Journal of Diseases and Medicinal Plants

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Transdermal Drug Delivery of Asiatic Acid Influences Renal Function and Electrolyte Handling in Plasmodium berghei - Infected Sprague-Dawley Male Rats

Received: 24 October 2017    Accepted: 20 November 2017    Published: 3 April 2018
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Abstract

Background: Malaria is one of the most important infectious inflammatory diseases worldwide which affects vital organs including gastrointestinal and kidneys. Higher prevalence of malaria related renal failure, current malaria drugs nephrotoxicity and drug resistance to malaria calls for continued research in anti-parasitic as well as anti-disease inflammatory pharmaceuticals. Asiatic acid, a plant phytochemical extract, has antioxidant, pro-oxidant and diuretic properties. Here we report influence of Asiatic acid-pectin hydrogel matrix patch application in P. berghei-infected Sprague Dawley rats on renal function and electrolyte handling. Materials and Methods: Asiatic acid (5mg/kg)-pectin patch was applied on the dorsal neck region of the rat on day 7 post infection and monitored for parasitaemia, and physicochemical changes. Urine and blood were collected for measuring various biochemical parameters to estimate renal function and electrolyte handling. Results: Asiatic acid-pectin patch application had significant influence on food and water intake as well as weight changes, urine electrolytes, glomerular filtration rate, and antioxidant markers together with hormonal changes of aldosterone and vasopressin. Conclusion: Application of the once-off Asiatic acid (5mg/kg)-pectin patch influence renal function and renal electrolyte handling while ameliorating, biochemical and hormonal derangements induced by malaria. Novelty of the Work Here we show for the first time a) the efficacy of Asiatic acid (AA) in suppressing murine malaria by way of administering the phytochemical using the amidated pectin hydrogel matrix patch transdermal drug delivery system, b) diminution of asiatic acid dose applied from 10mg/kg oral to 5mg/kg by transdermal, c) reduction of time once-off patch application from five days to three days, d) attenuation of oxidative and hormonal derangements in malaria and e) the amelioration of renal function together with improvement in renal electrolyte handling. The results may be of benefit in patient care replacing the multiple dosing approaches used in malaria management.

DOI 10.11648/j.jdmp.20180401.13
Published in Journal of Diseases and Medicinal Plants (Volume 4, Issue 1, February 2018)
Page(s) 18-29
Creative Commons

This is an Open Access article, distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution and reproduction in any medium or format, provided the original work is properly cited.

Copyright

Copyright © The Author(s), 2024. Published by Science Publishing Group

Keywords

Asiatic Acid, Malaria, Transdermal Drug Delivery, Plasmodium berghei, Sprague Dawley Rats, Renal Failure

References
[1] Ahmed M H and Osman M M. (2007) Why does chloroquine impair renal function? Chloroquine may modulate the ranal tubular response to vasopressin either directly by inhibiting cyclic AMP generation, or indirectly via nitric oxide. Med Hypothesis. 68 (1): 140-143.10.1016/j.mehy.2006.06.012.
[2] Amin N, Alvi N S, Barth J H, Field H P, Finlay E, Tyerman K, et al. (2013) Pseudohypoaldosteronism type 1: clinical features and management in infancy. Endocrine Diabet Metab case report. 13: 0010.10.1530/EDM-13-0010.
[3] Barsoum R S. (2000) Malarial aute renal failure. J Am Soc Nephrol 11: 2147–2154.
[4] Changa K-H and Stevenson M M. (2004) Malarial anaemia: mechanisms and implications of insufficient erythropoiesis during blood-stage malaria. Internat J Parasitol 34: 1501–1516.
[5] Clark I A and Cowden W B. (2003) The pathophysiology of falciparum malaria. Pharmacol Therapeut 99: 221-260.
[6] Feasey N A, Dougan G, Kingsley R A, Heyderman R S, and Gordon M A. (2012) Invasive non-typhoidal salmonella disease: an emerging and neglected tropical disease in Africa. Lancet 363. 79: 2489-2499.10.1016/S0140-6736 (11) 61752-2.
[7] Forbes J M, Coughlan M T and Cooper M E. (2008) Oxidative Stress as a Major Culprit in Kidney Disease in Diabetes. Diabetes 57 (6): 1446-1454.http://dx.doi.org/10.2337/db08-0057.
[8] Ghosh K and Ghosh K. (2007) Pathogenesis of anemia in malaria: a concise review. Parasitol Res 101: 1463-1469.10.1007/s00436-007-0742-1.
[9] Gumede B, Folbb P and Ryffela B. (2003) Oral artesunate prevents Plasmodium berghei Anka infection in mice. Parasitol Internation. 52: 53-59.
[10] Guzman N J, Fang M Z, Tang S S, Ingelfinger J R, and Garg L C. (1995) Autocrine inhibition of Na +/K + -ATPase by nitric oxide in mouse proximal tubule epithelial cells. J Clin Invest 95: 2083–2088.
[11] Hanson J, Hossain A, Charunwatthana P, Hassan M U, Davis T M E, Lam S W K, et al. (2009) Hyponatremia in Severe Malaria: Evidence for an Appropriate Anti-diuretic Hormone Response to Hypovolemia. Am J Trop Med Hyg 80 (1): 141-145.
[12] Huang S-S, Chiu C-S, Chen H-J, Hou W-C, Sheu M-J, Lin Y-C, et al. (2011) Antinociceptive Activities and the Mechanisms of Anti-Inflammation of Asiatic Acid in Mice. Evid-Based Complemen Altern Med. 2011: 10 pages.10.1155/2011/895857.
[13] Karney W W and Tong M J. (1972) Malabsorption in Plasmodium falciparum malaria. Am J Trop Med Hyg 21: 1-5.
[14] Kasapoglu M and Özben T. (2001) Alterations of antioxidant enzymes and oxidative stress markers in aging. Experiment Gerontol 36: 209-220.
[15] Kateera F, Ingabire C H, Hakizimana E, Kalinda P, Mens P F, Grobusch M P, et al. (2015) Malaria, anaemia and under‑nutrition: three frequently co‑existing conditions among preschool children in rural Rwanda. Malaria J 14: 440.10.1186/s12936-015-0973-z.
[16] Khan F Y. (2009) An imported case of P. falciparum malaria presenting as black water fever with acute renal failure.. Travel Med Infect Dis.; 7: 378-380.
[17] Khan R, Quaiser S and Haque S F. (2013) Malarial acute kidney injury: Prognostic markers. Ann Trop Med Public Health 6: 280-284.
[18] Locatelli F, Canaud B, Eckardt K-U, Stenvinkel P, Wanner C, and Zoccali C. (2003) Oxidative stress in end-stage renal disease: an emerging threat to patient outcome. Nephrol Dial Transplant. 18: 1272-1280.10.1093/ndt/gfg074.
[19] Maitland K and Marsh K. (2004) Pathophysiology of severe malaria in children. Acta Tropica 90 131-140.
[20] Mavondo G A, Mkhwananzi B N and Mabandla M V. (2016) Pre-infection administration of asiatic acid retards parasitaemia induction in Plasmodium berghei murine malaria infected Sprague Dawley rats. Malar J. 15: 226.10.1186/s12936-016-1278-6.
[21] Mavondo G A, Mkhwanazi B N and Mabandla M V. (2016) Pre-infection administration of Asiatic acid retards parasitaemia induction in P. berghei murine malaria infected Sprague-Dawley rats Malar J. 15: 226.
[22] Mavondo G A, Mkhwanazi B N, Mabandla M V, and Musabayane C T. (2016) Asiatic acid influences parasitaemia reduction and ameliorate malaria anaemia in P. berghei infected Sprague Dawley male rats. BMC CAM. Inprint.
[23] Mavondo G A and Musabauane C T. (2016) Asiatic acid-pectin hydrogel matrix patch transdermal delivery system influences parasitaemia suppression and inflammation reduction in P. berghei murine malaria infected Sprague-Dawley rats. APJTM 9: 1172-1180.http://dx.doi.org/10.1016/j.apjtm.2016.10.008.
[24] Miller L H, Ackerman H C, Su X-z, and Wellems T E. (2013) Malaria biology and disease pathogenesis: insights for new treatments. Nature Med. 19 (2): 156-167.
[25] Moxon C A, Wassmer S C, Milner D A J, Chisala N V, Taylor T E, and Seydel K B. (2013) Loss of endothelial protein C receptors links coagulation and inflammation to parasite sequestration in cerebral malaria in African children. Blood. 122 (5): 842-851.
[26] Murambiwa P, Tufts M, Mukaratirwa S, van Heerden F R, and Musabayane C T. (2013) Evaluation of efficacy of transdermal delivery of chloroquine on Plasmodium berghei-infected male Sprague-Dawley rats and effects on blood glucose and renal electrolyte handling. Endocrine Abstracts 13: P203.10.1530/endoabs.31. P203.
[27] Musabayane C T, Munjeri O and Matavire T P. (2003) Transdermal delivery of chloroquine by amidated pectin hydrogel matrix patch in the rats. Renal failure. 25: 525-534.
[28] Musabayane C T, Munjeri O P and Matavire B. (2003) Transdermal Delivery of Chloroquine by Amidated Pectin Hydrogel Matrix Patch in the Rat. Renal failure 25: 525-553.
[29] Musabayane C T, Ndhlovu C E, Mamutse G, Bwititi P, and Balment R J. (1993) Acute chloroquine administration increases renal sodium excretion J Tropic Med Hyg 96: 305-310.
[30] Musabayane C T, Wargent E T and Balment R J. (2000) Chloroquine inhibits arginine vasopressin production in isolated rat inner medullary segments induced cAMP collecting duct. Renal Failure. 22: 27-37.
[31] Musabayane C T, Windle R J, Forsling M L, and Balment R J. (1996) Arginine vasopressin mediates the chloroquine induced increase in renal sodium excretion,. Tropic Med Internat Health 1: 542-550.
[32] Naicker S, Aboud O and Gharbi M B. (2008) Epidemiology of acute kidney injury in Africa. Semin Nephrol. 28 348-353.10.1016/j.semnephrol.2008.04.003.
[33] Naqvi R, Ahmad E, Akhtar F, Naqvi A, and Rizvi A. (2003) Outcome in severe acute renal failure associate with malaria. Nephrol Dial Transplant. 18: 1820-1823.
[34] Olsson R A and Johnston E H. (1969) Histopathologic changes and small-bowel absorption in falciparum malaria. Am J Trop Med Hyg 18: 355-359.
[35] Pakdeechote P, Bunbupha S, Kukongviriyapan U, Prachaney P, Chrisanapant W, and Kukongviriyapan V. (2014) Asiatic Acid Alleviates Hemodynamic and Metabolic Alterations via Restoring eNOS/iNOS Expression, Oxidative Stress, and Inflammation in Diet-Induced Metabolic Syndrome Rats. Nutrients 6 (1): 355-370.10.3390/nu6010355.
[36] Patel H, Dhangar K, Sonawane Y, Surana S, Karpoormath R, Thapliyal N, et al. (2015) In search of selective 11 beta-HSD type 1 inhibitors without nephrotoxicity: An approach to resolve the metabolic syndrome by virtual based screening. Arabian J Chem 10.1016/j.arabjc.2015.08.003.
[37] Pino P, Vouldoukis I and Kolb J P. (2003) Plasmodium falciparum-infected erythrocyte adhesion induces caspase activation and apoptosis in human endothelial cells. J Infect Dis 187: 1283-1290.
[38] Plewes K, Haider H S, Kingston H W F, Yeo T W, Ghose A, Hossain A A, et al. (2015) Severe falciparum malaria treated with artesunate complicated by delayed onset haemolysis and acute kidney injury. Malar J 14: 246.10.1186/s12936-015-0760-x.
[39] Prasad R N and Virk K J. (1993) Malaria as a cause of diarrhoea-a review. P N G Med J 36: 337-341.
[40] Reisinger E C, Fritzsche C, Krause R, and Krejs G J. (2005) Diarrhea caused by primarily non-gastrointestinal infections. Nat Clin Pract Gastroenterol Hepatol. 2: 216-222.
[41] Roczniak A and Burns K D. (1996) Nitric oxide stimulates guanylate cyclase and regulates sodium transport in rabbit proximal tubule. Am J Physiol 270: F106–F115.
[42] Rolling T, Agbenyega T, Issifou S, Adegnika A A, Sylverken J, and Spahlinger D e a. (2014) Delayed hemolysis after treatment with parenteral artesunate in African children with severe malaria-a double-center prospective study. J Infect Dis 209: 1921-1928.
[43] Salman I M, Sattar M A, Abdullah N A, Ameer O Z, Basri B, Hussain N M, et al. (2010) Renal functional & haemodynamic changes following acute unilateral renal denervation in Sprague Dawley rats. Indian J Med Res 131: 76-82.
[44] Singh S, Gautam A, Sharma A, and Batra A. (2010) Centella asiatica (L): a plant with immense medicinal potential but threatened. Intern J Pharceut Scie Rev Res. 4 (2): 9-12.
[45] Taniguchi T, Miyauchi E, Nakamura S, Hirai M, Suzue K, Imai T, et al. (2015) Plasmodium berghei ANKA causes intestinal malaria associated with dysbiosis. Scientific Reports 5 (Article number: 15699).
[46] Tholon I, Neliat G, Chesne C, Saboureau D, Perrier E, and Branka J E. (2002) An in vitro, ex vivo, and in vivo demonstration of the lipolytic effect of slimming liposomes: An unexpected α (2)-adrenergic antagonism. J Cosmet Sci. 6: 209-218.
[47] van Wolfswinkel M E, Hesselink D A, Zietse R, Hoorn E J, and vanGenderen P J. (2010) Hyponatraemia in imported malaria is common and associated with disease severity. Malar J. 9: 140.10.1186/1475-2875-9-140.
[48] WHO. (1990) Severe and complicated malaria. World Health Organization, Division of Control of Tropical Diseases. Trans R Soc Trop Med Hyg 84 (Suppl 2): 1-65.
[49] Wilairatana P, Meddings J B, Ho M, Vannaphan S, and Looareesuwan S. (1997) Increased gastrointestinal permeability in patients with Plasmodium falciparum malaria. Clin Infect Dis 24: 430-435.
[50] XU M F, XIONG Y Y, LIU J K, QIAN J J, Zhu L, and GAO J. (2012) Asiatic acid, a pentacyclic triterpene in Centella asiatica, attenuates glutamate-induced cognitive deficits in mice and apoptosis in SH-SY5Y cells. Acta Pharmacol Sinic. 33: 578-587.
[51] Yan S-L, Yang H-T, Lee Y-L, Lin C-C, Chang M-H, and Yin M-C. (2014) Asiatic Acid Ameliorates Hepatic Lipid Accumulation and Insulin Resistance in Mice Consuming a High-Fat Diet. J Agric Food Chem 62 4625−4631.10.1021/jf501165z.
[52] Zhang J, Lisha A I, Tingting L V, Jiang X, and Liu F. (2013) Asiatic acid, a triterpene, inhibits cell proliferation through regulating the expression of focal adhesion kinase in multiple myeloma cells. Oncol letters. 6: 1762-1766.10.3892/ol.2013.1597.
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    Mavondo Greanious Alfred, Musabayane Cephas Tagumirwa. (2018). Transdermal Drug Delivery of Asiatic Acid Influences Renal Function and Electrolyte Handling in Plasmodium berghei - Infected Sprague-Dawley Male Rats. Journal of Diseases and Medicinal Plants, 4(1), 18-29. https://doi.org/10.11648/j.jdmp.20180401.13

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    Mavondo Greanious Alfred; Musabayane Cephas Tagumirwa. Transdermal Drug Delivery of Asiatic Acid Influences Renal Function and Electrolyte Handling in Plasmodium berghei - Infected Sprague-Dawley Male Rats. J. Dis. Med. Plants 2018, 4(1), 18-29. doi: 10.11648/j.jdmp.20180401.13

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    AMA Style

    Mavondo Greanious Alfred, Musabayane Cephas Tagumirwa. Transdermal Drug Delivery of Asiatic Acid Influences Renal Function and Electrolyte Handling in Plasmodium berghei - Infected Sprague-Dawley Male Rats. J Dis Med Plants. 2018;4(1):18-29. doi: 10.11648/j.jdmp.20180401.13

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  • @article{10.11648/j.jdmp.20180401.13,
      author = {Mavondo Greanious Alfred and Musabayane Cephas Tagumirwa},
      title = {Transdermal Drug Delivery of Asiatic Acid Influences Renal Function and Electrolyte Handling in Plasmodium berghei - Infected Sprague-Dawley Male Rats},
      journal = {Journal of Diseases and Medicinal Plants},
      volume = {4},
      number = {1},
      pages = {18-29},
      doi = {10.11648/j.jdmp.20180401.13},
      url = {https://doi.org/10.11648/j.jdmp.20180401.13},
      eprint = {https://article.sciencepublishinggroup.com/pdf/10.11648.j.jdmp.20180401.13},
      abstract = {Background: Malaria is one of the most important infectious inflammatory diseases worldwide which affects vital organs including gastrointestinal and kidneys. Higher prevalence of malaria related renal failure, current malaria drugs nephrotoxicity and drug resistance to malaria calls for continued research in anti-parasitic as well as anti-disease inflammatory pharmaceuticals. Asiatic acid, a plant phytochemical extract, has antioxidant, pro-oxidant and diuretic properties. Here we report influence of Asiatic acid-pectin hydrogel matrix patch application in P. berghei-infected Sprague Dawley rats on renal function and electrolyte handling. Materials and Methods: Asiatic acid (5mg/kg)-pectin patch was applied on the dorsal neck region of the rat on day 7 post infection and monitored for parasitaemia, and physicochemical changes. Urine and blood were collected for measuring various biochemical parameters to estimate renal function and electrolyte handling. Results: Asiatic acid-pectin patch application had significant influence on food and water intake as well as weight changes, urine electrolytes, glomerular filtration rate, and antioxidant markers together with hormonal changes of aldosterone and vasopressin. Conclusion: Application of the once-off Asiatic acid (5mg/kg)-pectin patch influence renal function and renal electrolyte handling while ameliorating, biochemical and hormonal derangements induced by malaria. Novelty of the Work Here we show for the first time a) the efficacy of Asiatic acid (AA) in suppressing murine malaria by way of administering the phytochemical using the amidated pectin hydrogel matrix patch transdermal drug delivery system, b) diminution of asiatic acid dose applied from 10mg/kg oral to 5mg/kg by transdermal, c) reduction of time once-off patch application from five days to three days, d) attenuation of oxidative and hormonal derangements in malaria and e) the amelioration of renal function together with improvement in renal electrolyte handling. The results may be of benefit in patient care replacing the multiple dosing approaches used in malaria management.},
     year = {2018}
    }
    

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  • TY  - JOUR
    T1  - Transdermal Drug Delivery of Asiatic Acid Influences Renal Function and Electrolyte Handling in Plasmodium berghei - Infected Sprague-Dawley Male Rats
    AU  - Mavondo Greanious Alfred
    AU  - Musabayane Cephas Tagumirwa
    Y1  - 2018/04/03
    PY  - 2018
    N1  - https://doi.org/10.11648/j.jdmp.20180401.13
    DO  - 10.11648/j.jdmp.20180401.13
    T2  - Journal of Diseases and Medicinal Plants
    JF  - Journal of Diseases and Medicinal Plants
    JO  - Journal of Diseases and Medicinal Plants
    SP  - 18
    EP  - 29
    PB  - Science Publishing Group
    SN  - 2469-8210
    UR  - https://doi.org/10.11648/j.jdmp.20180401.13
    AB  - Background: Malaria is one of the most important infectious inflammatory diseases worldwide which affects vital organs including gastrointestinal and kidneys. Higher prevalence of malaria related renal failure, current malaria drugs nephrotoxicity and drug resistance to malaria calls for continued research in anti-parasitic as well as anti-disease inflammatory pharmaceuticals. Asiatic acid, a plant phytochemical extract, has antioxidant, pro-oxidant and diuretic properties. Here we report influence of Asiatic acid-pectin hydrogel matrix patch application in P. berghei-infected Sprague Dawley rats on renal function and electrolyte handling. Materials and Methods: Asiatic acid (5mg/kg)-pectin patch was applied on the dorsal neck region of the rat on day 7 post infection and monitored for parasitaemia, and physicochemical changes. Urine and blood were collected for measuring various biochemical parameters to estimate renal function and electrolyte handling. Results: Asiatic acid-pectin patch application had significant influence on food and water intake as well as weight changes, urine electrolytes, glomerular filtration rate, and antioxidant markers together with hormonal changes of aldosterone and vasopressin. Conclusion: Application of the once-off Asiatic acid (5mg/kg)-pectin patch influence renal function and renal electrolyte handling while ameliorating, biochemical and hormonal derangements induced by malaria. Novelty of the Work Here we show for the first time a) the efficacy of Asiatic acid (AA) in suppressing murine malaria by way of administering the phytochemical using the amidated pectin hydrogel matrix patch transdermal drug delivery system, b) diminution of asiatic acid dose applied from 10mg/kg oral to 5mg/kg by transdermal, c) reduction of time once-off patch application from five days to three days, d) attenuation of oxidative and hormonal derangements in malaria and e) the amelioration of renal function together with improvement in renal electrolyte handling. The results may be of benefit in patient care replacing the multiple dosing approaches used in malaria management.
    VL  - 4
    IS  - 1
    ER  - 

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Author Information
  • College of Health Sciences, University of Kwa Zulu Natal, Durban, South Africa; Pathology Department, National University of Science and Technology (NUST), Bulawayo, Zimbabwe

  • Pathology Department, National University of Science and Technology (NUST), Bulawayo, Zimbabwe

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