Protective effects of bendazac lysine against development of diabetic nephropathy

Abstract

Abstract: AIM: To investigate the protective effects of bendazac lysine (BDL) on diabetic nephropathy (DN) in vitro and in vivo experiments. METHODS: After rat mesangial cells were cultured in 3 concentrations of BDL for 36 h, the percentages of S phase of cells were determined by flowcytometry ;the transforming growth factor β₁(TGF-β₁ ) mRNA level was assayed by reverse transcription PCR;and two main components of extracellular matrix (ECM) , collagen Ⅳ and laminin, were determined by radioimmunoassay. Streptozotocin (STZ) induced diabetic rats were administered BDL at doses of 100, 200, 400 mg/kg for 8 weeks. The physical behavior andHbAlC levels of rats were observed. RESULTS: In the presence of high glucose and H₂O₂ , the percentages of S phase of cells were lowered, and TGF-β₁ mRNA level, collagen Ⅳ and laminin level were significantly increased. When compared with those in the high glucose group, the percentages of S phase of cells were significantly raised, and the levels of TGF-β₁mRNA, collagen Ⅳ and laminin were statistically decreased. The physical behavior of high BDL treated rats restored to be vibrant, vigorous and weight gaining, and the HbAlC level was significantly reduced. CONCLUSION: BDL has the protective effects against damage caused by DN, and is a potential drug candidate worth further study in preventing and treating DN.

Key words: bendazac lysine, diabetic nephropathy, mesangial cells, rats

CLC Number:

R965.2

YIN Xiao-xing, ZHANG Yin-di, YU Jun-xian, ZHANG Bei, SHEN Jian-ping, QIU Jun. Protective effects of bendazac lysine against development of diabetic nephropathy[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2007, 12(5): 552-561.

References

1 Cooper ME, Gilbert RE, EpsteinM.Pathophysiology of diabetic nephropathy[J].Metabolism, 1998;47:3-6.
2 Iglesias-De La Cruz MC, Ruiz-Torres P, Alcami J, et al.Hydrogen peroxide increases extracellular matrix mRNA through TGF-β in human mesangial cells[J].Kidney Int, 2001;59:87-95.
3 Oates PJ, Mylari BL.Aldose reductase inhibitors:therapeutic implications for diabetic complications[J].Expert Opin Investig Drugs, 1999 ;8:2095-2119.
4 Ishii H, Tada H, Isogai S.An aldose reductase inhibitor prevents glucose-induced increase in transforming growth factor-beta and protein kinase C activity in cultured human mesangial cells [J].Dialectologia, 1998 ;41:362-364.
5 Heidland A, Sebekova K, Schinzel R.Advanced glycation end products and the progressive course of renal disease[J].Am J Kidney Dis, 2001 ;38:S100-S106.
6 Kelly DJ, Cox AJ, TolcosM, et al.Attenuation of tubular apoptosis by blockade of the renin-angiotensin sy stem in diabetic Ren-2 rats[J].Kidney Int, 2002;61:31-39.
7 Haralson MA, Jacobson HR, Hoover RL.Collagen polymorphism in cultured rat kidney mesangial cells[J].Lab Invest, 1987;57:513-523.
8 Ardaillou N, Bellon G, Nivez MP, et al.Quantification of collagen synthesis by cultured human glomerular cells[J].Biochem Biophys Acta, 1989 ;991:445-452.
9 Ausiello DA, Kreisberg JI, Roy C, et al.Contraction of cultured rat glomerular cells of apparent mesangial origin after stimulation with angiotensin II and vasopression[J].J Clin Invest,1980;65:754-760.
10 Ayo SH, Radnik RA, Glass WF 2nd, et al.Increased extracellular matrix synthesis and mRNA in mesangial cells grown in high-glucose medium[J].Am J Physiol, 1991;260:F185-F191.
11 Balfour JA, Clissold SP, Bendazac ly sin.A review of its pharmacological properties and therapeutic potential in the management of cataracts[J].Drugs, 1990;39:575-596.
12 Yin XX, Zhang YD, Wu HW, et al.Protective effects of bendazac lysine on early experimental diabetic nephropathy rats[J]. Acta Pharmacol Sin, 2005;26:721-728.
13 Miller NJ, Rice-Evans C, Davies MJ, et al.A novel method for measuring antioxidant capacity and its application to monitoring the antioxidant status in premature neonates[J].Clin Sci,1993 ;84:407-412.
14 Yu L, Qiu HX, Chen WY, et al.The relationship between advanced glycosylation end products and the extracellular matrix of aorta in diabetic rats[J].Chin J Arteriosclerosis, 1999;7:311-314.
15 Shankland SJ, Scholey JW, Ly H, et al.Expression of transforming growth factor-beta 1 during diabetic renal hypertrophy [J].Kidney Int, 1994;46:430-442.
16 Wolf G.Cell cycle regulation in diabetic nephropathy[J].Kidney Int Suppl, 2000;7:S59-66.
17 Jandeleit-Dahm K, Cao Z, Cox AJ, et al.Role of hyperlipidemia in progressive renal disease:focus on diabetic nephropathy[J].Kidney Int Suppl, 1999 ;71:S31-S36.
18 Montero A, Munger KA, Khan RZ, et al.F( 2)-isoprostanes mediate high glucose-induced TGF-beta synthesis and glomerular proteinuria in experimental type Ⅰ diabetes[J].Kidney Int,2000 ;58:1963-1972.
19 汪建云, 印晓星.糖尿病肾病中转化生长因子-β1 信号转导与肾纤维化[J].中国临床药理学与治疗学, 2005;10:371-377.
20 KalousovaM, Zima T, Tesar V, et al.Advanced glycation end products in clinical nephrology[J].Kidney Blood Press Res, 2004 ;27:18-28.
21 Schmut O, Fellinger C, Hofmann H.Bendazac lysine:a protective substance against oxygen-free radicals.Recent developments in the pharmacological treatment of cataract[S].KuglerPublications Amsterdam, 1987;69-72.
22 Musci G., Silvestrini B.Mechanism of the scavenger-like activity of bendazac[J].Drugs Exp Clin Res, 1987;13:289-292.

[1]	WANG Donghui, JIANG Suwen, HU Airong, ZHU Bo, HE Zheyun, ZHANG Lukan, WANG Jialan, FAN Ying, LIN Ken . Mulberry exerts antioxidant stress effect in rats with nonalcoholic fatty liver disease [J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2023, 28(6): 609-616.
[2]	HENG Bingbing, YANG Danfeng, DAI Shuyang, SHANGGUAN Wangning. Propofol relieves the subcutaneous chloroquine-induced pruritus in rats via TRPV1 and CB1 receptors of spinal cord [J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2023, 28(10): 1101-1108.
[3]	JIN Yiyi, ZHOU Keting, YANG Chengcheng, XU Ping, ZHU Suyan. Osthole attenuates diabetes-induced renal injury by regulating NF-κB and p38/MAPK pathway mediated inflammatory responses [J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2022, 27(6): 622-631.
[4]	LEI Jing, HE Ping, CAI Wenlin, ZHANG Yongzhe, ZHANG Beiru, LIU Dajun. Cordyceps sinensis extracts attenuates HBx-induced mesangial cell proliferation and extracellular matrix synthesis by suppression of the PI3K/Akt pathways [J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2022, 27(11): 1247-1254.
[5]	WU Wei, CHEN Zheng, DU Zhen, QU Shuangquan. Vinpocetine improves the long-term cognitive function of infant rats induced by sevoflurane via Wnt/GSK3β/β-catenin signaling pathway [J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2021, 26(5): 539-545.
[6]	LIU Peng, ZHAO Hailing, SHEN Zhengri, WANG Chen, WANG Yun, QIU Xinping, LI Ping. Tangshen formula promotes cellular cholesterol efflux in HG-induced mTECs by suppression of TGF-β1/Smad3 pathway [J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2021, 26(1): 1-9.
[7]	GAO Yiwen, ZHANG Nan, LV Chanmei, YANG Xuanmei, YUE Guihua. Effects of Huanglianjiedu Decoction on vascular endothelial NO pathway in young spontaneously hypertensive rats [J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2019, 24(3): 248-253.
[8]	ZHAO Shaojing, ZENG Yan, LI Zhengdong, ZHANG Hua. Protective effects of L-carnitine on diabetic nephropathy in rats [J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2019, 24(3): 278-282.
[9]	ZHANG Heng, WU Haixiao, HU Yang, YANG Qing, HUANG Ting. Study on the improvement of PI3K/AKT pathway in diabetic rats with neurogenic bladder disease by extract of semen plantannical [J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2019, 24(11): 1249-1255.
[10]	WANG Rouxin, FANG Zekang, YAO Siqi, XUE Yingying, ZHAO Yeying, YE Yilu. Effects of nicotinamide ribose on adolescent depression rats after neonatal maternal deprivation [J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2018, 23(9): 1015-1021.
[11]	YAO Xinming, KONG Xiang, ZHAO Yongli, HUA Qiang, HE Chunling, YU Dan, LI Yeqiong, DAI Xiaokang, YE Shandong. Metformin inhibits p38MAPK signaling pathway and oxidativestress in rat glomerular mesangial cells cultured with high glucose [J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2018, 23(6): 614-620.
[12]	HAO Shaojun, MA Junjie, KONG Xuejun, SU Feng, LI Jun, LI Wenjun, ZHANG Zhengchen. Effects of compound Cotinus coggygria oral liquid on liver homogenate and liver tissue of rats [J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2018, 23(6): 627-631.
[13]	CHENG Xiaolong, HU Kunmei, HU Haoran，XU Hanghang, YANG Jieren, HAN Jun. Effects of Chinese medicine Yuxia capsule on renal fibrosis in spontaneously hypertensive rats [J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2018, 23(6): 632-639.
[14]	YAO Jia, QIAO Di, GUO Xin, CUI Changmeng. Therapeutic effects of 1-Deoxynojirimycin in mulberry leaves on rats with diabetic nephropathy [J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2018, 23(5): 517-523.
[15]	JIANG Lili, MAO Limin, HU Sijia, PENG Yingzhi. Effects of Shenshuaining granules on the expression of NF-kB and PPAR-gamma in kidney tissue of diabetic nephropathy rats [J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2018, 23(2): 132-137.