Oxymatrine Alleviates Gentamicin-Induced Renal Injury in Rats

被引:26
作者
Kang, Songyao [1 ,2 ]
Chen, Tingting [1 ]
Hao, Zhihui [1 ]
Yang, Xiao [1 ]
Wang, Mingfa [3 ]
Zhang, Zhifang [4 ]
Hao, Sijia [4 ]
Lang, Fengting [1 ,2 ]
Hao, Hongxia [1 ,2 ]
机构
[1] China Agr Univ, Coll Vet Med, Chinese Vet Med Innovat Ctr, Beijing 100193, Peoples R China
[2] Qingdao Agr Univ, Agr Biopharmaceut Engn Technol Res Ctr, Qingdao 266109, Peoples R China
[3] Qingdao Univ Med Grp, Juxian Hosp, Qingdao 276599, Peoples R China
[4] Inner Mongolia Med Univ, Coll Tradit Med, Hohhot 010059, Peoples R China
基金
中国国家自然科学基金;
关键词
gentamicin; nephrotoxicity; oxymatrine; oxidative stress; Nrf2; HO-1; NF-KAPPA-B; INDUCED NEPHROTOXICITY; INDUCED APOPTOSIS; OXIDATIVE STRESS; INFLAMMATION; DAMAGE; ANTIOXIDANT; INHIBITION; PATHWAY;
D O I
10.3390/molecules27196209
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Gentamicin is an aminoglycoside antibiotic commonly used to treat Gram-negative bacterial infections that possesses considerable nephrotoxicity. Oxymatrine is a phytochemical with the ability to counter gentamicin toxicity. We investigated the effects and protective mechanism of oxymatrine in rats. The experimental groups were as follows: Control, Oxymatrine only group (100 mg/kg/d), Gentamicin only group (100 mg/kg/d), Gentamicin (100 mg/kg/d) plus Oxymatrine (100 mg/kg/d) group (n = 10). All rats were treated for seven continuous days. The results indicated that oxymatrine alleviated gentamicin-induced kidney injury, and decreased rats' kidney indices and NAG (N-acetyl-beta-d-glucosaminidase), BUN (blood urea nitrogen) and CRE (creatine) serum levels. The oxymatrine-treated group sustained less histological damage. Oxymatrine also relived gentamicin-induced oxidative and nitrative stress, indicated by the increased SOD (superoxidase dismutase), GSH (glutathione) and CAT (catalase) activities and decreased MDA (malondialdehyde), iNOS (inducible nitric oxide synthase) and NO (nitric oxide) levels. Caspase-9 and -3 activities were also decreased in the oxymatrine-treated group. Oxymatrine exhibited a potent anti-inflammatory effect on gentamicin-induced kidney injury, down-regulated the Bcl-2ax and NF-kappa B mRNAs, and upregulated Bcl-2, HO-1 and Nrf2 mRNAs in the kidney tissue. Our investigation revealed the renal protective effect of oxymatrine in gentamicin-induced kidney injury for the first time. The effect was achieved through activation of the Nrf2/HO-1 pathways. The study underlines the potential clinical application of oxymatrine as a renal protectant agent for gentamicin therapy.
引用
收藏
页数:11
相关论文
共 36 条
[1]   Agents ameliorating or augmenting experimental gentamicin nephrotoxicity: some recent research [J].
Ali, BH .
FOOD AND CHEMICAL TOXICOLOGY, 2003, 41 (11) :1447-1452
[2]   Renoprotective effects of the direct renin inhibitor aliskiren on gentamicin-induced nephrotoxicity in rats [J].
Bae, Eun Hui ;
Kim, In Jin ;
Joo, Soo Yeon ;
Kim, Eun Young ;
Choi, Joon Seok ;
Kim, Chang Seong ;
Ma, Seong Kwon ;
Lee, JongUn ;
Kim, Soo Wan .
JOURNAL OF THE RENIN-ANGIOTENSIN-ALDOSTERONE SYSTEM, 2014, 15 (04) :348-361
[3]   Effects of pre and post-treatments with dipyridamole in gentamicininduced acute nephrotoxicity in the rat [J].
Balakumar, Pitchai ;
WitnessKoe, Wei Em ;
Gan, Yi Syen ;
JemayPuah, Soo Mei ;
Kuganesswari, Subramaniam ;
Prajapati, Sunil Kumar ;
Varatharajan, Rajavel ;
Jayachristy, Sam Annie ;
Sundram, Karupiah ;
Bahari, Mohd Baidi .
REGULATORY TOXICOLOGY AND PHARMACOLOGY, 2017, 84 :35-44
[4]   Attenuation of gentamicin-induced nephrotoxicity in rats by fleroxacin [J].
Beauchamp, D ;
Laurent, G ;
Grenier, L ;
Gourde, P ;
Zanen, J ;
HeusonStiennon, JA ;
Bergeron, MG .
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, 1997, 41 (06) :1237-1245
[5]   A small molecule inhibitor of tropomyosin dissociates actin binding from tropomyosin-directed regulation of actin dynamics [J].
Bonello, Teresa T. ;
Janco, Miro ;
Hook, Jeff ;
Byun, Alex ;
Appaduray, Mark ;
Dedova, Irina ;
Hitchcock-DeGregori, Sarah ;
Hardeman, Edna C. ;
Stehn, Justine R. ;
Boecking, Till ;
Gunning, Peter W. .
SCIENTIFIC REPORTS, 2016, 6
[6]   Efficiency of Sophora flavescens-Fructus Ligustri Lucidi Drug Pairs in the Treatment of Liver Fibrosis Based on the Response Surface Method [J].
Chu, Shuhan ;
Zhang, Hongxu ;
Ding, Lixin .
EVIDENCE-BASED COMPLEMENTARY AND ALTERNATIVE MEDICINE, 2019, 2019
[7]   Reactive oxygen species, cellular redox systems, and apoptosis [J].
Circu, Magdalena L. ;
Aw, Tak Yee .
FREE RADICAL BIOLOGY AND MEDICINE, 2010, 48 (06) :749-762
[8]   Chloroquine ameliorates carbon tetrachloride-induced acute liver injury in mice via the concomitant inhibition of inflammation and induction of apoptosis [J].
Dai, Chongshan ;
Xiao, Xilong ;
Li, Daowen ;
Tun, Sun ;
Wang, Ying ;
Velkov, Tony ;
Tang, Shusheng .
CELL DEATH & DISEASE, 2018, 9
[9]   Gentamicin-induced apoptosis in renal cell lines and embryonic rat fibroblasts [J].
El Mouedden, M ;
Laurent, G ;
Mingeot-Leclercq, MP ;
Tulkens, PM .
TOXICOLOGICAL SCIENCES, 2000, 56 (01) :229-239
[10]   Carvedilol exacerbate gentamicin-induced kidney mitochondrial alterations in adult rat [J].
Felix, Luis ;
Oliveira, M. M. ;
Videira, Romeu ;
Maciel, Elisabete ;
Alves, Nuno D. ;
Nunes, Fernando M. ;
Alves, Anabela ;
Almeida, Jose M. ;
Domingues, M. Rosario M. ;
Peixoto, Francisco P. .
EXPERIMENTAL AND TOXICOLOGIC PATHOLOGY, 2017, 69 (02) :83-92