The effects of Syzygium aromaticum-derived oleanolic acid on kidney function of male Sprague-Dawley rats and on kidney cell lines

Physiology 2012 (Edinburgh) (2012) Proc Physiol Soc 27, C37

Oral Communications: The effects of Syzygium aromaticum-derived oleanolic acid on kidney function of male Sprague-Dawley rats and on kidney cell lines

H. Madlala1, B. Masola2, M. Singh2, C. T. Musabayane1

1. Human Physiology, University of KwaZulu-Natal, Durban, KwaZulu-Natal, South Africa. 2. Biochemistry, University of KwaZulu-Natal, Durban, KwaZulu-Natal, South Africa.

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Studies indicate that Syzygium spp derived oleanolic acid (OA) enhances renal function of streptozotocin (STZ)-induced diabetic rats as evidenced by its reversal of the previously reported inability of the kidney to excrete Na+ in these animals1. Accordingly this study monitored renal fluid and electrolyte outputs in conscious male Sprague-Dawley administered with OA twice every third day for five weeks. The study also investigated the effects of OA on proximal tubular Na+ handling in rats fed standard rodent chow supplemented with lithium chloride (12 mmol kg-1 dry weight) for 48 h prior to experimentation in order to raise plasma lithium to measurable concentrations without affecting renal Na+ or water excretion2 in an effort to establish tubular effects of the triterpene. Thereafter, the animals were anaesthetized and the right jugular vein was cannulated to allow intravenous infusion of 0.077M NaCl. The urinary bladder was also cannulated via an incision in the lower abdomen. After a 3½ h equilibration period, urine samples were taken every 30 min over the 4h post-equilibration period of 1h control, 1h 30 min treatment and 1h 30 min recovery periods; blood samples were taken once per hour for the measurement of electrolyte and clearance marker concentrations. Li clearance is widely to assess proximal tubular function of the mammalian kidney3. Glomerular filtration rate (GFR) was assessed by creatinine clearance. Cytotoxicity of OA on kidney and liver cell lines was assessed by the MTT and comet assays. Statistical comparison of the differences between the control means and experimental groups was performed with GraphPad InStat Software (version 4.00, GraphPad Software, San Diego, California, USA), using one-way analysis of variance (ANOVA), followed by Tukey-Kramer multiple comparison test. A value of p<0.05 was considered significant. OA increased Na+ excretion of conscious male Sprague-Dawley rats from week 3 to week 5. By the end of the 5th week experimental period, OA treatment significantly reduced (p<0.05) plasma creatinine concentration of STZ-induced diabetic rats with a concomitant elevation in GFR. Acute OA infusion was also associated with increases in fractional excretion of sodium (FENa) and lithium (FELi) in anaesthetized rats in the absence of significant changes in GFR. The MTT assay studies demonstrated that OA increased the metabolic activity of kidney and liver cell lines. Taken together with previous observations that OA increases GFR in streptozotocin induced diabetic rats, this study implicates the proximal tubule in OA-evoked increases in urinary Na+ output. Key words: Renal function; diabetes mellitus; Syzygium aromaticum; oleanolic acid; triterpenes



Where applicable, experiments conform with Society ethical requirements.

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