Bacterial quality of urinary tract in patients with alkaptonuria

Al-Tarawneh, Amjad; Al-limoun, Muhamad O.; Khlaifat, Ali M; Tarawneh, Ibrahim N.; Mwafi, Nesrin; Khleifat, Khaled M.; Alqaraleh, Moath; Mizher, Hussam

doi:10.1016/j.amjms.2022.12.028

Cited by 2 publications

(2 citation statements)

References 17 publications

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“…This HGA secreted in the urine is not only obtained from the glomerular filtration but a major percentage of HGA urine is obtained from the renal tubular secretion [ 28 ]. In addition to HGA in urine, the bacterial load of urine of infected male patients is also 2–3 times greater than female AKU patients [ 29 ]. Moreover, it can be confirmed by the genetic analysis for mutations in HGD gene.…”

Section: Introductionmentioning

confidence: 99%

Identification of Potential Inhibitors for the Treatment of Alkaptonuria Using an Integrated In Silico Computational Strategy

et al. 2023

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Alkaptonuria (AKU) is a rare genetic autosomal recessive disorder characterized by elevated serum levels of homogentisic acid (HGA). In this disease, tyrosine metabolism is interrupted because of the alterations in homogentisate dioxygenase (HGD) gene. The patient suffers from ochronosis, fractures, and tendon ruptures. To date, no medicine has been approved for the treatment of AKU. However, physiotherapy and strong painkillers are administered to help mitigate the condition. Recently, nitisinone, an FDA-approved drug for type 1 tyrosinemia, has been given to AKU patients in some countries and has shown encouraging results in reducing the disease progression. However, this drug is not the targeted treatment for AKU, and causes keratopathy. Therefore, the foremost aim of this study is the identification of potent and druggable inhibitors of AKU with no or minimal side effects by targeting 4-hydroxyphenylpyruvate dioxygenase. To achieve our goal, we have performed computational modelling using BioSolveIT suit. The library of ligands for molecular docking was acquired by fragment replacement of reference molecules by ReCore. Subsequently, the hits were screened on the basis of estimated affinities, and their pharmacokinetic properties were evaluated using SwissADME. Afterward, the interactions between target and ligands were investigated using Discovery Studio. Ultimately, compounds c and f were identified as potent inhibitors of 4-hydroxyphenylpyruvate dioxygenase.

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Section: Introductionmentioning

confidence: 99%

Identification of Potential Inhibitors for the Treatment of Alkaptonuria Using an Integrated In Silico Computational Strategy

et al. 2023

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“…As a general rule, the disease is suspected in the presence of the triad of: brownish-black turning of urine if left standing or upon alkalinization, ochronosis and extensive degenerative changes and arthritis in the large joints and spine of young adults (Raina et al, 2008;Doganavsargilet al, 2015;Gil et al, 2016). In later stages of the disease, AKU patients complain of recurrent kidney stones formation with the function of kidneys being conserved (Wolff et al, 2015 ;Al-Tarawneh et al, 2023).Few studies reported the chemical composition of AKUrenal calculi and the analysis of stones with efficient physical methods such as ICP-MS are poorly documented in the literature. The aim of this study is to investigate the composition of renal stones collected from AKU patient and compare them with renal stones obtained from non-AKU patient.…”

Section: Introductionmentioning

confidence: 99%

Renal Calculi Composition in Alkaptonuria: Insights on Etiology

2023

JJBS

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Alkaptonuria is a rare genetic disease caused by defect in the phenylalanine and tyrosine metabolism due to a deficiency in homogentisate 1,2-dioxygenase enzyme. The formation of ochronotic brownish-black pigment is the hallmark of the disease and at later stage AKU patients complain of recurrent renal calculi formation. In this report, we describe the case of 48 years old man who is previously diagnosed with alkaptonuria and is suffering from recurrent renal stones formation. We analysed the chemical composition of his AKU-stones by Fourier transform infrared spectroscopy (FTIR) and Inductively coupled plasma-mass spectrometry (ICP-MS) respectively and compared them with non-AKU stones obtained from 48 years old non-AKU man. Our results showed that sulphur content was 33 folds higher in AKU stones compared to non-AKU sample. This provides an evidence that sulphur-rich protein is a critical component for stone formation and growth from calcium oxalate monohydrate (COM) crystals. Accordingly, a model was proposed for the formation and growth of ochronotic renal stones in AKU patients with protein stimulated COM aggregation based on the generation of adducts between benzoquinone acetate and sulphur-rich proteins. Overall, the outcomes of this study shed a new light on the disease pathogenesis at the molecular level and opened new perspective which might orient the physicians to find a convenient therapeutic intervention or at least prophylactic measures to avoid recurrent formation of calculi in AKU patients.

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Bacterial quality of urinary tract in patients with alkaptonuria

Cited by 2 publications

References 17 publications

Identification of Potential Inhibitors for the Treatment of Alkaptonuria Using an Integrated In Silico Computational Strategy

Identification of Potential Inhibitors for the Treatment of Alkaptonuria Using an Integrated In Silico Computational Strategy

Renal Calculi Composition in Alkaptonuria: Insights on Etiology

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