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Triterpene derivative improves the renal function of streptozotocin-induced diabetic rats: a follow-up study on maslinic acid.

Authors
  • Mkhwanazi, Blessing Nkazimulo1
  • van Heerden, Fanie Retief2
  • Mavondo, Greanious Alfred3
  • Mabandla, Musa Vuyisile4
  • Musabayane, Cephas Tagumirwa4
  • 1 a School of Agricultural, Earth & Environmental Sciences , University of KwaZulu-Natal , Scottsville , South Africa. , (South Africa)
  • 2 b School of Chemistry and Physics , University of KwaZulu-Natal , Scottsville , South Africa. , (South Africa)
  • 3 c Faculty of Medicine , National University of Science and Technology (NUST) , Bulawayao , Zimbabwe. , (Zimbabwe)
  • 4 d School of Laboratory Medicine and Medical Sciences , University of KwaZulu-Natal , Durban , South Africa. , (South Africa)
Type
Published Article
Journal
Renal Failure
Publisher
Informa UK (Taylor & Francis)
Publication Date
Nov 01, 2019
Volume
41
Issue
1
Pages
547–554
Identifiers
DOI: 10.1080/0886022X.2019.1623818
PMID: 31234683
Source
Medline
Keywords
Language
English
License
Unknown

Abstract

Introduction: Reports indicate that oral administration of plant-derived maslinic acid (MA) exhibits hypoglycemic and renoprotective effects in streptozotocin (STZ)-induced diabetic rats. Challenges with triterpenes such as MA include low bioavailabilty which affects treatment efficacy in experimental animals. The goal of this study was to synthesize the MA derivative phenylhydrazine (PH-MA) in an effort to improve the efficacy of MA. Methods: Separate groups of non-diabetic and STZ-induced diabetic rats (n = 6) were anesthetized and the jugular vein cannulated for the infusion of 0.077 M NaCl at 9 mL/h. The bladder was catheterized for collection the urine samples every 30 min. After 30.5 h equilibration period, consecutive 30 min urine collections were made over the subsequent 4 h of 1 h control, 1.5 h treatment, and 1.5 h recovery periods. PH-MA (22 µg/h) and MA (90 µg/h) were added during the treatment periods for analysis of proximal tubular Na+ handling, plasma aldosterone and arginine vasopressin in male Sprague-Dawley rats. Results: Intravenous infusion of PH-MA (22 µg/h) and MA (90 µg/h) significantly (p ˂ .05) increased Na+ output, fractional excretion of Na+ (FENa) and lithium (FELi). Interestingly, like MA, PH-MA significantly (p ˂ .05) increased glomerular filtration rate (GFR) over the treatment period and decreased plasma aldosterone levels. Our findings indicate that PH-MA inhibited sodium reabsorption in the proximal and distal tubule as shown by increased FENa and low plasma aldosterone levels, respectively. Conclusions: PH-MA is, therefore, a promising multitarget antidiabetic agent that may ameliorate kidney function of diabetic patients at a dose four times lower than the parent compound (MA).

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