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      • Record: found
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      Nephrotoxicity and highly active antiretroviral therapy: Mitigating action of Momordica charantia

      research-article
      Author(s): a , * , a , a , b , a , a , c , a , d
      Publication date (Electronic):
      Journal: Toxicology Reports
      Publisher: Elsevier
      Keywords: DTNB, 5, 5'-dithiobis-(2-nitrobenzoic acid), 6-HD, 6-hydroxydopamine, AIDS, acquired immune deficiency syndrome, ALB, albumin, ANOVA, analysis of variance, AREC, animal research ethics committee, BRU, Biomedical Resource Unit, BGL, blood glucose levels, BUN, blood urea nitrogen, BW, body weight, CAT, catalase, DNA, deoxyribonucleic acid, DETAPAC, diethylenetriamine – penta acetic acid, GSH, reduced glutathione, H and E, haematoxylin and eosin, HAART, highly active antiretroviral therapy, HIV, human immunodeficiency virus, KW, kidney weight, KWBR, kidney weight body ratio, LPO, lipid peroxidation, MDA, malondialdehyde, MT, Masson’s Trichome, M. charantia, Momordica charantia, NRTIs, nucleoside reverse transcriptase inhibitors, PLWHA, people living with HIV and AIDS, PAS, Periodic Acid Schiff, PBS, phosphate buffer solution, ROS, reactive oxygen species, rpm, revolutions per minute, SCr, serum creatinine, SDS, sodium dodecyl sulfate, SOD, superoxide dismutase, SD, standard deviation, TBARS, thiobarbituric acid reactive substances, TCA, trichloroacetic acid, UKZN, University of KwaZulu Natal, HAART, Nephrotoxicity, Kidney, Momordica charantia, Histopathology, Sprague-Dawley rats

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          Graphical abstract

          Highlights

          • •

            Highly active antiretroviral therapy (HAART) associated nephrotoxicity is characterized by tubular necrosis with glomerular hypertrophy.

          • •

            Derangements of the cytoarchitectural patterns of the kidney were seen as a result of treatment with HAART regimen (triplavar).

          • •

            Co-administration of M. charantia and HAART mitigates the intensive histopathological changes of the rat kidney.

          • •

            Nephrotoxicity is associated with increased oxidative stress which stems from increased reactive oxygen species (ROS) generation in tissues.

          • •

            M. charantia possesses phytochemical properties which are powerful counter measures against oxidative stress tissue damage.

          Abstract

          Momordica charantia ( M. charantia) is known for its antioxidant and antidiabetic properties. The aim of this study is to investigate the renoprotective effects of M. charantia in rats following treatment with highly active antiretroviral therapy (HAART) regimen triplavar. Adult male Sprague-Dawley rats weighing 178.1–220.5 g (n = 36) were divided into six groups (A–F) with each group comprising of six (n = 6) rats. The drugs and extract were administered via oral gavage. The therapeutic dose of triplavar was adjusted using the human therapeutic dose equivalent for the rat model. Animals were euthanized on the tenth week with kidneys removed for examination and blood obtained via cardiac puncture. Levels of oxidative stress enzymes (superoxide dismutase-SOD, catalase-CAT, and reduced glutathione-GSH) were significantly lowered in all groups not receiving M. charantia. The levels of thiobarbituric acid reactive substances (TBARS) were increased resulting in free radical formation via auto-oxidation. Renal parameters showed no albuminuria, normal blood urea nitrogen (BUN), serum creatinine (SCr) and electrolytes in groups treated with M. charantia. HAART treated (Group B) showed severe albuminuria, a significantly ( p < 0.05) raised BUN and SCr and gross electrolyte disturbances. Blood glucose levels were significantly raised in groups not receiving the adjuvant M. charantia ( p < 0.05). Histopathology in HAART treated animals showed glomerular capillary abnormalities and cellular infiltrations while M. charantia treated animals showed an essentially normal glomerular appearance with capillary loops and normal cytoarchitecture. In conclusion M. charantia extract administration improved blood glucose levels, restored renal histology, reinstate renal function, reduce body weight loss and restores hyperglycemia.

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          Most cited references20

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          Measurement of superoxide dismutase, catalase and glutathione peroxidase in cultured cells and tissue.

          Christine Weydert, Joseph Cullen (2010)
          Cells contain a large number of antioxidants to prevent or repair the damage caused by reactive oxygen species, as well as to regulate redox-sensitive signaling pathways. General protocols are described to measure the antioxidant enzyme activity of superoxide dismutase (SOD), catalase and glutathione peroxidase. The SODs convert superoxide radical into hydrogen peroxide and molecular oxygen, whereas the catalase and peroxidases convert hydrogen peroxide into water. In this way, two toxic species, superoxide radical and hydrogen peroxide, are converted to the harmless product water. Western blots, activity gels and activity assays are various methods used to determine protein and activity in both cells and tissue depending on the amount of protein required for each assay. Other techniques including immunohistochemistry and immunogold can further evaluate the levels of the various antioxidant enzymes in tissues and cells. In general, these assays require 24-48 h to complete.
          Article 0 comments Cited 336 times – based on 0 reviews     Review now
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            Declining Morbidity and Mortality among Patients with Advanced Human Immunodeficiency Virus Infection

            Frank Palella, Kathleen Delaney, Anne C Moorman … (1998)
            National surveillance data show recent, marked reductions in morbidity and mortality associated with the acquired immunodeficiency syndrome (AIDS). To evaluate these declines, we analyzed data on 1255 patients, each of whom had at least one CD4+ count below 100 cells per cubic millimeter, who were seen at nine clinics specializing in the treatment of human immunodeficiency virus (HIV) infection in eight U.S. cities from January 1994 through June 1997. Mortality among the patients declined from 29.4 per 100 person-years in the first quarter of 1995 to 8.8 per 100 in the second quarter of 1997. There were reductions in mortality regardless of sex, race, age, and risk factors for transmission of HIV. The incidence of any of three major opportunistic infections (Pneumocystis carinii pneumonia, Mycobacterium avium complex disease, and cytomegalovirus retinitis) declined from 21.9 per 100 person-years in 1994 to 3.7 per 100 person-years by mid-1997. In a failure-rate model, increases in the intensity of antiretroviral therapy (classified as none, monotherapy, combination therapy without a protease inhibitor, and combination therapy with a protease inhibitor) were associated with stepwise reductions in morbidity and mortality. Combination antiretroviral therapy was associated with the most benefit; the inclusion of protease inhibitors in such regimens conferred additional benefit. Patients with private insurance were more often prescribed protease inhibitors and had lower mortality rates than those insured by Medicare or Medicaid. The recent declines in morbidity and mortality due to AIDS are attributable to the use of more intensive antiretroviral therapies.
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              Tenofovir effect on the kidneys of HIV-infected patients: a double-edged sword?

              Jérôme Tourret, Gilbert Deray, Corinne Isnard Bagnis (2013)
              Tenofovir disoproxil fumarate (TDF), the first nucleotidic inhibitor of HIV reverse transcription, became available in 2001. It has been extensively used worldwide and is now the most prescribed antiretroviral (ARV) drug. Its high antiviral activity and favorable metabolic profile are responsible for its success. Furthermore, TDF has been associated with other ARVs to form new combined antiretroviral treatments in only one tablet once-a-day, which increases treatment adherence. Fears of potential nephrotoxicity that tenofovir would have in common with two other drugs from the same family (adefovir, used to treat hepatitis B, and cidofovir, used to treat cytomegalovirus infections) were alleviated by the early clinical trials. Yet, in 2001, the first case of TDF-induced acute nephrotoxicity was published. Numerous cases have been published since then, and it is now established that TDF presents a tubular toxicity risk. Some facilitating factors have been identified, such as co-prescription of didanosine or boosted protease inhibitor, preexisting CKD, low body weight, and associated diabetes mellitus. Conversely, whether TDF is nephrotoxic in the long term is a highly debated question. Some studies suggest a decreased GFR when TDF is prescribed for a long period, while others indicate that TDF is safe for the kidneys even after many years of use. Here we review the differences in patient characteristics, study designs, and measured outcomes that can possibly explain these conflicting findings. We conclude with rational recommendation for appropriate TDF prescription.
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                Author and article information

                Contributors
                Ugochukwu Offor
                Journal
                Journal ID (nlm-ta): Toxicol Rep
                Journal ID (iso-abbrev): Toxicol Rep
                Title: Toxicology Reports
                Publisher: Elsevier
                ISSN (Electronic): 2214-7500
                Publication date PMC-release: 20 September 2018
                Publication date Collection: 2018
                Publication date (Electronic): 20 September 2018
                Volume: 5
                Pages: 1153-1160
                Affiliations
                [a ]Department of Clinical Anatomy, School of Laboratory Medicine and Medical Sciences, Nelson R Mandela School of Medicine, University of KwaZulu-Natal, South Africa
                [b ]Department of Anatomy, College of Medicine and Health Sciences, Afe Babalola University, Ado Ekiti, Nigeria
                [c ]Department of Anatomy, Faculty of Basic Medical Sciences, University of Uyo-Nigeria, Nigeria
                [d ]Department of Anatomy, School of Medicine, University of Namibia, Windhoek, Namibia
                Author notes
                [* ]Corresponding author at: Department of Clinical Anatomy, School of Laboratory Medicine and Medical Sciences, Nelson R Mandela School of Medicine, University of KwaZulu-Natal, 719, Umbilo Road, Congella, Durban, South Africa. ugochukwuoffor@ 123456yahoo.com
                Article
                Publisher ID: S2214-7500(18)30105-7
                DOI: 10.1016/j.toxrep.2018.09.003
                PMC ID: 6319328
                PubMed ID: 30627515
                SO-VID: f2efda9e-0102-45a2-a558-41b628eaaf67
                Copyright © © 2018 The Authors
                License:

                This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).

                History
                Date received : 22 February 2018
                Date revision received : 3 September 2018
                Date accepted : 15 September 2018
                Categories
                Subject: Article

                Keywords: dtnb, 5, 5'-dithiobis-(2-nitrobenzoic acid),6-hd, 6-hydroxydopamine,aids, acquired immune deficiency syndrome,alb, albumin,anova, analysis of variance,arec, animal research ethics committee,bru, biomedical resource unit,bgl, blood glucose levels,bun, blood urea nitrogen,bw, body weight,cat, catalase,dna, deoxyribonucleic acid,detapac, diethylenetriamine – penta acetic acid,gsh, reduced glutathione,h and e, haematoxylin and eosin,haart, highly active antiretroviral therapy,hiv, human immunodeficiency virus,kw, kidney weight,kwbr, kidney weight body ratio,lpo, lipid peroxidation,mda, malondialdehyde,mt, masson’s trichome,m. charantia, momordica charantia,nrtis, nucleoside reverse transcriptase inhibitors,plwha, people living with hiv and aids,pas, periodic acid schiff,pbs, phosphate buffer solution,ros, reactive oxygen species,rpm, revolutions per minute,scr, serum creatinine,sds, sodium dodecyl sulfate,sod, superoxide dismutase,sd, standard deviation,tbars, thiobarbituric acid reactive substances,tca, trichloroacetic acid,ukzn, university of kwazulu natal,haart,nephrotoxicity,kidney,momordica charantia,histopathology,sprague-dawley rats
                Data availability:
                Keywords: dtnb, 5, 5'-dithiobis-(2-nitrobenzoic acid), 6-hd, 6-hydroxydopamine, aids, acquired immune deficiency syndrome, alb, albumin, anova, analysis of variance, arec, animal research ethics committee, bru, biomedical resource unit, bgl, blood glucose levels, bun, blood urea nitrogen, bw, body weight, cat, catalase, dna, deoxyribonucleic acid, detapac, diethylenetriamine – penta acetic acid, gsh, reduced glutathione, h and e, haematoxylin and eosin, haart, highly active antiretroviral therapy, hiv, human immunodeficiency virus, kw, kidney weight, kwbr, kidney weight body ratio, lpo, lipid peroxidation, mda, malondialdehyde, mt, masson’s trichome, m. charantia, momordica charantia, nrtis, nucleoside reverse transcriptase inhibitors, plwha, people living with hiv and aids, pas, periodic acid schiff, pbs, phosphate buffer solution, ros, reactive oxygen species, rpm, revolutions per minute, scr, serum creatinine, sds, sodium dodecyl sulfate, sod, superoxide dismutase, sd, standard deviation, tbars, thiobarbituric acid reactive substances, tca, trichloroacetic acid, ukzn, university of kwazulu natal, haart, nephrotoxicity, kidney, momordica charantia, histopathology, sprague-dawley rats

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