Imaging Mass Microscopy of Kidneys from Azithromycin-Treated Rats with Phospholipidosis

Sakurai, Takanobu; Kamio, Kyohei; Sasaki, Kazuhiko; Nishimoto, Tomohiro; Yamaguchi, Junichi; Sasaki, Masahiro; Tsutsumi, Shunsuke

doi:10.1016/j.ajpath.2018.05.018

Cited by 5 publications

(3 citation statements)

References 47 publications

(53 reference statements)

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“…Lastly, azithromycin has shown promise in combination with chloroquine against SARS-CoV-2 (57). This is interesting considering azithromycin's pKa (8.5) and cLogP (2.6) and ability to promote phospholipidosis in vivo (58), which suggests it might also be acting as a CAD in this context. Some COVID-19 patients are responding well to chloroquine whereas others are not.…”

Section: Discussionmentioning

confidence: 98%

Sphingolipid Biosynthesis Inhibition As A Host Strategy Against Diverse Pathogens

Kumar

Park

Hart

et al. 2020

Preprint

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Chloroquine is an anti-malarial and immunosuppressant drug that has cationic amphipathic chemical properties. We performed genome-wide screens in human cells with chloroquine and several other widely used cationic amphipathic drugs (CADs) including the anti-depressants, sertraline (Zoloft) and fluoxetine (Prozac), the analgesic nortriptyline (Pamelor), the anti-arrhythmic amiodarone (Cordarone), and the anti-hypertensive verapamil (Calan) to characterize their molecular similarities and differences. Despite CADs having different disease indications but consistent with them sharing key chemical properties, we found CADs to have remarkably similar phenotypic profiles compared with non-CADs we and others have previously screened (1–5). The most significant genetic interaction for all CADs was the initiating step in sphingolipid biosynthesis catalyzed by serine palmitoyltransferase (SPT). A comparison of genome-wide screens performed with diverse pathogens from viruses, bacteria, plants, and parasites including Ebola (6), adeno-associated virus AAV2 (7), HIV (8), Rotavirus (9), Influenza A (10), Zika virus (11), Picornavirus (12), Exotoxin A (13), Cholera toxin (14), Type III secretion system and Shiga toxin (15, 16), Ricin toxin (17), and Toxoplasma gondii (18) showed SPT as a top common host factor and 80% overlap overall in top hits specifically with CADs. Potential sphingolipid-mediated mechanisms for the host response- and virulence-modulating effects of CADs involve autophagy and SERPINE1/PAI-1 (plasminogen activator inhibitor-1). Chloroquine has recently shown potential as an anti-viral agent for the novel coronavirus SARS-CoV-2, the causative agent of COVID-19 respiratory disease (19, 20). Our study demonstrates that numerous readily available drugs molecularly function highly similar to chloroquine, which suggests they might be considered for further pre-clinical investigation in the context of SARS-CoV-2. More generally, our work suggests the diverse pathogen mitigating potential of drugs that inhibit host sphingolipid biosynthesis such as CADs.Brief SummaryOur study demonstrates that numerous readily available drugs molecularly function highly similar to chloroquine, which suggests they might be considered for further pre-clinical investigation in the context of SARS-CoV-2.

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Section: Discussionmentioning

confidence: 98%

Sphingolipid Biosynthesis Inhibition As A Host Strategy Against Diverse Pathogens

Kumar

Park

Hart

et al. 2020

Preprint

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“…Previous study has shown that Az treatment can result in acute interstitial nephritis and renal failure [ 53 ]. Az accumulation in the kidney correlates with kidney damage as shown by imaging mass microscopy [ 55 ]. Glomerular atrophy, widening of Bowman’s space, and vacuolar degeneration of renal tubular epithelium are the histopathological changes observed in medium to high-dosage groups [ 54 ].…”

Section: Discussionmentioning

confidence: 99%

Pathological and pharmacovigilance monitoring as toxicological imputations of azithromycin and its residues in broilers

Fotouh,

Abdel-Maguid,

Abdelhaseib

et al. 2024

Vet World

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Background and Aim: The importance of monitoring antimicrobial residues in food is underlined by increasing worries about food safety and public health. The potential toxicity of azithromycin (Az) on broilers and its impact on chicken meat residues require further investigation. This study assesses Az’s toxicity effects and associated risks in broiler chickens through evaluation. Materials and Methods: One hundred and twenty chicks were distributed into four equal groups randomly. Each group received different daily oral doses of Az: 200 mg/kg for Az1, 100 mg/kg for Az2, and 50 mg/kg for Az3. The FAz group was given plain water. High-performance liquid chromatography was used to measure Az residue levels in muscle and liver. Oxidative markers (malondialdehyde [MDA], superoxide dismutase [SOD], catalase [CAT]), liver and kidney function tests, and histopathological examination were conducted. Results: The levels of alanine aminotransferase and aspartate aminotransferase increased in Az1 and Az2 groups from 8 h to 3 days and decreased slightly in Az2 by 7 days, while they remained normal in Az3. The levels of uric acid and creatine in the Az1 and Az2 groups increased from 8 h to 3 days and subsequently decreased in Az2 by the 7th day. Az1 group showed the highest increase in MDA levels within 7 days. With higher Az doses, SOD and CAT levels showed a more significant decrease post-treatment. 9.1 μg/kg Az1 liver had the highest residues, whereas none were detected in muscle. Conclusion: At higher doses, Az caused significant liver and kidney damage, whereas lower doses had negligible effects. Muscle tissue contains fewer Az residues than liver. Assessing risks and ensuring compliance with regulations necessitate constant surveillance of Az residues in food. The health implications and risk management insights necessitate further investigation into the long-term effects of Az residues. Keywords: antibiotic residues, azithromycin, broiler chicken, liver functions, oxidative stress.

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“…A heterogeneous group of other pharmaceuticals, namely sertraline [33,34], carbamazepine [35], ranolazine [36], oxymorphone [37], posaconazole [38], viomycin [28], and contrast media [39], have been described as potential causes of renal phospholipidosis when lamellar bodies were found in renal biopsy specimen and no other known causes of phospholipidosis were identified. In addition, certain drugs have been found to induce renal phospholipidosis in rodents and human or mammalian renal cell lines, e.g., antidepressants such as iprindole, imipramine, and clomipramine [40,41] and other pharmaceuticals [42][43][44][45][46][47].…”

Section: Case Reports In Nephrology and Dialysismentioning

confidence: 99%

Hydroxychloroquine-Induced Renal Phospholipidosis: Case Report and Review of Differential Diagnoses

Menke,

Heitplatz,

Van Marck

et al. 2024

Case Rep Nephrol Dial

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Introduction: Renal phospholipidosis describes the accumulation of phospholipids in the lysosomes of kidney cells, in particular podocytes. Originally, this was described primarily in the context of the lysosomal storage disorder Fabry disease. It is now known that a variety of drugs can lead to the accumulation of lysosomal phospholipids. Case Presentation: We present the case of a 69-year-old female patient suffering chronic kidney disease and systemic lupus erythematosus who underwent a kidney biopsy because of a further increase in serum creatinine levels. There was no evidence of lupus nephritis, but electron microscopy showed zebra bodies as a morphological sign of phospholipidosis. This was most likely drug-induced after 25 years of continuous medication with hydroxychloroquine. A renal biopsy 2 years and 6 months earlier, when the renal function of the patient was distinctively better, showed no signs of renal phospholipidosis. Afterward, medication with hydroxychloroquine was discontinued, and renal function parameters remained stable in the 1-year course. Conclusion: This case raises the question of how severely impaired renal function affects the risk of hydroxychloroquine-induced renal phospholipidosis and underlines that hydroxychloroquine should be administered with caution in patients with kidney insufficiency. Moreover, we provide a review of the causes of renal phospholipidosis, which have been described in the literature and give an overview of possible differential diagnoses in cases with histologically proven phospholipidosis in renal biopsies.

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Imaging Mass Microscopy of Kidneys from Azithromycin-Treated Rats with Phospholipidosis

Cited by 5 publications

References 47 publications

Sphingolipid Biosynthesis Inhibition As A Host Strategy Against Diverse Pathogens

Sphingolipid Biosynthesis Inhibition As A Host Strategy Against Diverse Pathogens

Pathological and pharmacovigilance monitoring as toxicological imputations of azithromycin and its residues in broilers

Hydroxychloroquine-Induced Renal Phospholipidosis: Case Report and Review of Differential Diagnoses

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