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      Nephritic cell damage and antioxidant status in rats exposed to leachate from battery recycling industry

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          Abstract

          Limited studies have assessed the toxic effect of sub-acute and sub-chronic exposure of leachate (mixture of metals) in mammalian kidney. The sub-acute and sub-chronic exposure of mature male Wistar-strain albino rats (200–220 g) were given by oral administration with leachate from Elewi Odo municipal battery recycling industry (EOMABRIL) for period of 7 and 60 days respectively, at different concentrations (20%, 40%, 60%, 80% and 100%). This was to evaluate its toxic effects on male renal functions using biomarkers of oxidative stress and nephro-cellular damage. Control groups were treated equally, but given distilled water instead of the leachate. All the groups were fed with the same standard food and had free access to drinking water. Following the exposure, results showed that the treatment induced systemic toxicity at the doses tested by causing a significant ( p<0.05) alteration in enzymatic antioxidants-catalase (CAT) and superoxide dismutase (SOD) in the kidneys which resulted into elevated levels of malonaldehyde (MDA). Reduced glutathione (GSH) levels were found to be significantly ( p<0.05) depleted relative to the control group. Considerable renal cortical congestion and numerous tubules with protein casts were observed in the lumen of EOMABRIL-treated rats. These findings conclude that possible mechanism by which EOMABRIL at the investigated concentrations elicits nephrotoxicity could be linked to the individual, additive, synergistic or antagonistic interactions of this mixture of metals with the renal bio-molecules, alteration of kidney detoxifying enzymes and necrosis of nephritic tubular epithelial cells.

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          PROTEIN MEASUREMENT WITH THE FOLIN PHENOL REAGENT

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            A glimpse of various pathogenetic mechanisms of diabetic nephropathy.

            Diabetic nephropathy is a well-known complication of diabetes and is a leading cause of chronic renal failure in the Western world. It is characterized by the accumulation of extracellular matrix in the glomerular and tubulointerstitial compartments and by the thickening and hyalinization of intrarenal vasculature. The various cellular events and signaling pathways activated during diabetic nephropathy may be similar in different cell types. Such cellular events include excessive channeling of glucose intermediaries into various metabolic pathways with generation of advanced glycation products, activation of protein kinase C, increased expression of transforming growth factor β and GTP-binding proteins, and generation of reactive oxygen species. In addition to these metabolic and biochemical derangements, changes in the intraglomerular hemodynamics, modulated in part by local activation of the renin-angiotensin system, compound the hyperglycemia-induced injury. Events involving various intersecting pathways occur in most cell types of the kidney.
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              Resveratrol protects diabetic kidney by attenuating hyperglycemia-mediated oxidative stress and renal inflammatory cytokines via Nrf2-Keap1 signaling.

              Hyperglycemia-mediated oxidative stress plays a crucial role in the progression of diabetic nephropathy. Hence, the present study was hypothesized to explore the renoprotective nature of resveratrol by assessing markers of oxidative stress, proinflammatory cytokines and antioxidant competence in streptozotocin-nicotinamide-induced diabetic rats. Oral administration of resveratrol to diabetic rats showed a significant normalization on the levels of creatinine clearance, plasma adiponectin, C-peptide and renal superoxide anion, hydroxyl radical, nitric oxide, TNF-α, IL-1β, IL-6 and NF-κB p65 subunit and activities of renal aspartate transaminase, alanine transaminase and alkaline phosphatase in comparison with diabetic rats. The altered activities of renal aldose reductase, sorbitol dehydrogenase and glyoxalase-I and elevated level of serum advanced glycation end products in diabetic rats were also reverted back to near normalcy. Further, resveratrol treatment revealed a significant improvement in superoxide dismutase, catalase, glutathione peroxidase, glutathione-S-transferase and glutathione reductase activities and vitamins C and E, and reduced glutathione levels, with a significant decline in lipid peroxides, hydroperoxides and protein carbonyls levels in diabetic kidneys. Similarly, mRNA and protein analyses substantiated that resveratrol treatment notably normalizes the renal expression of Nrf2/Keap1and its downstream regulatory proteins in the diabetic group of rats. Histological and ultrastructural observations also evidenced that resveratrol effectively protects the kidneys from hyperglycemia-mediated oxidative damage. These findings demonstrated the renoprotective nature of resveratrol by attenuating markers of oxidative stress in renal tissues of diabetic rats. Copyright © 2011 Elsevier B.V. All rights reserved.
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                Author and article information

                Journal
                Interdiscip Toxicol
                Interdiscip Toxicol
                ITX
                Interdisciplinary Toxicology
                Slovak Toxicology Society SETOX
                1337-6853
                1337-9569
                March 2016
                17 May 2017
                : 9
                : 1
                : 1-11
                Affiliations
                [1 ]Toxicology and Safety Unit, Department of Environmental Health Sciences, Faculty of Public Health, College of Medicine, University of Ibadan, Ibadan, Nigeria
                [2 ]Functional Foods, Nutraceuticals and Phytomedicine Research Laboratory, Department of Biochemistry, Federal University of Technology, Akure, Nigeria
                Author notes
                Correspondence address: Jacob K. Akintunde, Toxicology and Safety Unit, Department of Environmental Health Sciences, Faculty of Public Health, College of Medicine, University of Ibadan, Ibadan, Nigeria. FAX +23408064156056. E-MAIL: akintundejacob@ 123456yahoo.com
                Article
                ITX-9-1
                10.1515/intox-2016-0001
                5458108
                a08e6139-ad07-459d-9639-1ec44d31f279
                Copyright © 2016 SETOX & Institute of Experimental Pharmacology and Toxicology, SASc.

                This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 License. (CC BY-NC-ND 4.0)

                History
                : 08 September 2015
                : 05 March 2016
                : 07 March 2016
                Categories
                Original Article

                Toxicology
                eomabril,antioxidant status,sub-acute,sub-chronic,interactions,nephrosis
                Toxicology
                eomabril, antioxidant status, sub-acute, sub-chronic, interactions, nephrosis

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