Protective effect of 3-n-butylphthalide against hypertensive nephropathy in spontaneously hypertensive rats

Zhu,Jun; Zhang,Yantao; Yang,Changhai

doi:10.3892/mmr.2014.2791

Protective effect of 3-n-butylphthalide against hypertensive nephropathy in spontaneously hypertensive rats

Authors:
- Jun Zhu
- Yantao Zhang
- Changhai Yang
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Affiliations: Department of Urology, Tianjin Medical University General Hospital, Tianjin 300052, P.R. China
Published online on: October 27, 2014 https://doi.org/10.3892/mmr.2014.2791
Pages: 1448-1454

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Abstract

Previous studies have demonstrated that a natural product of celery seeds, 3‑n‑butylphthalide (NBP), has significant antihypertensive effects that are widely utilized in Chinese traditional medicine. The present study aimed to investigate the effects of NBP on hypertensive nephropathy, as well as the mechanisms underlying this disease in spontaneously hypertensive rats (SHRs). SHRs were treated orally with saline, NBP (15 or 30 mg/kg) or losartan (10 mg/kg) daily for 20 weeks, during which time blood pressure was measured every four weeks. At the end of the 20‑week treatment, blood and urine samples were collected for biochemical analysis, and kidney tissues were obtained for histopathological analysis and immunohistochemistry. Enzyme‑linked immunosorbent assays and western blotting were used to analyze the expression of transforming growth factor (TGF)‑β1 in blood and kidney tissues, respectively. The results showed that NBP effectively attenuated progression of hypertensive nephropathy by decreasing urinary albumin excretion and blood urea nitrogen levels. It significantly decreased blood pressure (although less markedly than losartan) and the incidence of glomerulosclerosis. In addition, it alleviated tubular impairment and significantly decreased oxidative stress, as well as the expression of pro‑inflammatory cytokines and TGF‑β1 in kidney tissues. In conclusion, the results suggested that NBP may slow the progression of hypertensive nephropathy by a variety of mechanisms.

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1	Azegami T, Sasamura H, Hayashi K and Itoh H: Vaccination against the angiotensin type 1 receptor for the prevention of L-NAME-induced nephropathy. Hypertens Res. 35:492–499. 2012. View Article : Google Scholar
2	Hill GS: Hypertensive nephrosclerosis. Curr Opin Nephrol Hypertens. 17:266–270. 2008. View Article : Google Scholar : PubMed/NCBI
3	Zhang S, Li H, Li Y, et al: Nicousamide normalizes renovascular hypertension in two-kidney one-clip hypertensive rats. Biomed Rep. 1:89–92. 2013.PubMed/NCBI
4	Zhang S, Li Y, Li H, et al: Renal protective effect of nicousamide on hypertensive nephropathy in spontaneously hypertensive rats. Biomed Rep. 1:34–40. 2013.PubMed/NCBI
5	Iseki K: Factors influencing the development of end-stage renal disease. Clin Exp Nephrol. 9:5–14. 2005. View Article : Google Scholar : PubMed/NCBI
6	Klag MJ, Whelton PK, Randall BL, et al: Blood pressure and end-stage renal disease in men. N Engl J Med. 334:13–18. 1996. View Article : Google Scholar : PubMed/NCBI
7	Tozawa M, Iseki K, Iseki C, Kinjo K, Ikemiya Y and Takishita S: Blood pressure predicts risk of developing end-stage renal disease in men and women. Hypertension. 41:1341–1345. 2003. View Article : Google Scholar : PubMed/NCBI
8	Chen Y, Lipkowitz MS, Salem RM, et al: Progression of chronic kidney disease: Adrenergic genetic influence on glomerular filtration rate decline in hypertensive nephrosclerosis. Am J Nephrol. 32:23–30. 2010. View Article : Google Scholar : PubMed/NCBI
9	Wang G, Lai FM, Kwan BC, et al: Expression of ACE and ACE2 in patients with hypertensive nephrosclerosis. Kidney Blood Press Res. 34:141–149. 2011. View Article : Google Scholar : PubMed/NCBI
10	Moghadam MH, Imenshahidi M and Mohajeri SA: Antihypertensive effect of celery seed on rat blood pressure in chronic administration. J Med Food. 16:558–563. 2013. View Article : Google Scholar : PubMed/NCBI
11	Zhang L, Lü L, Chan WM, et al: Effects of DL-3-n-butylphthalide on vascular dementia and angiogenesis. Neurochem Res. 37:911–919. 2012. View Article : Google Scholar : PubMed/NCBI
12	Liao SJ, Lin JW, Pei Z, et al: Enhanced angiogenesis with dl-3n-butylphthalide treatment after focal cerebral ischemia in RHRSP. Brain Res. 1289:69–78. 2009. View Article : Google Scholar : PubMed/NCBI
13	Chong ZZ and Feng YP: dl-3-n-butylphthalide attenuates reperfusion-induced blood-brain barrier damage after focal cerebral ischemia in rats. Zhongguo Yao Li Xue Bao. 20:696–700. 1999.
14	Cui LY, Zhu YC, Gao S, et al: Ninety-day administration of dl-3-n-butylphthalide for acute ischemic stroke: a randomized, double-blind trial. Chinese Med J (Engl). 126:3405–3410. 2013.
15	Li L, Zhang B, Tao Y, et al: DL-3-n-butylphthalide protects endothelial cells against oxidative/nitrosative stress, mitochondrial damage and subsequent cell death after oxygen glucose deprivation in vitro. Brain Res. 1290:91–101. 2009. View Article : Google Scholar : PubMed/NCBI
16	Liu CL, Liao SJ, Zeng JS, et al: dl-3n-butylphthalide prevents stroke via improvement of cerebral microvessels in RHRSP. J Neurol Sci. 260:106–113. 2007. View Article : Google Scholar : PubMed/NCBI
17	Tian D, Ling S, Chen G, et al: Hypertensive nephropathy treatment by heart-protecting musk pill: a study of anti-inflammatory therapy for target organ damage of hypertension. Int J Gen Med. 4:131–139. 2011.PubMed/NCBI
18	Sun L, Ke Y, Zhu CY, et al: Inflammatory reaction versus endogenous peroxisome proliferator-activated receptors expression, re-exploring secondary organ complications of spontaneously hypertensive rats. Chin Med J (Engl). 121:2305–2311. 2008.
19	Koshikawa S, Nishikimi T, Inaba C, et al: Fasudil, a Rho-kinase inhibitor, reverses L-NAME exacerbated severe nephrosclerosis in spontaneously hypertensive rats. J Hypertens. 26:1837–1848. 2008. View Article : Google Scholar : PubMed/NCBI
20	Alfie J, Aparicio LS and Waisman GD: Current strategies to achieve further cardiac and renal protection through enhanced renin-angiotensin-aldosterone system inhibition. Rev Recent Clin Trials. 6:134–146. 2011. View Article : Google Scholar : PubMed/NCBI
21	Berl T: Review: renal protection by inhibition of the renin-angiotensin-aldosterone system. J Renin Angiotensin Aldosterone Syst. 10:1–8. 2009. View Article : Google Scholar : PubMed/NCBI
22	Zhang S, Xin H, Li Y, et al: Skimmin, a coumarin from Hydrangea paniculata, slows down the progression of membranous glomerulonephritis by anti-inflammatory effects and inhibiting immune complex deposition. Evid Based Complement Alternat Med. 8192962013.PubMed/NCBI
23	Tapia E, Sanchez-Lozada LG, Soto V, et al: Sildenafil treatment prevents glomerular hypertension and hyperfiltration in rats with renal ablation. Kidney Blood Press Res. 35:273–280. 2012. View Article : Google Scholar : PubMed/NCBI
24	Pörsti I, Fan M, Kööbi P, et al: High calcium diet down-regulates kidney angiotensin-converting enzyme in experimental renal failure. Kidney Int. 66:2155–2166. 2004. View Article : Google Scholar : PubMed/NCBI
25	Li P, Ma LL, Xie RJ, et al: Treatment of 5/6 nephrectomy rats with sulodexide: a novel therapy for chronic renal failure. Acta Pharmacol Sin. 33:644–651. 2012. View Article : Google Scholar : PubMed/NCBI
26	Giani JF, Muñoz MC, Pons RA, et al: Angiotensin-(1–7) reduces proteinuria and diminishes structural damage in renal tissue of stroke-prone spontaneously hypertensive rats. Am J Physiol Renal Physiol. 300:F272–F282. 2011. View Article : Google Scholar
27	Tomohiro T, Kumai T, Sato T, et al: Hypertension aggravates glomerular dysfunction with oxidative stress in a rat model of diabetic nephropathy. Life Sci. 80:1364–1372. 2007. View Article : Google Scholar : PubMed/NCBI
28	Li L, Yang R, Sun K, et al: Cerebroside-A provides potent neuroprotection after cerebral ischaemia through reducing glutamate release and Ca²⁺ influx of NMDA receptors. Int J Neuropsychopharmacol. 15:497–507. 2012. View Article : Google Scholar
29	Liu Y: Renal fibrosis: new insights into the pathogenesis and therapeutics. Kidney Int. 69:213–217. 2006. View Article : Google Scholar : PubMed/NCBI
30	Tomino Y, Hagiwara S and Gohda T: AGE-RAGE interaction and oxidative stress in obesity-related renal dysfunction. Kidney Int. 80:133–135. 2011. View Article : Google Scholar : PubMed/NCBI
31	Koyner JL, Sher Ali R and Murray PT: Antioxidants. Do they have a place in the prevention or therapy of acute kidney injury? Nephron Exp Nephrol. 109:e109–e117. 2008. View Article : Google Scholar : PubMed/NCBI
32	Semedo P, Correa-Costa M, Antonio Cenedeze M, et al: Mesenchymal stem cells attenuate renal fibrosis through immune modulation and remodeling properties in a rat remnant kidney model. Stem Cells. 27:3063–3073. 2009.PubMed/NCBI
33	Azuma H, Nadeau K, Takada M, Mackenzie HS and Tilney NL: Cellular and molecular predictors of chronic renal dysfunction after initial ischemia/reperfusion injury of a single kidney. Transplantation. 64:190–197. 1997. View Article : Google Scholar : PubMed/NCBI
34	Navarro-González JF and Mora-Fernández C: The role of inflammatory cytokines in diabetic nephropathy. J Am Soc Nephrol. 19:433–442. 2008. View Article : Google Scholar : PubMed/NCBI
35	Cervenka L and Heller J: Comparison of the effects of a low-protein diet with the effects of a converting enzyme inhibitor on the progression of renal insufficiency in hypertensive rats. Renal Fail. 18:173–180. 1996. View Article : Google Scholar