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Effect of Ulinastatin against human renal tubular epithelial cell injury induced by gentamicin |
YE Tingting1 SHEN Jianming1 DENG Yanyan1 LIU Huihui1 YUAN Shenping2 |
1.Department of Nephrology, Renmin Hospital of Shiyan (People′s Hospital Affiliated to Hubei University of Medicine), Hubei Province, Shiyan 442000, China; 2.Department of Nephrology, Yunxi People′s Hospital, Hubei Province, Yunxi 442600, China |
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Abstract Objective To explore the effect of Ulinastatin (UTI) against human renal tubular epithelial cells (HK-2) injury and the probable mechanism by Gentamicin-induced. Methods HK-2 were cultured in vitro and divided into Sham group, Control group, UTI group A, B and C. Sham group does nothing, Control group and UTI group were added to Gentamicin, moreover UTI group were respectively added to different doses of UTI. The cell proliferation ability, the content of lactate dehydrogenase (LDH) and malondialdehyde (MDA), the activity of superoxide dismutase (SOD), the level of vascular cell adhesion molecule (VCAM)-1, monocyte chemoattractant protein (MCP)-1, tumor necrosis factor (TNF)-α, apoptosis rate, the express of Bcl-2 mRNA and Bax mRNA were detected. Results The cell proliferation ability and the activity of SOD in Control group were lower than those in Sham group, while the content of LDH and MDA, the levels of VCAM-1, MCP-1 and TNF-α in Control group were higher than those in Sham group, moreover apoptosis rate, and the express of Bcl-2 mRNA and Bax mRNA in Control group were higher than those in Sham group, and the differences were statistically significant (P < 0.05). The cell proliferation ability and the activity of SOD in UTI groups were higher than those in Control group, and the contents of LDH and MDA, the levels of VCAM-1, MCP-1 and TNF-α in UTI groups were lower than those in Control group, while apoptosis rate, and the expression of Bax mRNA in UTI groups were lower than those in Control group, and the expression of Bcl-2 mRNA in UTI groups was higher than that in Control group, and the differences were statistically significant (P < 0.05). Furthermore, there was a dose-response relationship (P < 0.05). Conclusion UTI can reduce Gentamicin-induced HK-2 injury by reducing oxidative stress, antagonizing inflammatory responses and inhibiting apoptosis.
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[1] Jenkins A,Thomson AH,Brown NM,et al. Amikacin use and therapeutic drug monitoring in adults: do dose regimens and drug exposures affect either outcome or adverse events?A systematic review [J]. J Antimicrob Chemother,2016,71(10):2754-2759.
[2] Eyler RF,Shvets K. Clinical Pharmacology of Antibiotics [J]. Clin J Am Soc Nephrol,2019,14(7):1080-1090.
[3] Mohamadi Yarijani Z,Najafi H,Shackebaei D,et al. Amelioration of renal and hepatic function,oxidative stress,inflammation and histopathologic damages by Malva sylvestris extract in gentamicin induced renal toxicity [J]. Biomed Pharmacother,2019,112:108 635.
[4] He F,Song Y,Ying WJ,et al. Effects of Ulinastatin on myocardial oxidative stress and inflammation in severely burned rats [J]. Eur Rev Med Pharmacol Sci,2018,22(17):5719-5728.
[5] Wang Y,Peng C,Zhang Z,et al. Intravenous infusion of ulinastatin attenuates acute kidney injury after cold ischemia/reperfusion [J]. Int Urol Nephrol,2019,51(10):1873-1881.
[6] 席加喜,张华君,陈晓宇.丹参酮ⅡA对万古霉素损伤HK-2细胞凋亡的影响及其机制的研究[J].中国医药导报,2018,15(11):8-11.
[7] 肖聪,张懿敏,孙圣荣.华蟾素联用顺铂对乳腺癌MDA-MB-231细胞活力、凋亡及周期分布的影响[J].中国医药导报,2019,16(21):12-16.
[8] Bayomy NA,Elbakary RH,Ibrahim MAA,et al. Effect of Lycopene and Rosmarinic Acid on Gentamicin Induced Renal Cortical Oxidative Stress,Apoptosis,and Autophagy in Adult Male Albino Rat [J]. Anat Rec(Hoboken),2017, 300(6):1137-1149.
[9] Luo QH,Chen ML,Chen ZL,et al. Evaluation of kim-1 and ngal as early indicators for assessment of gentamycin-induced nephrotoxicity in vivo and in vitro [J]. Kidney Blood Press Res,2016,41(6):911-918.
[10] Campos MAA,de Almeida LA,Grossi MF,et al. In vitro evaluation of biomarkers of nephrotoxicity through gene expression using gentamicin [J]. J Biochem Mol Toxicol,2018,32(9):e22 189.
[11] Galal HM,Abd EI-Rady NM. Aqueous garlic extract supresses experimental gentamicin induced renal pathophysiology mediated by oxidative stress,inflammation and Kim-1 [J]. Pathophysiology,2019,pii:S0928-4680(18)30332-8.
[12] Cao L,Zhi D,Han J,et al. Combinational effect of curcumin and metformin against gentamicin-induced nephrotoxicity:Involvement of antioxidative,anti-inflammatory and antiapoptotic pathway [J]. J Food Biochem,2019,43(7):e12 836.
[13] Helal MG,Zaki MMAF,Said E. Nephroprotective effect of saxagliptin against gentamicin-induced nephrotoxicity,emphasis on anti-oxidant,anti-inflammatory and anti-apoptic effects [J]. Life Sci,2018,208:64-71.
[14] 祁俊,吴杨炀.持续性血液净化联合乌司他丁治疗对烧伤并发脓毒症患者肺脏及肾脏功能的影响[J].中国医药导报,2019,16(1):82-85.
[15] Atal SS,Atal S. Ulinastatin-a newer potential therapeutic option for multiple organ dysfunction syndrome [J]. J Basic Clin Physiol Pharmacol,2016,27(2):91-99.
[16] Wan X,Xie X,Gendoo Y,et al. Ulinastatin administration is associated with a lower incidence of acute kidney injury after cardiac surgery: a propensity score matched study [J]. Crit Care,2016,20:42.
[17] Liu Q,Peng J,Zhou Y,et al. Clinical observation of ulinastatin combined with CRRT in the treatment of early cardiopulmonary resuscitation [J]. Exp Ther Med,2017, 14(6):6064-6068.
[18] Zhang QF. Ulinastatin inhibits renal tubular epithelial apoptosis and interstitial fibrosis in rats with unilateral ureteral obstruction [J]. Mol Med Rep,2017,16(6):8916-8922.
[19] Jiang GT,Chen X,Li D,et al. Ulinastatin attenuates renal interstitial inflammation and inhibits fibrosis progression in rats under unilateral ureteral obstruction [J]. Mol Med Rep,2014,10(3):1501-1508.
[20] 佘兴蓉,洪广亮,谭佳平,等.乌司他丁对百草枯诱导HK-2细胞损伤的保护作用及机制[J].中华劳动卫生职业病杂志,2015,33(7):501-506. |
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