Human Toxicity of Ibuprofen

Volans, Glyn

doi:10.1002/9781118743614.ch12

Cited by 4 publications

(1 citation statement)

References 57 publications

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“…However, the literature documents that ibuprofen is more rapidly metabolized in plasma than aspirin (18). Importantly, patients who are known to have overdosed on ibuprofen (in one case, the patient consumed more than 20 times the peak plasma concentration seen after a single dose of 400 mg ibuprofen [17,19]) are reported to have experienced no to mild symptoms without experiencing sequelae (17,20). All subsequent tests were performed on C. neoformans strain LMPE 046, as this strain showed the greatest sensitivity toward all test drugs, including fluconazole and amphotericin B (see Tables S1 and S2 in the supplemental material).…”

Section: Resultsmentioning

confidence: 99%

Repurposing of Aspirin and Ibuprofen as Candidate Anti-Cryptococcus Drugs

Ogundeji

Pohl

Sebolai

2016

Antimicrob Agents Chemother

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The usage of fluconazole and amphotericin B in clinical settings is often limited by, among other things, drug resistance development and undesired side effects. Thus, there is a constant need to find new drugs to better manage fungal infections. Toward this end, the study described in this paper considered the repurposing of aspirin (acetylsalicylic acid) and ibuprofen as alternative drugs to control the growth of cryptococcal cells. In vitro susceptibility tests, including a checkerboard assay, were performed to assess the response of Cryptococcus neoformans and Cryptococcus gattii to the above-mentioned anti-inflammatory drugs. Next, the capacity of these two drugs to induce stress as well as their mode of action in the killing of cryptococcal cells was determined. The studied fungal strains revealed a response to both aspirin and ibuprofen that was dose dependent, with ibuprofen exerting greater antimicrobial action. More importantly, the MICs of these drugs did not negatively (i) affect growth or (ii) impair the functioning of macrophages; rather, they enhanced the ability of these immune cells to phagocytose cryptococcal cells. Ibuprofen was also shown to act in synergy with fluconazole and amphotericin B. The treatment of cryptococcal cells with aspirin or ibuprofen led to stress induction via activation of the high-osmolarity glycerol (HOG) pathway, and cell death was eventually achieved through reactive oxygen species (ROS)-mediated membrane damage. The presented data highlight the potential clinical application of aspirin and ibuprofen as candidate anti-Cryptococcus drugs.T he advent of HIV/AIDS has led to the emergence of species such as Cryptococcus neoformans and Cryptococcus gattii as important disease-causing microbes (1-3). To demonstrate this point, these species are reported to cause over 1 million infections worldwide, with the highest burden of infections being localized in resource-poor settings (4). In their paper, Perfect et al. argued that the management of fungal diseases is strongly dependent on capital resources available to a specific region (5). Based on the latter, Sebolai and Ogundeji further argued that it is not surprising for countries in sub-Saharan Africa, given the complex geopolitical and socioeconomic challenges that prevail in this region, to be unable to provide the necessary life-saving drugs, which are often expensive (6). Toward this end, a solution may be to repurpose already FDA-approved drugs that are cheap, such as aspirin (acetylsalicylic acid) and ibuprofen.We have previously reported that aspirin affected Cryptococcus cells in a number of ways: it (i) decreased capsule shedding, (ii) inhibited the production and trafficking of capsule-associated 3-hydroxy fatty acids, and (iii) inhibited cellular growth (7). In the current study, we build further on our prior antimicrobial work by drawing a comparison between the effects of aspirin and ibuprofen. Importantly, we also attempt to elucidate the mode of action employed by the two drugs in the killing of cryptococcal...

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