Could nephrotoxicity due to colistin be ameliorated with the use of N-acetylcysteine?

Özyılmaz, Ezgi; Ebinç, Fatma Ayerden; Derici, Ülver; Gülbahar, Özlem; Goktas, Guleser; Elmas, Çiğdem; Oğuzülgen, I. Kıvılcım; Sindel, Şükrü

doi:10.1007/s00134-010-2038-7

Cited by 70 publications

(59 citation statements)

References 17 publications

(8 reference statements)

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“…*, P Ͻ 0.05; **, P Ͻ 0.01 (compared to the control group); #, P Ͻ 0.05; ##, P Ͻ 0.01 (compared to the colistin group). [16][17][18]55). Increased production of ROS is an important mechanism in colistin-induced nephrotoxicity and neurotoxicity (17,(56)(57)(58).…”

Section: Discussionmentioning

confidence: 99%

Lycopene Attenuates Colistin-Induced Nephrotoxicity in Mice via Activation of the Nrf2/HO-1 Pathway

Dai

Tang

Deng

et al. 2015

Antimicrob Agents Chemother

103

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bNephrotoxicity is the major dose-limiting factor for the clinical use of colistin against multidrug-resistant (MDR) Gram-negative bacteria. This study aimed to investigate the protective effect of lycopene on colistin-induced nephrotoxicity in a mouse model. Fifty mice were randomly divided into 5 groups: the control group (saline solution), the lycopene group (20 mg/kg of body weight/day administered orally), the colistin group (15 mg/kg/day administered intravenously), the colistin (15 mg/kg/day) plus lycopene (5 mg/kg/day) group, and the colistin (15 mg/kg/day) plus lycopene (20 mg/kg/day) group; all mice were treated for 7 days. At 12 h after the last dose, blood was collected for measurements of blood urea nitrogen (BUN) and serum creatinine levels. The kidney tissue samples were obtained for examination of biomarkers of oxidative stress and apoptosis, histopathological assessment, and quantitative reverse transcription-PCR (qRT-PCR) analysis. Colistin treatment significantly increased concentrations of BUN and serum creatinine, tubular apoptosis/necrosis, lipid peroxidation, and heme oxygenase 1 (HO-1) activity, while the treatment decreased the levels of endogenous antioxidant biomarkers glutathione (GSH), catalase (CAT), and superoxide dismutase (SOD). Notably, the changes in the levels of all biomarkers were attenuated in the kidneys of mice treated with colistin by lycopene (5 or 20 mg/kg). Lycopene treatment, especially in the colistin plus lycopene (20 mg/kg) group, significantly downregulated the expression of NF-B mRNA (P < 0.01) but upregulated the expression of nuclear factor erythroid 2-related factor 2 (Nrf2) and HO-1 mRNA (both P < 0.01) in the kidney compared with the results seen with the colistin group. Our data demonstrated that coadministration of 20 mg/kg/day lycopene can protect against colistin-induced nephrotoxicity in mice. This effect may be attributed to the antioxidative property of lycopene and its ability to activate the Nrf2/HO-1 pathway.

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Section: Discussionmentioning

confidence: 99%

Lycopene Attenuates Colistin-Induced Nephrotoxicity in Mice via Activation of the Nrf2/HO-1 Pathway

Dai

Tang

Deng

et al. 2015

Antimicrob Agents Chemother

103

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“…Nephrotoxicity is usually reversible but can sometimes result in chronic kidney disease (CKD) [6]. Oxidative stress plays an important role in the pathogenesis of COL-induced nephrotoxicity so the protective effects of antioxidative agents, such as ascorbic acid, lycopene, and N-acetylcysteine [NAC] have been investigated recently [2,7,8]. NAC is commonly used as a mucolytic agent, but it has powerful anti-inflammatory and antioxidant activities [9].…”

Section: Introductionmentioning

confidence: 99%

“…The protective effect of NAC against oxidative stress has been demonstrated in different types of conditions, such as sepsis, chronic obstructive pulmonary disease (COPD), and contrastinduced nephropathy [10][11][12]. Beneficial effects of NAC, in terms of the resolution of renal injury, have also been demonstrated [8]. Our aim was to perform a retrospective cohort analysis to evaluate the role of adjunctive therapy with NAC in reducing the risk of COL-induced nephrotoxicity.…”

Section: Introductionmentioning

confidence: 99%

Colistin-induced nephrotoxicity and the role of N-acetylcysteine: a retrospective cohort study

Bozkurt

Sharma

Esen

2017

J Infect Dev Ctries

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Introduction: Colistin is associated with dose-dependent nephrotoxicity. N-acetylcycteine (NAC) may reduce the risk of concomitant acute kidney injury (AKI) due to its antioxidant properties. We report a retrospective cohort study evaluating the role of N-acetylcysteine (NAC) in the development of colistin (COL) associated nephrotoxicity. Methodology: A single centre retrospective cohort study was conducted in a university hospital between January 2014 and June 2015. Nephrotoxicity was defined and staged per the RIFLE (Risk, Injury, Failure, Loss of kidney function, and End-stage kidney disease) criteria. We evaluated the association between NAC use and COL-related nephrotoxicity by comparing the incidence of nephrotoxicity in patients receiving colistin with or without adjunctive NAC. Results: Forty-six patients received intravenous (IV) COL and 46 patients received IV NAC+COL. The cumulative COL doses did not differ between the two groups (p = 0.802). The initial creatinine value doubled in 29 (63%) patients undergoing NAC+COL therapy and in 27 (58.7%) patients in the COL group (p = 0.669). The median doubling time of baseline creatinine was 6 and 7 days in the NAC+COL and COL groups, respectively. The mean hospital stay, potentially nephrotoxic agent use, and mortality rates were statistically higher for the patients receiving NAC+COL (p < 0.005). Conclusions: The present study was not able to reveal any beneficial effect of NAC for patients undergoing COL therapy. The NAC+COL group had a higher baseline risk for development of AKI. However, the incidence of AKI was comparable between the groups. The results of the study would not solely exhibit the protective effect of adjunctive NAC therapy.

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“…It is not known why the nephroprotective effect of melatonin against these drugs has not been examined clinically. A recent study in rats (37) reported that coadministration of N-acetylcysteine seemed to ameliorate CMS-induced oxidative stress in kidney cells; however, the daily dose of the prodrug, CMS, was very low based upon animal scaling considerations (48), and no differences in histological abnormalities were observed between groups, including the CMS group. Our study is the first to demonstrate the protective effect of melatonin against colistin-induced nephrotoxicity.…”

mentioning

confidence: 98%

Melatonin Attenuates Colistin-Induced Nephrotoxicity in Rats

Yousef

Chen

Hill

et al. 2011

Antimicrob Agents Chemother

111

113

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Colistin-induced nephrotoxicity is a dose-limiting adverse effect when colistin is used against Gram-negative pathogens. This study examined the nephroprotective effect of melatonin against colistin in rats. Rats (n ‫؍‬ 7 per group) were treated intravenously twice daily with saline, colistin (at increasing doses from 0.5 to 4.0 mg/kg), melatonin (5 mg/kg), or both melatonin and colistin for 7 days. The severity of renal alteration was examined both biochemically and histologically. The effect of coadministration of melatonin on colistin pharmacokinetics was investigated. Significantly lower urinary N-acetyl-␤-D-glucosaminidase excretion was observed from day 1 in the colistin-melatonin group compared to the colistin group (P < 0.0001). Plasma creatinine increased significantly (P ‫؍‬ 0.023) only in the colistin group on day 6. Significant histological abnormalities (P < 0.0001) were detected only in the kidneys of the colistin group. Melatonin altered colistin pharmacokinetics; the total body clearance in the colistin-melatonin group (1.82 ؎ 0.26 ml/min/kg) was lower than in the colistin group (4.28 ؎ 0.93 ml/min/kg). This is the first study demonstrating the protective effect of melatonin against colistin-induced nephrotoxicity, which indicates that colistin-induced nephrotoxicity is mediated through oxidative stress. It also highlights the potential of coadministering an antioxidant to widen the therapeutic window of this very important last-line antibiotic.

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Could nephrotoxicity due to colistin be ameliorated with the use of N-acetylcysteine?

Abstract: Colistin-induced renal toxicity may be attributable to oxidative damage. The combined treatment of colistin plus NAC seems to have a beneficial role in restoration of the oxidant injury which may be related to its antioxidant effect.

Cited by 70 publications

References 17 publications

Lycopene Attenuates Colistin-Induced Nephrotoxicity in Mice via Activation of the Nrf2/HO-1 Pathway

Lycopene Attenuates Colistin-Induced Nephrotoxicity in Mice via Activation of the Nrf2/HO-1 Pathway

Colistin-induced nephrotoxicity and the role of N-acetylcysteine: a retrospective cohort study

Melatonin Attenuates Colistin-Induced Nephrotoxicity in Rats

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