increased AmB-enhanced chemiluminescence but did not affect AmBinhibited PMN migration. Pentoxifylline should be evaluated as adjunctive therapy to lessen the inflammatory damage caused by AmB.The antifungal agent amphotericin B (AmB) has a stimulatory effect on several polymorphonuclear leukocyte (PMN) functions. AmB increases PMN adherence to nylon wool, PMN aggregation (5,9,10,35,40,69), and PMN oxidative activity (59). AmB also activates macrophages (15,34,48,66,67) and induces the production of tumor necrosis factor alpha (TNF-ot) and interleukin-1 beta 8) (17,25). We have observed that the presence of mononuclear leukocytes (MNLs) exacerbates the inflammatory effects of AmB on PMN function, including AmB priming of the PMN oxidative burst and PMN expression of the adherence inte-

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Section: Resultsmentioning

confidence: 99%

Pentoxifylline modulates activation of human neutrophils by amphotericin B in vitro

Sullivan

Carper

Mandell

1992

Antimicrob Agents Chemother

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“…These include adenosine receptor duced significant stress to render the kidney salt blockade, phosphodiesterase inhibition, and changes in inIn contrast, the salt-loaded group had elevated tracellular calcium levels (17). cessful in antagonizing the RBF-lowering effects of amphotericin B (13). Using AMP-CP as an alternative pharmacological probe of the role of adenosine, we were also unable to substantially alter the response to amphotericin B. Conversely, there was a tendency for AMP-CP to potentiate the response.…”

Section: Resultsmentioning

confidence: 99%

Mechanisms of amphotericin B-induced decrease in glomerular filtration rate in rats

Sabra

Branch

1991

Antimicrob Agents Chemother

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Mechanisms responsible for the reductions in renal blood flow (RBF) and glomerular filtration rate (GFR) in response to acute infusions of amphotericin B were investigated in vivo in rats. The influence of salt status and the roles of adenosine, cyclic AMP, and calcium influx were examined. Amphotericin B was infused into the renal artery in seven groups of rats at 0.025 mg/kg of body weight per min for 15 min. RBF Amphotericin B infusions induce acute reductions in renal blood flow (RBF) and glomerular filtration rate (GFR) in both rats and dogs (4, 9, 11), due mostly to elevation of renovascular resistance (21). The mechanisms underlying these acute hemodynamic effects have not been completely elucidated. Studies with dogs have suggested that activation of tubuloglomerular feedback (TGF) plays a role in these changes, since both TGF and amphotericin B-induced decreases in GFR are inhibited by the same pharmacologic interventions (salt loading, furosemide, or theophylline administration) (1,7,8,24,31). Unfortunately, these studies were conducted with different species (dogs for amphotericin B and rats for TGF). It is not clear whether both species behave similarly with respect to both TGF and amphotericin B. Therefore, it is important to examine this question since, if true, it would lend greater support to the hypothesis.In chronic models of nephrotoxicity in the rat, salt loading attenuates the decreases in GFR induced by amphotericin B, while salt depletion potentiates them (16, 28). In addition, there are hemodynamic changes similar to those observed after acute infusions of the drug (28). At present, the effect of salt status on the acute renal response of the rat to amphotericin B is unknown, but it is possible that the acute hemodynamic effects of amphotericin B may contribute to the deterioration in renal function observed in chronic models. In order to examine this possibility and to further study the role of TGF, we decided to assess the influence of salt status on the acute responses to amphotericin B in rats.Theophylline inhibits the GFR-lowering effects of both * Corresponding author.TGF activation in rats (17,18) and amphotericin B in dogs (9), but its effect on the amphotericin B response in rats is not known. In the case of TGF, the low concentrations of theophylline used suggested that it was acting through adenosine receptor blockade, but its mechanism of action in the latter case is not clear. Theophylline is known to act by at least two other mechanisms: phosphodiesterase inhibition, which raises intracellular cyclic AMP (cAMP) levels, and induction of changes in intracellular calcium levels (19

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“…Additional studies in these models have examined the activity of egg lecithinglycocholic acid mixed micelles (Brajtburg et al 1990), pentoxifylline (oxpentifylline) [Cleary et al 1992;Wasan et al 1990), 1,3-dipropyl-8-(p-sulfophenyl)xanthine (Kaun et al 1990), nifedipine (Gaeta et al 1990), SK&F RDrug Safety 7 (5) 1992 105058 (Brooks et al 1991), Myrj 59 (Tasset et al 1991), diltiazem (Tolins & Raij 1991), theophylline (Heidemann et al 1991), and HW A-448 (Luke et al 1991). The focus on much of this research is to examine the effects of vasoactive agents (i.e.…”

Section: Prevention and Managementmentioning

confidence: 99%

Adverse Drug Reactions to Systemic Antifungals Prevention and Management

1992

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Systemic administration of antifungal agents for invasive mycoses has dramatically increased over the past 10 years in many fields of medicine. The increase has been due both to an increasing immune compromised population and to potent antibacterial agents which allow these fungi to invade tissue. It is apparent that our understanding of the use of both the old and new antifungal agents has significantly increased in the last few years. In this review, we attempt to document our extensive knowledge of the adverse effects of the polyenes, flucytosine, griseofulvin and azoles when given systemically for treatment. Interwoven in this documentation of the adverse reactions to these agents is the attempt to help clinicians potentially avoid some of these adverse effects and if they do occur, to be able to identify and successfully manage them.

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Effect of an adenosine receptor antagonist on acute amphotericin B nephrotoxicity

Cited by 13 publications

References 11 publications

Pentoxifylline modulates activation of human neutrophils by amphotericin B in vitro

Pentoxifylline modulates activation of human neutrophils by amphotericin B in vitro

Mechanisms of amphotericin B-induced decrease in glomerular filtration rate in rats

Adverse Drug Reactions to Systemic Antifungals Prevention and Management

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