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      Risperidone-Induced Renal Damage and Metabolic Side Effects: The Protective Effect of Resveratrol

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          Abstract

          Objective

          The aim of the study was to investigate the possible protective qualities of resveratrol (RSV) against the side effects of risperidone (RIS) in an experimental model in rat kidneys with histologic and biochemical assessments.

          Materials and Methods

          Experimental procedures were performed on 35 female Sprague Dawley rats. Rats were randomly divided into five groups: control, untreated rats ( n = 7) were in group 1; group 2 was given 2 mg/kg/day RIS ( n = 7); group 3 was treated with 2 mg/kg/day RIS and 20 mg/kg/day RSV ( n = 7); group 4 was treated with 2 mg/kg/day RIS and 40 mg/kg/day RSV ( n = 7); and group 5 was treated with 2 mg/kg/day RIS and 80 mg/kg/day RSV ( n = 7). All treatments were administered for two weeks by gavage. On treatment day 15, kidney tissues were removed for analysis.

          Results

          The results showed that RSV treatment reduced weight gain induced by RIS. In addition, RSV increased the total antioxidant status (TAS) and decreased serum creatinine (Cr), blood urea nitrogen (BUN), oxidative stress index (OSI), and total oxidant status (TOS) levels significantly ( p < 0.05).

          Conclusion

          This study revealed that treatment with RSV might protect kidney tissues against the side effects of RIS. RSV could be an effective course of therapy to enhance therapeutic efficacy.

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          Atypical antipsychotic drugs and the risk of sudden cardiac death.

          Wayne Ray, Cecilia P Chung, Katherine T Murray … (2009)
          Users of typical antipsychotic drugs have an increased risk of serious ventricular arrhythmias and sudden cardiac death. However, less is known regarding the cardiac safety of the atypical antipsychotic drugs, which have largely replaced the older agents in clinical practice. We calculated the adjusted incidence of sudden cardiac death among current users of antipsychotic drugs in a retrospective cohort study of Medicaid enrollees in Tennessee. The primary analysis included 44,218 and 46,089 baseline users of single typical and atypical drugs, respectively, and 186,600 matched nonusers of antipsychotic drugs. To assess residual confounding related to factors associated with the use of antipsychotic drugs, we performed a secondary analysis of users of antipsychotic drugs who had no baseline diagnosis of schizophrenia or related psychoses and with whom nonusers were matched according to propensity score (i.e., the predicted probability that they would be users of antipsychotic drugs). Current users of typical and of atypical antipsychotic drugs had higher rates of sudden cardiac death than did nonusers of antipsychotic drugs, with adjusted incidence-rate ratios of 1.99 (95% confidence interval [CI], 1.68 to 2.34) and 2.26 (95% CI, 1.88 to 2.72), respectively. The incidence-rate ratio for users of atypical antipsychotic drugs as compared with users of typical antipsychotic drugs was 1.14 (95% CI, 0.93 to 1.39). Former users of antipsychotic drugs had no significantly increased risk (incidence-rate ratio, 1.13; 95% CI, 0.98 to 1.30). For both classes of drugs, the risk for current users increased significantly with an increasing dose. Among users of typical antipsychotic drugs, the incidence-rate ratios increased from 1.31 (95% CI, 0.97 to 1.77) for those taking low doses to 2.42 (95% CI, 1.91 to 3.06) for those taking high doses (P<0.001). Among users of atypical agents, the incidence-rate ratios increased from 1.59 (95% CI, 1 .03 to 2.46) for those taking low doses to 2.86 (95% CI, 2.25 to 3.65) for those taking high doses (P=0.01). The findings were similar in the cohort that was matched for propensity score. Current users of typical and of atypical antipsychotic drugs had a similar, dose-related increased risk of sudden cardiac death. 2009 Massachusetts Medical Society
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            Antipsychotic-induced weight gain: a comprehensive research synthesis.

            D Allison, J L Mentore, M Heo … (1999)
            The purpose of this study was to estimate and compare the effects of antipsychotics-both the newer ones and the conventional ones-on body weight. A comprehensive literature search identified 81 English- and non-English-language articles that included data on weight change in antipsychotic-treated patients. For each agent, a meta-analysis and random effects metaregression estimated the weight change after 10 weeks of treatment at a standard dose. A comprehensive narrative review was also conducted on all articles that did not yield quantitative information but did yield important qualitative information. Placebo was associated with a mean weight reduction of 0.74 kg. Among conventional agents, mean weight change ranged from a reduction of 0.39 kg with molindone to an increase of 3.19 kg with thioridazine. Among newer antipsychotic agents, mean increases were as follows: clozapine, 4.45 kg; olanzapine, 4.15 kg; sertindole, 2.92 kg; risperidone, 2.10 kg; and ziprasidone, 0.04 kg. Insufficient data were available to evaluate quetiapine at 10 weeks. Both conventional and newer antipsychotics are associated with weight gain. Among the newer agents, clozapine appears to have the greatest potential to induce weight gain, and ziprasidone the least. The differences among newer agents may affect compliance with medication and health risk.
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              Resveratrol as an anti-inflammatory and anti-aging agent: mechanisms and clinical implications.

              C. Lastra, Isabel Villegas (2005)
              Resveratrol is a phytoalexin polyphenolic compound found in various plants, including grapes, berries, and peanuts. Multiple lines of compelling evidence indicate its beneficial effects on neurological, hepatic, and cardiovascular systems. Also one of the most striking biological activities of resveratrol soundly investigated during the late years has been its cancer-chemopreventive potential. In fact, recently it has been demonstrated that this stilbene blocks the multistep process of carcinogenesis at various stages: tumor initiation, promotion, and progression. One of the possible mechanisms for its biological activities involves downregulation of the inflammatory response through inhibition of synthesis and release of pro-inflammatory mediators, modification of eicosanoid synthesis, inhibition of activated immune cells, or inhibiting such as inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) via its inhibitory effects on nuclear factor (kappa)B (NF-(kappa)B) or the activator protein-1 (AP-1). More recent data provide interesting insights into the effect of this compound on the lifespan of yeast and flies, implicating the potential of resveratrol as an anti-aging agent in treating age-related human diseases. It is worthy to note that the phenolic compound possesses a low bioavailability and rapid clearance from the plasma. As the positive effects of resveratrol on inflammatory response regulation may comprise relevant clinical implications, the purpose of this article is to review its strong anti-inflammatory activity and the plausible mechanisms of these effects. Also, this review is intended to provide the reader an up-date of the bioavailability and pharmacokinetics of resveratrol and its impact on lifespan.
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                Author and article information

                Journal
                Journal ID (nlm-ta): Oxid Med Cell Longev
                Journal ID (iso-abbrev): Oxid Med Cell Longev
                Journal ID (publisher-id): OMCL
                Title: Oxidative Medicine and Cellular Longevity
                Publisher: Hindawi
                ISSN (Print): 1942-0900
                ISSN (Electronic): 1942-0994
                Publication date (Print): 2017
                Publication date (Electronic): 15 June 2017
                Volume: 2017
                Electronic Location Identifier: 8709521
                Affiliations
                1Vocational School of Health Services, Adıyaman University, Adıyaman, Turkey
                2Department of Histology, Faculty of Medicine, Fırat University, Elazığ, Turkey
                3Department of Pharmacology, Faculty of Medicine, Adıyaman University, Adıyaman, Turkey
                Author notes

                Academic Editor: Ersin Fadillioglu

                Author information
                http://orcid.org/0000-0001-8410-2685
                http://orcid.org/0000-0002-7961-4130
                Article
                DOI: 10.1155/2017/8709521
                PMC ID: 5494574
                PubMed ID: 28706577
                SO-VID: 4abaacd6-3aea-4dc5-81ac-22fc46ee78d9
                Copyright © Copyright © 2017 Sedat Bilgiç et al.
                License:

                This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                Date received : 5 March 2017
                Date accepted : 26 April 2017
                Categories
                Subject: Research Article

                ScienceOpen disciplines: Molecular medicine
                Data availability:
                ScienceOpen disciplines: Molecular medicine

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