Enofovir for 2? years [6]. Tubular dysfunction may precede the decline of renalEnofovir for 2?

Enofovir for 2? years [6]. Tubular dysfunction may precede the decline of renal
Enofovir for 2? years [6]. Tubular dysfunction may precede the decline of renal function [7]. The main site of TDF toxicity is the proximal tubule, and in severe PubMed ID:https://www.ncbi.nlm.nih.gov/pubmed/26080418 cases, patients can develop Fanconi syndrome (which is characterized by phosphaturia, glycosuria, bicarbonate wasting , tubular proteinuria, and aminoaciduria,) or acute kidney injury [7]. Several case?2013 Abraham et al.; licensee BioMed Central Ltd. This is an Open Access Crotaline mechanism of action article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.Abraham et al. Journal of Biomedical Science 2013, 20:61 http://www.jbiomedsci.com/content/20/1/Page 2 ofreports, observational studies, and animal models, support the view that tenofovir is a proximal tubular toxin [8-10]. Current evidence suggests that mitochondria are the subcellular target organelles of tenofovir. Several human and animal studies have shown damage to specifically renal proximal tubular mitochondria [11-13]. In the TDF treated HIV patients who underwent kidney biopsy, the main abnormality on light microscopy was acute proximal tubule damage, and the presence of intracytoplasmic inclusions. Electron microscopy showed widespread morphologic abnormalities in proximal tubule mitochondria, with marked variations in size and shape , disruption of cristae, mitochondrial swelling, and intra-mitochondrial deposits [7,14]. It is well known that mitochondrial damage can result in the overproduction of reactive oxygen species (ROS) and reactive nitrogen species (RNS), which upon accumulation can cause oxidative and nitrosative damage to the lipids, proteins and DNA [15,16]. Proximal tubular cells have a requirement for ATP for the active reabsorption of filtered nutrients and ions. Thus, damage to the proximal tubular mitochondria can have two consequences, proximal tubular dysfunction resulting in Fanconi Syndrome and increased production of ROS thereby resulting in increased oxidant stress. Oxidative stress is inseparably linked to mitochondrial dysfunction, as mitochondria are both generators of and targets for reactive species [17]. Because of the deleterious effects of ROS, the cell is equipped with several antioxidants and antioxidant enzyme systems to detoxify ROS produced [18,19]. Oxidative stress is reported to occur in tissues only after the antioxidant (AO) defense mechanisms are depleted, leaving ROS to attack the cellular macromolecules such as lipids, proteins, and DNA. Lipid peroxidation and protein carbonyl content are two important parameters to assess the oxidative damage to lipids (and other constituents) and proteins, respectively. Protein carbonyl groups represent an irreversible protein modification, often leading to the inactivation of the proteins [20]. Protein carbonyl content (Pco) is reported to be a sensitive and early marker of oxidative stress to tissues as compared with TBARS [21]. Superoxide anion is the principal ROS produced by the mitochondria mainly from electron transport chain (ETC.). Superoxide Dismutase (SOD) is first line of defense against superoxide which is the principal ROS produced by the mitochondria and it catalyzes the dismutation of superoxide radicals to hydrogen peroxide and molecular oxygen [22]. Glutathione peroxidase, peroxiredoxins, and catalase decompose hydrogen peroxide generated by SOD to water. T.