Oxymatrine Alleviates Gentamicin-Induced Renal Injury in Rats

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....

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Main Authors: Songyao Kang, Tingting Chen, Zhihui Hao, Xiao Yang, Mingfa Wang, Zhifang Zhang, Sijia Hao, Fengting Lang, Hongxia Hao
Format: Article
Language:English
Published: MDPI AG 2022-09-01
Series:Molecules
Subjects:
Online Access:https://www.mdpi.com/1420-3049/27/19/6209
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author Songyao Kang
Tingting Chen
Zhihui Hao
Xiao Yang
Mingfa Wang
Zhifang Zhang
Sijia Hao
Fengting Lang
Hongxia Hao
author_facet Songyao Kang
Tingting Chen
Zhihui Hao
Xiao Yang
Mingfa Wang
Zhifang Zhang
Sijia Hao
Fengting Lang
Hongxia Hao
author_sort Songyao Kang
collection DOAJ
description 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 (<i>n</i> = 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 (<i>N</i>-acetyl-beta-<span style="font-variant: small-caps;">d</span>-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-κB 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.
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spelling doaj.art-312aa77eca7e49068e12e142d19907902023-11-23T21:07:26ZengMDPI AGMolecules1420-30492022-09-012719620910.3390/molecules27196209Oxymatrine Alleviates Gentamicin-Induced Renal Injury in RatsSongyao Kang0Tingting Chen1Zhihui Hao2Xiao Yang3Mingfa Wang4Zhifang Zhang5Sijia Hao6Fengting Lang7Hongxia Hao8Chinese Veterinary Medicine Innovation Center, College of Veterinary Medicine, China Agricultural University, Beijing 100193, ChinaChinese Veterinary Medicine Innovation Center, College of Veterinary Medicine, China Agricultural University, Beijing 100193, ChinaChinese Veterinary Medicine Innovation Center, College of Veterinary Medicine, China Agricultural University, Beijing 100193, ChinaChinese Veterinary Medicine Innovation Center, College of Veterinary Medicine, China Agricultural University, Beijing 100193, ChinaQingdao University Medical Group Juxian Hospital, Qingdao 276599, ChinaCollege of Traditional Medicine, Inner Mongolia Medical University, Hohhot 010059, ChinaCollege of Traditional Medicine, Inner Mongolia Medical University, Hohhot 010059, ChinaChinese Veterinary Medicine Innovation Center, College of Veterinary Medicine, China Agricultural University, Beijing 100193, ChinaChinese Veterinary Medicine Innovation Center, College of Veterinary Medicine, China Agricultural University, Beijing 100193, ChinaGentamicin 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 (<i>n</i> = 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 (<i>N</i>-acetyl-beta-<span style="font-variant: small-caps;">d</span>-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-κB 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.https://www.mdpi.com/1420-3049/27/19/6209gentamicinnephrotoxicityoxymatrineoxidative stressNrf2/HO-1
spellingShingle Songyao Kang
Tingting Chen
Zhihui Hao
Xiao Yang
Mingfa Wang
Zhifang Zhang
Sijia Hao
Fengting Lang
Hongxia Hao
Oxymatrine Alleviates Gentamicin-Induced Renal Injury in Rats
Molecules
gentamicin
nephrotoxicity
oxymatrine
oxidative stress
Nrf2/HO-1
title Oxymatrine Alleviates Gentamicin-Induced Renal Injury in Rats
title_full Oxymatrine Alleviates Gentamicin-Induced Renal Injury in Rats
title_fullStr Oxymatrine Alleviates Gentamicin-Induced Renal Injury in Rats
title_full_unstemmed Oxymatrine Alleviates Gentamicin-Induced Renal Injury in Rats
title_short Oxymatrine Alleviates Gentamicin-Induced Renal Injury in Rats
title_sort oxymatrine alleviates gentamicin induced renal injury in rats
topic gentamicin
nephrotoxicity
oxymatrine
oxidative stress
Nrf2/HO-1
url https://www.mdpi.com/1420-3049/27/19/6209
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