Toxicity of amphotericin B emulsion to cultured canine kidney cell monolayers

Lamb, K. A.; Washington, C.; Davis, S.S.; Denyer, Stephen Paul

doi:10.1111/j.2042-7158.1991.tb03529.x

Cited by 15 publications

(8 citation statements)

References 13 publications

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“…For the control of infections with highly virulent C. albicans strains, potent antifungal drugs are required. However, synthesized antifungal chemicals possess generally severe inverse effects, such as impairment of liver and kidney functions (31,47). Therefore, new strategies are required for development of physiologically adapted antifungal agents and combined treatments with multiple kinds of agents.…”

Section: Discussionmentioning

confidence: 99%

Lactoferrin Peptide Increases the Survival of Candida albicans - Inoculated Mice by Upregulating Neutrophil and Macrophage Functions, Especially in Combination with Amphotericin B and Granulocyte-Macrophage Colony-Stimulating Factor

et al. 2001

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To develop a new strategy to control candidiasis, we examined in vivo the anticandidal effects of a synthetic lactoferrin peptide, FKCRRWQWRM (peptide 2) and the peptide that mimics it, FKARRWQWRM (peptide 2). Although all mice that underwent intraperitoneal injection of 5 ؋ 10 8 Candida cells with or without peptide 2 died within 8 or 7 days, respectively, the survival times of mice treated with 5 to 100 g of intravenous peptide 2 per day for 5 days after the candidal inoculation were prolonged between 8.4 ؎ 2.9 and 22.4 ؎ 3.6 days, depending on the dose of peptide 2. The prolongation of survival by peptide 2 was also observed in mice that were infected with 1.0 ؋ 10 9 Candida albicans cells (3.2 ؎ 1.3 days in control mice versus 8.2 ؎ 2.4 days in the mice injected with 10 g of peptide 2 per day). In the high-dose inoculation, a combination of peptide 2 (10 g/day) with amphotericin B (0.1 g/day) and granulocyte-macrophage colony-stimulating factor (GM-CSF) (0.1 g/day) brought prolonged survival. With a combination of these agents, 60% of the mice were alive for more than 22 days. Correspondingly, peptide 2 activated phagocytes inducing inducible NO synthase and the expression of p47 phox and p67 phox , and peptide 2 increased phagocyte Candida-killing activities up to 1.5-fold of the control levels upregulating the generation of superoxide, lactoferrin, and defensin from neutrophils and macrophages. These findings indicated that the anticandidal effects of peptide 2 depend not only on the direct Candida cell growth-inhibitory activity, but also on the phagocytes' upregulatory activity, and that combinations of peptide 2 with GM-CSF and antifungal drugs will help in the development of new strategies for control of candidiasis.

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Section: Discussionmentioning

confidence: 99%

Lactoferrin Peptide Increases the Survival of Candida albicans - Inoculated Mice by Upregulating Neutrophil and Macrophage Functions, Especially in Combination with Amphotericin B and Granulocyte-Macrophage Colony-Stimulating Factor

et al. 2001

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“…A mistura de AB-DOC com emulsão para nutrição parenteral Intralipid® 20% (AB-DOC-IL) reduziu a toxicidade de AB in vitro sobre eritrócitos (Kirsh et al, 1988), células tubulares renais de cães (Lamb, Washington, Davis, 1990) e coelhos (Joly et al, 1994). O dano renal in vivo demonstrou a possibilidade de administrar doses superiores àquelas usadas com AB-DOC, permitindo que a dose máxima tolerada para camundongos fosse nove vezes maior com AB-DOC-IL (Kirsh et al, 1988), embora outro estudo tenha obtido valores inferiores (de 1,7 a 2,5 vezes) (Joly et al, 1994).…”

Section: Estudos In Vitro E Em Animaisunclassified

Eficiência terapêutica das formulações lipídicas de anfotericina B

Filippin

Souza

2006

Rev. Bras. Cienc. Farm.

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“…Therefore, with the discovery that AmB incorporated into liposome or lipid complexes was less toxic to animals than was Fungizone but at the same time was equally therapeutic (134), experiments were designed to compare various toxic and antifungal activities of AmB alone and ABLC in vitro. Studies on carrier effects were extended to detergents other than deoxycholate (82,165,179) and to various lipids added to AmB-cell suspensions, e.g., lipoproteins (22), triglycerides (172), preformed phospholipid vesicles (190,191), preformed mixed micelles of egg lecithin and glycocholate (32), and lecithin-stabilized triglyceride emulsions (117). The techniques used for measuring damage in these in vitro assays can be grouped into short-and long-term assays (101).…”

Section: Damage To Mammalian and Fungal Cellsmentioning

confidence: 99%

Carrier effects on biological activity of amphotericin B

1996

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Amphotericin B (AmB), the drug of choice for the treatment of most systemic fungal infections, is marketed under the trademark Fungizone, as an AmB-deoxycholate complex suitable for intravenous administration. The association between AmB and deoxycholate is relatively weak; therefore, dissociation occurs in the blood. The drug itself interacts with both mammalian and fungal cell membranes to damage cells, but the greater susceptibility of fungal cells to its effects forms the basis for its clinical usefulness. The ability of the drug to form stable complexes with lipids has allowed the development of new formulations of AmB based on this property. Several lipid-based formulations of the drug which are more selective in damaging fungal or parasitic cells than mammalian cells and some of which also have a better therapeutic index than Fungizone have been developed. In vitro investigations have led to the conclusion that the increase in selectivity observed is due to the selective transfer of AmB from lipid complexes to fungal cells or to the higher thermodynamic stability of lipid formulations. Association with lipids modulates AmB binding to lipoproteins in vivo, thus influencing tissue distribution and toxicity. For example, lipid complexes of AmB can be internalized by macrophages, and the macrophages then serve as a reservoir for the drug. Furthermore, stable AmB-lipid complexes are much less toxic to the host than Fungizone and can therefore be administered in higher doses. Experimentally, the efficacy of AmB-lipid formulations compared with Fungizone depends on the animal model used. Improved therapeutic indices for AmB-lipid formations have been demonstrated in clinical trials, but the definitive trials leading to the selection of an optimal formulation and therapeutic regimen have not been done.

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Toxicity of amphotericin B emulsion to cultured canine kidney cell monolayers

Cited by 15 publications

References 13 publications

Lactoferrin Peptide Increases the Survival of Candida albicans - Inoculated Mice by Upregulating Neutrophil and Macrophage Functions, Especially in Combination with Amphotericin B and Granulocyte-Macrophage Colony-Stimulating Factor

Lactoferrin Peptide Increases the Survival of Candida albicans - Inoculated Mice by Upregulating Neutrophil and Macrophage Functions, Especially in Combination with Amphotericin B and Granulocyte-Macrophage Colony-Stimulating Factor

Eficiência terapêutica das formulações lipídicas de anfotericina B

Carrier effects on biological activity of amphotericin B

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