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      Effect of Isoproterenol on LDL Susceptibility to Oxidation and Serum Total Antioxidant Capacity in Cyclosporine-Treated Rats

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          Abstract

          Background: Cyclosporine therapy is associated with a variety of adverse effects. Recent studies have suggested increased oxidative stress as a cause of these side effects.

          Objective: Since, melatonin is one of the most powerful known antioxidants, and considering that isoproterenol is one of the drugs stimulating endogenous melatonin production, we tried to determine the effect of isoproterenol on LDL susceptibility to oxidation and serum total antioxidant capacity in cyclosporine-treated rats.

          Methods: 32 male Wistar rats were divided into four groups: group A were controls that received placebo; group B received intraperitoneal isoproterenol (20 mg/kg/d) alone; group C received intravenous cyclosporine (15 mg/kg/d) alone; and group D received both drugs simultaneously at the same doses and durations—cyclosporine one week after administration of isoproterenol. Blood samples were drawn four times from rats in each group: before injections, during the treatment, end of the treatment, and one week after the last injections.

          Results: There was a significant (p<0.05) increase in LDL susceptibility to oxidation, and a decrease in serum total antioxidant capacity (p<0.05) in group C rats. But, there were no significant changes in group B and D rats in terms of LDL susceptibility to oxidation and total antioxidant capacity.

          Conclusion: Isoproterenol may be capable of delaying adverse effects of cyclosporine by preventing the increase in LDL susceptibility to oxidation, and decrease in serum total antioxidant capacity.

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          Most cited references45

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          The Yin and Yang of oxidation in the development of the fatty streak. A review based on the 1994 George Lyman Duff Memorial Lecture.

          Jenny van Odijk, J. Berliner, S Hama … (1996)
          Recent data support the hypothesis that the fatty streak develops in response to specific phospholipids contained in LDL that become trapped in the artery wall and become oxidized as a result of exposure to the oxidative waste of the artery wall cells. The antioxidants present within both LDL and the microenvironments in which LDL is trapped function to prevent the formation of these biologically active, oxidized lipids. Enzymes associated with LDL and HDL (eg, platelet activating factor acetylhydrolase) or with HDL alone (eg, paraoxonase) destroy these biologically active lipids. The regulation and expression of these enzymes are determined genetically and are also significantly modified by environmental influences, including the acute-phase response or an atherogenic diet. The balance of these multiple factors leads to an induction or suppression of the inflammatory response in the artery wall and determines the clinical course.
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            Cyclosporine nephrotoxicity.

            Emmanuel A. Burdmann, Takeshi Andoh, Luis Yu … (2003)
            After more than 20 years of cyclosporine use its nephrotoxicity remains a significant clinical problem. Cyclosporine-induced renal injury has been described in solid organs recipients and in patients treated for autoimmune diseases. It is manifested in 2 distinct and well characterized forms, acute nephrotoxicity and chronic nephrotoxicity. This communication reviews the current literature analyzing the available data about the pathogenesis and mechanisms of acute and chronic cyclosporine-induced nephrotoxicity. A working hypothesis for the possible mechanisms of chronic cyclosporine nephrotoxicity will be provided.
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              Modified forms of low density lipoprotein and atherosclerosis.

              Michael Aviram (1993)
              Modified forms of low density lipoprotein (LDL) are associated with increased atherogenicity. Modified LDL, in comparison with native LDL, demonstrates enhanced cellular uptake by macrophages, foam cell formation and also causes the secretion of cytokines and growth factors from arterial wall cells. Non-enzymatic modifications of LDL (proteoglycans, glycosylation, immune complexes) and enzymatic modifications (lipases, oxygenases) were shown to affect the physicochemical (size, charge) as well as the biological (cellular uptake, secretion) properties of the lipoprotein. Of special interest is the oxidative modification of LDL which was demonstrated to occur in vivo. The mechanism of this process involves cellular lipid peroxidation and requires the binding of LDL to its receptor on macrophages. Some of the modifications can render the LDL more susceptible to other types of modifications (lipid modifications, aggregation, oxidation). As atherosclerosis is a multifactorial disease and since lipases and oxygenases exist in cells of the arterial wall, several forms of modified LDL may exist in vivo. These modifications can occur either in parallel or along different stages of atherogenesis. Inhibition of such LDL modifications may arrest the development of the atherosclerotic lesion.
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                Author and article information

                Journal
                Journal ID (nlm-ta): Int J Organ Transplant Med
                Journal ID (iso-abbrev): Int J Organ Transplant Med
                Journal ID (publisher-id): Ijotm
                Title: International Journal of Organ Transplantation Medicine
                Publisher: Avicenna Organ Transplantation Institute (Shiraz, Iran )
                ISSN (Print): 2008-6482
                ISSN (Electronic): 2008-6490
                Publication date (Print): 2010
                Publication date (Electronic): 1 August 2010
                Volume: 1
                Issue: 3
                Pages: 139-145
                Affiliations
                [1 ] I.A.U. Tabriz Branch, Young Researchers Club, Tabriz, Iran,
                [2 ] Drug Applied Research Center, Tabriz University of Medical Sciences, Tabriz 51664, Iran,
                [3 ] Biotechnology Research Center, Tabriz University of Medical Sciences, Tabriz 51664, Iran,
                [4 ] Shahid Beheshti University of Medical Sciences, Tehran, Iran
                Author notes
                [* ]Correspondence: H. Argani, MD, Shahid Beheshti University of Medical Sciences, Tehran, Iran. E-mail: hassanargani@ 123456gmail.com
                Article
                Publisher ID: ijotm-1-139
                PMC ID: 4089234
                SO-VID: 85376088-4c8a-4eea-aaf9-f74865909ed6
                License:

                This is an Open Access article distributed under the terms of the Creative Commons Attribution License, ( http://creativecommons.org/licenses/by/3.0/) which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                Categories
                Subject: Original Article

                Keywords: isoproterenol,cyclosporine,ldl susceptibility to oxidation,total antioxidant,rat
                Data availability:
                Keywords: isoproterenol, cyclosporine, ldl susceptibility to oxidation, total antioxidant, rat

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