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      Quercetin Attenuates Pancreatic and Renal D-Galactose-Induced Aging-Related Oxidative Alterations in Rats

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          Abstract

          Aging is an oxidative stress-associated process that progresses with age. Our aim is to delay or attenuate these oxidative alterations and to keep individuals healthy as they age using natural compounds supplementation. Therefore, we conducted the present study to investigate the protective potentials of quercetin against D-galactose (D-gal)-associated oxidative alterations that were induced experimentally in male Wistar rats. Forty-five rats were randomly allocated into five groups of nine rats each. The groups were a control group that was reared on a basal diet and injected subcutaneously with 120 mg D-gal dissolved in physiological saline solution (0.9% NaCl) per kg body weight daily and quercetin-treated groups that received the same basal diet and subcutaneous daily D-gal injections were supplemented orally with 25, 50, and 100 mg of quercetin per kg body weight for 42 days. Pancreatic and renal samples were subjected to histopathological, immunohistochemical, and relative mRNA expression assessments. Aging ( p53, p21, IL-6, and IL-8), apoptotic ( Bax, CASP-3, and caspase-3 protein), proliferative (Ki67 protein), antiapoptotic ( Bcl2 and Bcl2 protein), inflammatory ( NF-κB, IL-1β, and TNF-α), antioxidant ( SOD1), and functional markers ( GCLC and GCLM genes and insulin, glucagon, and podocin proteins) were determined to evaluate the oxidative alterations induced by D-gal and the protective role of quercetin. D-gal caused oxidative alterations of the pancreas and kidneys observed via upregulations of aging, apoptotic, and inflammatory markers and downregulated the antiapoptotic, proliferative, antioxidant, and functional markers. Quercetin potentially attenuated these aging-related oxidative alterations in a dose-dependent manner. Finally, we can conclude that quercetin supplementation is considered as a promising natural protective compound that could be used to delay the aging process and to maintain human health.

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          Antioxidant Activities of Quercetin and Its Complexes for Medicinal Application

          Quercetin is a bioactive compound that is widely used in botanical medicine and traditional Chinese medicine due to its potent antioxidant activity. In recent years, antioxidant activities of quercetin have been studied extensively, including its effects on glutathione (GSH), enzymatic activity, signal transduction pathways, and reactive oxygen species (ROS) caused by environmental and toxicological factors. Chemical studies on quercetin have mainly focused on the antioxidant activity of its metal ion complexes and complex ions. In this review, we highlight the recent advances in the antioxidant activities, chemical research, and medicinal application of quercetin.
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            Bioavailability of Quercetin in Humans with a Focus on Interindividual Variation

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              Podocin localizes in the kidney to the slit diaphragm area.

              We recently cloned a novel gene, NPHS2, involved in autosomal recessive steroid-resistant nephrotic syndrome. This gene encodes a novel podocyte protein, podocin. Given its similarity with the stomatin family proteins, podocin is predicted to be an integral membrane protein with a single membrane domain forming a hairpin-like structure placing both N- and C-termini in the cytosol. Here, we show by in situ hybridization, that during development, the NPHS2 transcript is first expressed in mesonephric podocytes from the S-shaped body and, later, in the metanephric kidney, in the future podocytes at the late S-shaped body stage. In the mature kidney, NPHS2 is exclusively expressed in the podocytes of mature glomeruli. We generated rabbit polyclonal antibodies against fusion proteins derived from the N- and the C-terminal regions of podocin which detected a single band of 49-kd in transfected HEK293 cell lysates by immunoprecipitation and Western blotting. By immunohistology, podocin was detected in podocytes from the early capillary loop stage in the developing nephrons, and at the basal pole, along the GBM, in mature glomeruli. By electron microscopy, we demonstrate that podocin is facing the slit diaphragm with its two ends in the cytoplasm of the foot processes, in agreement with its predicted structure. Our results suggest that podocin could serve to anchor directly or indirectly components of the slit diaphragm to the cytoskeleton.
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                Author and article information

                Journal
                Int J Mol Sci
                Int J Mol Sci
                ijms
                International Journal of Molecular Sciences
                MDPI
                1422-0067
                18 June 2020
                June 2020
                : 21
                : 12
                : 4348
                Affiliations
                [1 ]Department of Biochemistry, Faculty of Veterinary Medicine, Damanhour University, Damanhour 22511, Egypt
                [2 ]Biochemistry Department, Faculty of Veterinary Medicine, Alexandria University, Alexandria 22758, Egypt; lebdam1979@ 123456alexu.edu.eg (M.A.L.); elfeky@ 123456alexu.edu.eg (M.E.)
                [3 ]Histology and Cytology Department, Faculty of Veterinary Medicine, Damanhour University, Damanhour 22511, Egypt; ahmed.elsayed@ 123456damanhour.edu.eg
                [4 ]Department of Physiology, Faculty of Veterinary Medicine, Kafrelsheikh University, Kafrelsheikh 33516, Egypt; mostafa.ataa@ 123456vet.kfs.edu.eg
                [5 ]Histology and Cytology Department, Faculty of Veterinary Medicine, Zagazig University, Zagazig 44519, Egypt; y-elewa@ 123456vetmed.hokudai.ac.jp
                [6 ]Laboratory of Anatomy, Faculty of Veterinary Medicine, Basic Veterinary Sciences, Hokkaido University, Sapporo 060-0818, Japan
                [7 ]Pharmaceutical Research Institute, Albany College of Pharmacy and Health Sciences, Rensselaer, NY 12144, USA
                Author notes
                Author information
                https://orcid.org/0000-0001-9721-4360
                https://orcid.org/0000-0002-8344-0807
                https://orcid.org/0000-0003-2722-2466
                https://orcid.org/0000-0002-9294-015X
                Article
                ijms-21-04348
                10.3390/ijms21124348
                7352460
                32570962
                91d285cf-09b8-4383-ac0b-8b7e909920ef
                © 2020 by the authors.

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                : 22 May 2020
                : 15 June 2020
                Categories
                Article

                Molecular biology
                aging,d-galactose,oxidative stress,quercetin,antiaging
                Molecular biology
                aging, d-galactose, oxidative stress, quercetin, antiaging

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