Advanced Oxidation Protein Product Promotes Oxidative Accentuation in Renal Epithelial Cells via the Soluble (Pro)renin Receptor-Mediated Intrarenal Renin-Angiotensin System and Nox4-H2O2 Signaling

Full-length (pro)renin receptor (fPRR), a research hotspot of the renin-angiotensin system (RAS), plays a serious role in kidney injury. However, the relationship between fPRR and advanced oxidation protein product (AOPP) remains largely unexplored. This study was aimed at exploring the effect of fPRR, especially its 28 kDa soluble form called soluble PRR (sPRR), in AOPP-induced oxidative stress in HK-2 cells, a renal proximal tubular epithelial cell line. Incubation of HK-2 cells with 100 μg/ml AOPP resulted in significant upregulation of fPRR expression and caused an approximately fourfold increase in medium sPRR secretion. However, unmodified albumin did not demonstrate the same effects under the same concentration. Treatment of HK-2 cells with the site-1 protease (S1P) inhibitor PF429242 (40 μM) or S1P siRNA significantly inhibited AOPP-induced sPRR generation. fPRR decoy inhibitor PRO20 and PF429242 treatment for 24 h remarkably attenuated the AOPP-induced upregulation of RAS components. Furthermore, PF429242 significantly reduced the AOPP-stimulated expression of NADPH oxidase 4 (Nox4) and H2O2 expression. The use of a small recombinant protein, named sPRR-His, reversed these alterations. In conclusion, these results provided the first demonstration of AOPP-promoted activation of sPRR. Increased renal proximal tubule Nox4-derived H2O2 contributed to the aggravation of oxidative stress. Targeting S1P-derived sPRR is a promising intervention strategy for chronic kidney disease.

Association of Low Molecular Weight Plasma Aminothiols with the Severity of Coronavirus Disease 2019

Objective. Aminothiols (glutathione (GSH), cysteinylglycine (CG)) may play an important role in the pathogenesis of coronavirus disease 2019 (COVID-19), but the possible association of these indicators with the severity of COVID-19 has not yet been investigated. Methods. The total content ( t ) and reduced forms ( r ) of aminothiols were determined in patients with COVID-19 ( n = 59 ) on admission. Lung injury was characterized by computed tomography (CT) findings in accordance with the CT0-4 classification. Results. Low tGSH level was associated with the risk of severe COVID-19 ( tGSH ≤ 1.5 μ M , mild vs. moderate/severe: risk ratio RR = 3.09 , p = 0.007 ) and degree of lung damage ( tGSH ≤ 1.8 μ M , CT < 2 vs. CT ≥ 2 : RR = 2.14 , p = 0.0094 ). The rGSH level showed a negative association with D-dimer levels ( ρ = − 0.599 , p = 0.014 ). Low rCG level was also associated with the risk of lung damage ( rCG ≤ 1.3 μ M , CT < 2 vs. CT ≥ 2 : RR = 2.28 , p = 0.001 ). Levels of rCG ( ρ = − 0.339 , p = 0.012 ) and especially tCG ( ρ = − 0.551 , p = 0.004 ) were negatively associated with platelet count. In addition, a significant relationship was found between the advanced oxidation protein product level and tGSH in patients with moderate or severe but not in patients with mild COVID-19. Conclusion. Thus, tGSH and rCG can be seen as potential markers for the risk of severe COVID-19. GSH appears to be an important factor to oxidative damage prevention as infection progresses. This suggests the potential clinical efficacy of correcting glutathione metabolism as an adjunct therapy for COVID-19.

Association of advanced oxidation protein product, thiobarbituric acid reactive substances and total sulfhydryl groups with retinal blood vessels caliber

Introduction/Objective. Intensive oxidative stress is proven in patients with diabetes mellitus and important in the development of a microvascular complication of type 2 diabetes mellitus. The aim of the study was to investigate the relationship between morphometric parameters of retinal blood vessels in patients with diabetic retinopathy (DR) and the levels of parameters of oxidative stress: advanced oxidation protein product (AOPP), thiobarbituric acid reactive substances (TBARS), and total sulfhydryl (SH) groups in blood samples. Methods. The patients (the group with DR and controls) were sex- and age-matched. Glycaemia, hemoglobin A1C HbA1C, total cholesterol and its fractions, and triglycerides were measured in blood samples. AOPP and total SH groups were determined in the plasma by specific methods. Modification of the thiobarbituric acid method was used for the determination of TBARS. The number and diameter of retinal blood vessels, as morphometric parameters on digital retinal photography, was determined by using the ImageJ software. Student?s t-test was used as the statistical method for the evaluation of differences between the morphometric and blood test parameters. The significance of differences in morphometric parameters of retinal blood was establish by one-way ANOVA. Results. Significantly higher levels of parameters of oxidative stress (AOPP and TBARS) were in the group of patients with DR than in the controls. This difference was also present among the patients with mild and severe forms of DR (AOPP F 77.03, p < 0.001) (TBARS F 63.28, p < 0.001). The diameter of retinal blood vessels correlated with levels of AOPP, but only in patients with mild DR. Conclusion. Parameters of oxidative stress, AOPP and TBARS, may be important for the follow-up of DR. In early stages in diabetic retinopathy, AOPP can be a valuable biomarker.

PENGARUH LAMA PAPARAN ASAP TERHADAP RISIKO ATEROSKLEROSIS MELALUI PENGUKURAN MALONILDEALDEHYDE DAN ADVANCED OXIDATION PROTEIN PRODUCT SECARA INVIVO

Penyakit kardiovaskuler menjadi masalah kesehatan di dunia dan di Indonesia. Aterosklerosis diramalkan tahun 2020 merupakan penyebab utama morbiditas dan mortalitas di masyarakat. Radikal bebas mampu secara langsung dan tidak langsung menginduksi stress oksidatif didalam tubuh. Radikal bebas dapat menyerang asam lemak tak jenuh ganda (PUFA), yang akan terputus menjadi sederhana sala satunya malonyldealdehide (MDA). AOPP (Advanced Oxidation Protein Product) berasal sebagai akibat dari tindakan radikal bebas pada protein dan sebagai mediator inflamasi. Masalah penelitian adalah apakah ada pengaruh lama paparan asap terhadap risiko aterosklerosismelalui pengukuran MDA dan AOPP secara invivo. Mengetahui pengaruh lama paparan asap terhadap risiko aterosklerosis melalui pengukuran MDA dan AOPP secara invivo. Jenis penelitian ini yakni penelitian true experimental dengan menggunakan post-test only control group design. Populasi penelitian ini adalah tikus Rattus Novergicus jantan, strain wistar dengan umur 11-12 minggu dengan berat badan ±200-210 gram, sedangkan pengambilan sampel ditetapkan berdasarkan kriteria inklusi dan eksklusi. Variabel penelitian adalah lama paparan 7 jam, lama paparan 9 jam, MDA, dan AOPP. Instrumen yang digunakan dalam penelitian ini adalah pemeriksaan laboratorium pada MDA dan AOPP. Pada analisis deskriptif, variabel MDA didapatkan rerata kelompok kontrol (0,239±0,003), kelompok paparan 7 jam (0,241±0,005), dan kelompok paparan 9 jam (0,258±0,000). Pada variabel AOPP didapatkan rerata kelompok kontrol (15,207±3,222), kelompok paparan 7 jam (37,546±10,528), dan kelompok paparan 9 jam (59,573±14,929). Uji normalitas data menunjukkan data berdistribusi normal (p-value MDA (0,076) dan AOPP (0,346)), uji homogenitas menunjukkan data tidak homogen (p-value MDA (0,001) dan AOPP (0,004)). Tidak ada pengaruh kadar MDA antara kelompok kontrol (p-value= 0,292) dengan kelompok paparan 7 jam, ada pengaruh kadar MDA antara kelompok kontrol (p-value= 0,0001) dengan kelompok paparan 9 jam, ada pengaruh kadar MDA antara kelompok paparan 7 jam (p-value= 0,0001) dengan kelompok paparan 9 jam, ada pengaruh kadar AOPP antara kelompok kontrol (p-value= 0,0001) dengan kelompok paparan 7 jam, ada pengaruh kadar AOPP antara kelompok kontrol (p-value= 0,0001) dengan kelompok paparan 9 jam, ada pengaruh kadar AOPP antara kelompok paparan 7 jam (p-value= 0,0001) dengan kelompok paparan 9 jam. Tidak ada pengaruh kadar MDA kelompok kontrol dengan kelompok paparan 7 jam. ada pengaruh kadar MDA kelompok kontrol dengan kelopok paparan 9 jam, antara kelompok paparan 7 jam dan 9 jam, kadar AOPP kelompok kontrol dengan paparan 7 jam, kelompok kontrol dengan paparan 9 jam, dan antara kelompok paparan 7 jam dan 9 jam. Mempertimbangkan hasil penelitian, MDA merupakan senyawa yang dapat menggambarkan aktivitas radikal bebas di dalam sel, dan AOPP merupakan produk kerusakan oksidatif pada protein, sebagai salah satu petunjuk terjadinya stress oksidatif radikal bebas.

Penconazole alters redox status, cholinergic function, and membrane-bound ATPases in the cerebrum and cerebellum of adult rats

Pesticides exposure causes usually harmful effects to the environment and human health. The present study aimed to investigate the potential toxic effects of penconazole, a triazole fungicide, on the cerebrum and cerebellum of adult rats. Penconazole was administered intraperitoneally to male Wistar rats at a dose of 67 mg kg−1 body weight every 2 days during 9 days. Results showed that penconazole induced oxidative stress in rat cerebrum and cerebellum tissues. In fact, we have found a significant increase in malondialdehyde, hydrogen peroxide, and advanced oxidation protein product levels, as well as an alteration of the antioxidant status, enzymatic (superoxide dismutase and catalase) and nonenzymatic (glutathione), the cholinergic function, and membrane-bound ATPases (Na+/K+-ATPase and Mg2+-ATPase). Penconazole also provoked histological alterations marked by pyknotic and vacuolated neurons in the cerebrum and apoptosis and edema in the cerebellum Purkinje cells’ layer. Therefore, the use of this neurotoxicant fungicide must be regularly monitored in the environment.

Oral Exposure to Atrazine Induces Oxidative Stress and Calcium Homeostasis Disruption in Spleen of Mice

The widely used herbicide atrazine (ATR) can cause many adverse effects including immunotoxicity, but the underlying mechanisms are not fully understood. The current study investigated the role of oxidative stress and calcium homeostasis in ATR-induced immunotoxicity in mice. ATR at doses of 0, 100, 200, or 400 mg/kg body weight was administered to Balb/c mice daily for 21 days by oral gavage. The studies performed 24 hr after the final exposure showed that ATR could induce the generation of reactive oxygen species in the spleen of the mice, increase the level of advanced oxidation protein product (AOPP) in the host serum, and cause the depletion of reduced glutathione in the serum, each in a dose-related manner. In addition, DNA damage was observed in isolated splenocytes as evidenced by increase in DNA comet tail formation. ATR exposure also caused increases in intracellular Ca2+within splenocytes. Moreover, ATR treatment led to increased expression of genes for some antioxidant enzymes, such asHO-1andGpx1, as well as increased expression of NF-κB and Ref-1 proteins in the spleen. In conclusion, it appears that oxidative stress and disruptions in calcium homeostasis might play an important role in the induction of immunotoxicity in mice by ATR.