Abd Ellah, Mahmoud R.

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Mahmoud R. Abd Ellah

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Involvement of Free Radicals in Diseases of the Urinary System

Journal of Advanced Veterinary Research (University Assiut, Egypt)

Free radicals are identified as molecules having oneor more unpaired electrons in their outer orbits, thename radicals means unstable. Free radicals gainthe stability by attracting electrons from neighbor-ing molecules as proteins, enzymes, lipids or aminoacids (Abd Ellah, 2013a). They are highly reactivesubstances produced continuously during meta-bolic processes and participating mainly in physi-ological events such as immune response,metabolism of unsaturated fatty acids, and inflam-matory reactions. The most important free radicalsinclude superoxide anion (O2.−), hydroxyl radical(.OH), and hypochlorous acid (Stohs, 1995; AbdEllah, 2010). Generally, sources of free radicals areoxidative phosphorylation through the mitochon-drial electron transport chain, cytochrome P450 en-zymes, oxidase enzymes like NADPH oxidases.Furthermore, capillaries of the glomerular and tu-bular cells, circulating leucocytes and platelets rep-resent important sources for production of freeradicals (Wardle, 2005). It has long been recog-nized that reactive oxygen species (ROS) are harm-ful for cells, mainly because they leads to structuraland functional impairments of lipids, proteins, andnucleic acids (Freeman and Crapo, 1982; Mantleand Preedy, 1999).Role of antioxidants in renal diseasesThe cells contain a variety of antioxidants mecha-nisms that play a central role in the protectionagainst ROS (Pár and Jávor, 1984; Halliwell,1991). The antioxidant system is classified into twomajor parts: the first one is the antioxidant en-zymes, which include superoxide dismutase(SOD), catalase, glutathione peroxidase (GSH-Px),and ancillary enzymes (glutathione reductase (GR),glutathione S-transferase, and glucose 6-phosphatedehydrogenase. The second class of antioxidants isvitamins including alpha-tocopherol, ascorbate,and beta-carotene (Halliwell, 1994; Abd Ellah,2010). Both the enzymatic and non-enzymatic an-tioxidants become overwhelmed during oxidativestress, due to excessive generation of ROS. Chain breaking antioxidants include vitamin E,C and beta-carotene represent the second line ofdefense that protects different tissues against ox-idative stress. Vitamin E is located both intracellu-larly and extracellularly; one of its functions is toimprove the oxidative status and to remove lipidperoxy radicals formed during the process of in-creased oxidative stress (Cristol et al., 1997). Onthe other hand, vitamin C has sparing effect on vi-tamin E, as it helps recycling of α-tocopherol fromits oxidized form to native form. The role of ascor-bic acid and vitamin E in relieve of renal diseaseshas been established by many studies; decreased ofascorbic acid and vitamin E levels in sera of uremicpatients were reported by Giardini et al. (1984) andFrei et al. (1989). Also, decreased oxidative stressand relieve of renal cell injury were observed aftersupplementation of vitamin C (Frei et al., 1989).Supplementation of vitamin E suppresses oxidativestress and retards kidney failure (Gorgum et al.,1999). Furthermore, dietary treatment with vitaminE diminished renal functional and structuralchanges in experimental glomerulopathy in rats(Trachtman et al., 1996).  Oxidative stress and renal diseasesCellular release of free radicals is controlled by thedefense mechanism in the form of antioxidants.Over production of free radicals and/or decreasethe antioxidants defence mechanisms are the mainpredisposing cause for the occurrence of oxidativestress (Abd Ellah, 2013b). Furthermore, neu-trophils get attracted to the site of inflammation un-dergo a ‘respiratory burst’ resulting in excessive*Corresponding author: M.R. Abd Ellah.E-mail address: mrushdi@aun.edu.egJournal of Advanced Veterinary ResearchVolume 3 (2013) 52-56Involvement of Free Radicals in Diseases of the Urinary SystemMahmoud R. Abd Ellah*Department of Animal Medicine, Faculty of Veterinary Medicine, Assiut University 71526, EgyptEditorialISSN: 2090-6277/2090-6269, www.advetresearch.comproduction of oxygen free radicals (Paller and Hed-lund, 1988). In many experimental studies, the par-ticipation of reactive oxygen species (ROS) inglomerular damage was confirmed by measuringthe products of oxidant injury and antioxidants lev-els in renal tissue and urine (Wojcicka and Bel-towski 2001). Many toxic chemicals inducenephrotoxicity through the generation of ROS assuggested by Somani et al. (2000). Also, tissuedeposition of immune complexes can induce anacute inflammatory response resulting in tissue in-jury. Many research studies had been reported thatoxidative stress mediates a wide range of renal in-juries, which ranging from acute renal failure(Paller et al., 1998; Baliga et al., 1999; Shah,2001), rhabdomyolysis (Vanholder et al., 2000),obstructive nephropathy (Klahr, 2001), hyperlipi-demia (Wanner et al., 1997; Sakatsume et al.,2001) and glomerular damage (Kitamura andIshikawa, 1999) to chronic renal failure (Handel-man et al., 2001). Studies in models of acute renalfailure (ARF) have generated evidence that ROSproduction occurs during ischemia/reperfusion(Greene and Paller 1991).Reactive oxygen species are involved in thepathogenesis of toxic, ischemic, immunologicallymediated renal injury (Baude and Ardaillou 1993)and chronic renal failure (CRF). The increased pro-duction of ROS in CRF may be related to meta-bolic consequences of the uremia such as decreasedproduction of NADPH (Yawata and Jacob, 1975)and GSH-Px activity (Schiavon et al., 1994) andlowered vitamin E level (Yalcin et al., 1989). Thepotential consequences of increased generation ofROS in CRF are accelerated atherosclerosis (Greenet al., 1983) and increased RBCs rigidity, whichmay shorten erythrocyte life span and contribute torenal anemia (Kikuchi et al., 1982 and (Delmas-Beauvieux et al., 1995). Some studies consideredoxidative stress in CRF as an important source ofpatient morbidity and mortality, through their in-volvement in the pathogenesis of malnutrition(Galle, 2001, Maggi et al., 1994; Galle et al.,2003), anaemia (Taccone-Gallucci et al., 1999),and increased risk of cancerogenesis (Vamvakas etal., 1998).Studying the status of the oxidative stress in an-imals is lacking. In one study, vitamin antioxidantssuch as vitamin E, C and β-carotene levels weremeasured in blood of camels suffered from cystitis(Abd Ellah et al., 2012), the authors reported de-crease serum vitamin C level in camels withchronic cystitis compared with those suffered fromacute cystitis, and decreases in serum α-tocopheroland  β-carotene  levels  in  both  acute  and chroniccystitis affected camels, which indicated the exces-sive production of free radicals that assimilateavailable vitamin C (Tappe, 1968).Dogs with renal azotaemia were reported tohave a higher intra-erythrocytic CAT activity. How-ever, glutathione content and plasma malondialde-hyde (MDA) level were unaltered (Buranakarl etal., 2009).The antioxidant vitamin E amelioratesthe effects of glomerular disease. Dietary treatmentwith the antioxidant vitamin E attenuated renalfunctional and structural changes in experimentalglomerulopathy (Trachtman et al., 1996). It wasdemonstrated that and vitamins A, C, and E have aprotective role against LPO of erythrocytes in pa-tients with CRF. Auto-transplantation method in canine is a goodmodel to evaluate the problems of ischemia– reper-fusion (I/R) injury. The reperfusion injury causedby oxidative stress is relieved by antioxidant sup-plementation. In a renal transplantation model,ascorbic acid alone was reported to play a role inattenuating I/R injury and assisted in the recoveryof the renal function (Lee et al., 2006). Lipid peroxidation in renal diseasesThere are some predisposing factors for the forma-tion of lipid peroxidation in tissues. One of thesefactors is the increased destruction of cells espe-cially in renal ischemia, which associated withoverproduction of free radicals. Another importantfactor is the decrease of antioxidants, which be-come evident with the progress of the diseases. Thepresence of the two factors or one of them may re-sult in lipid peroxidation. In addition, cell mem-brane contains high amount of polyunsaturatedfatty acids, which combine with free radicals toform lipid peroxide derivatives. The production offree radicals may cause the progress of the renal in-jury to acute renal failure, especially after is-chaemic renal injury as reported by Mark et al.(1984); Ratych and Bulkley (1986); Greene andPaller (1991) and Rao Srinivasa et al. (1996). Inpatients with chronic renal failure, increased pro-duction of free radicals had been reflected by in-creased peroxidation of erythrocyte membranes(Morosetti et al., 1987; Ginevri et al., 1989; To-53M.R. Abd Ellah / Journal of Advanced Veterinary Research 3 (2013) 52-56borek et al., 1992).Lipid peroxidation had been reported in patientswith acute renal failure, which occurred during my-ohemoglobinuria (Abheri et al., 2010) that was ex-plained by the increased iron in the renal tissues,which react with free radicals and predispose to theformation of toxic radicals.ConclusionThe present review threw the light on previous re-searches that aimed to study the response of the ox-idant and antioxidants balance to different diseasesof the urinary system. Studying the oxidative stressin diseases of the urinary system in animals arelacking compared with similar researches inhuman. Further studies are required to elucidate theoxidative status in urinary system diseases in rela-tion to the productive and reproductive capacity ofdifferent animal species.ReferencesAbd Ellah, M.R., 2010. Involvement of free radi-cals in animal diseases. 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Involvement of Free Radicals in Diseases of the Urinary System

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Journal of Advanced Veterinary Research (University Assiut, Egypt)