Mechanistic role of quercetin as inhibitor for adenosine deaminase enzyme in rheumatoid arthritis: systematic review.

Rheumatoid arthritis (RA) is an autoimmune disease involving T and B lymphocytes. Autoantibodies contribute to joint deterioration and worsening symptoms. Adenosine deaminase (ADA), an enzyme in purine metabolism, influences adenosine levels and joint inflammation. Inhibiting ADA could impact RA progression. Intracellular ATP breakdown generates adenosine, which increases in hypoxic and inflammatory conditions. Lymphocytes with ADA play a role in RA. Inhibiting lymphocytic ADA activity has an immune-regulatory effect. Synovial fluid levels of ADA are closely associated with the disease's systemic activity, making it a useful parameter for evaluating joint inflammation. Flavonoids, such as quercetin (QUE), are natural substances that can inhibit ADA activity. QUE demonstrates immune-regulatory effects and restores T-cell homeostasis, making it a promising candidate for RA therapy. In this review, we will explore the impact of QUE in suppressing ADA and reducing produced the inflammation in RA, including preclinical investigations and clinical trials.

Quercetin mitigates rheumatoid arthritis by inhibiting adenosine deaminase in rats.

Rheumatoid arthritis (RA) is a chronic inflammatory joint disease characterized by synovial proliferation and bone destruction. Adenosine deaminase (ADA) is a key inflammatory enzyme that increases joint stiffness and pain in RA. In this study, we evaluated the in-silico, and in vivo inhibitory effect of quercetin isolated from Egyptian Fenugreek on ADA enzyme activity. We also determined the combinatorial effect of quercetin on methotrexate mediated anti-inflammatory efficacy and toxicity. In-silico molecular docking was conducted and confirmed in an in vivo RA rat model. The results showed that the inhibition constant of quercetin on joint ADA by docking and in-vitro was 61.9 and 55.5 mM, respectively. Therefore, quercetin exhibits anti-inflammatory effect in a rat RA model as evidenced by reducing the specific activity of ADA in joint tissues, lower jaw volume, enhance body weight, downregulate ADA gene expression, reduce levels of RA cytokines interleukin-1ß, interleukin-6, tumor necrosis factor-α, also, rheumatoid factor, C-reactive protein, and anti-cyclic citrullinated peptide RA biomarker levels. These findings demonstrate that the purified quercetin has a promising anti-inflammatory effect against RA disease through its inhibitory effects on the ADA enzyme. Furthermore, isolated quercetin improved the anti-inflammatory efficacy of methotrexate, reduced its toxic effects by increasing antioxidant enzymes and reducing oxidative stress.

Evolving Risk of Acute Kidney Injury in COVID-19 Hospitalized Patients: A Single Center Retrospective Study.

Background and Objectives: Within a year, COVID-19 has advanced from an outbreak to a pandemic, spreading rapidly and globally with devastating impact. The pathophysiological link between COVID-19 and acute kidney injury (AKI) is currently being debated among scientists. While some studies have concluded that the mechanisms of AKI in COVID-19 patients are complex and not fully understood, others have claimed that AKI is a rare complication of COVID-19-related disorders. Considering this information gap and its possible influence on COVID-19-associated AKI management, our study aimed to explore the prevalence of AKI and to identify possible risk factors associated with AKI development among COVID-19 hospitalized patients. Materials and Methods: A retrospective cohort study included 83 laboratory-confirmed COVID-19 patients hospitalized at the isolation department in a tertiary hospital in Zagazig City, Egypt between June and August 2020. Patients younger than 18 years of age, those diagnosed with end-stage kidney disease, or those on nephrotoxic medications were excluded. All study participants had a complete blood count, liver and renal function tests, hemostasis parameters examined, inflammatory markers, serum electrolytes, routine urinalysis, arterial blood gas, and non-enhanced chest and abdominal computer tomography (CT) scans. Results: Of the 83 patients, AKI developed in 24 (28.9%) of them, of which 70.8% were in stage 1, 8.3% in stage 2, and 20.8% in stage 3. Patients with AKI were older than patients without AKI, with hypertension and diabetes being the most common comorbidities. Risk factors for AKI include increased age, hypertension, diabetes mellitus, and a higher sequential organ failure assessment (SOFA) score. Conclusions: AKI occurs in a considerable percentage of patients with COVID-19, especially in elderly males, those with hypertension, diabetes, and a higher sequential organ failure assessment (SOFA) score. Hence, the presence of AKI should be taken into account as an important index within the risk spectrum of disease severity for COVID-19 patients.

Therapeutic effect of dimethyl dimethoxy biphenyl dicarboxylate on collagen-induced arthritis in rats.

OBJECTIVE: To study the effect of oral administration of dimethyl dimethoxy biphenyl dicarboxylate (DDB) on adjusting angiogeneic/inflammatory mediators and ameliorating the pathology of bones in rats with collagen-induced arthritis (CIA). METHODS: Wistar rat model of CIA was set up using bovine collagen type II. Fifty rats were divided into five groups randomly: normal, CIA model, DDB treatment, methotrexate (MTX) treatment, and combined DDB+MTX treatment. Ankle joints of rats were imaged with digital X-ray machine to show the destruction of joints. Fore and hind paw and knee joints were removed above the ankle joint then processed for haematoxylin and eosin staining. Plasma levels of vascular endothelial growth factor (VEGF), platelet derived growth factor, interleukin-8 (IL-8), IL-4, tumor necrosis factor α (TNF-α), and cyclooxygenase-2 (COX-2) were quantified by enzyme-linked immunosorbent assay. Nitric oxide levels were detected by Griess reagent. RESULTS: Compared with the CIA model group, a remarkable reduction in various angiogenic (VEGF and IL-8) and inflammatory mediators (TNF-α, IL-4 and COX-2) after treatment with DDB either alone or combined with MTX P<0.05 or P<0.01). Histopathological and X-ray findings were confirmatory to the observed DDB anti-arthritic effect. The DDB-treated group showed amelioration in signs of arthritis which appeared essentially similar to normal. CONCLUSION: Our data shed light on the therapeutic efficacy of DDB in experimental rheumatoid arthritis (RA) compared with a choice drug (MTX) and it may be offered as a second-line drug in the treatment of RA.