PMID- 30035652
OWN - NLM
STAT- MEDLINE
DCOM- 20181026
LR  - 20181114
IS  - 1525-6049 (Electronic)
IS  - 0886-022X (Print)
IS  - 0886-022X (Linking)
VI  - 40
IP  - 1
DP  - 2018 Nov
TI  - N-acetylcysteine suppresses colistimethate sodium-induced nephrotoxicity via 
      activation of SOD2, eNOS, and MMP3 protein expressions.
PG  - 423-434
LID - 10.1080/0886022X.2018.1489286 [doi]
AB  - OBJECTIVE: To investigate the molecular mechanisms of colistimethate 
      sodium-induced nephrotoxicity and the protective effect of N-acetylcysteine (NAC) 
      against nephrotoxicity. METHODS: Twenty-eight Wistar rats were divided into four 
      groups comprised of control, colistin, NAC, and colistin-NAC co-treatment, 
      respectively. Serum creatinine and urine N-acetyl-beta-d-glucosaminidase (NAG) 
      levels were measured at different time intervals. Histological changes, 
      apoptosis, total oxidant and antioxidant status, and the expression levels of 
      endothelial nitric oxide synthase (eNOS), superoxide dismutase 2 (SOD2), and 
      matrix metalloproteinase 3 (MMP3) were evaluated in renal tissue. RESULTS: In the 
      colistin group, post-treatment creatinine levels were higher than pretreatment 
      levels (p = .001). There was a significant increase in urine NAG level following 
      colistin treatment on day 10, compared to the baseline value and the first day of 
      treatment (p = .001 and .0001, respectively). Urine NAG levels were higher in the 
      colistin group on the 10th day of treatment than in the other groups (p < .01). 
      Colistin treatment increased the apoptosis index and renal histological damage 
      score (RHDS) significantly and these changes were reversed in NAC co-treatment 
      (RHSD and apoptosis index were 45 and 0 for sterile saline group, 29 and 2 for 
      NAC group, 122 and 7 for colistin group, and 66 and 2 for colistin + NAC group). 
      We observed no difference between groups regarding total antioxidant and total 
      oxidant status in the kidneys. The expression levels of eNOS, SOD2, and MMP3 
      decreased significantly in the kidneys of colistin-treated rats; these changes 
      were reversed in the kidneys of NAC co-treated rats. CONCLUSIONS: 
      N-acetylcysteine prevented colistin-induced nephrotoxicity through activation of 
      expression levels of SOD2, eNOS, and MMP3.
FAU - Ceylan, Bahadir
AU  - Ceylan B
AD  - a Department of Infectious Diseases and Clinical Microbiology, Faculty of 
      Medicine , Istanbul Medipol University , Istanbul , Turkey.
FAU - Ozansoy, Mehmet
AU  - Ozansoy M
AD  - b Department of Physiology, International School of Medicine , Istanbul Medipol 
      University , Istanbul , Turkey.
FAU - Kilic, Ulkan
AU  - Kilic U
AD  - c Department of Medical Biology, Faculty of Medicine , University of Health 
      Sciences , Istanbul , Turkey.
FAU - Yozgat, Yasemin
AU  - Yozgat Y
AD  - d Department of Medical Biology, Faculty of Medicine , Istanbul Medipol 
      University , Istanbul , Turkey.
FAU - Ercan, Cilem
AU  - Ercan C
AD  - e Department of Medical Biology, Faculty of Medicine , Bezmialem Vakif University 
      , Istanbul , Turkey.
FAU - Yildiz, Pelin
AU  - Yildiz P
AD  - f Department of Pathology, Faculty of Medicine , Bezmialem Vakif University , 
      Istanbul , Turkey.
FAU - Aslan, Turan
AU  - Aslan T
AD  - g Department of Infectious Diseases and Clinical Microbiology, Faculty of 
      Medicine , Bezmialem Vakif University , Istanbul , Turkey.
LA  - eng
PT  - Journal Article
PL  - England
TA  - Ren Fail
JT  - Renal failure
JID - 8701128
RN  - 0 (Free Radical Scavengers)
RN  - 0 (Reactive Oxygen Species)
RN  - AYI8EX34EU (Creatinine)
RN  - DL2R53P963 (colistinmethanesulfonic acid)
RN  - EC 1.14.13.39 (Nitric Oxide Synthase Type III)
RN  - EC 1.14.13.39 (Nos3 protein, rat)
RN  - EC 1.15.1.1 (Superoxide Dismutase)
RN  - EC 1.15.1.1 (superoxide dismutase 2)
RN  - EC 3.2.1.52 (Acetylglucosaminidase)
RN  - EC 3.4.24.17 (Matrix Metalloproteinase 3)
RN  - WYQ7N0BPYC (Acetylcysteine)
RN  - Z67X93HJG1 (Colistin)
SB  - IM
MH  - Acetylcysteine/*pharmacology/therapeutic use
MH  - Acetylglucosaminidase/blood
MH  - Acute Kidney Injury/blood/chemically induced/*drug therapy/pathology
MH  - Animals
MH  - Colistin/analogs & derivatives/toxicity
MH  - Creatinine/blood
MH  - Disease Models, Animal
MH  - Free Radical Scavengers/*pharmacology/therapeutic use
MH  - Humans
MH  - Kidney/drug effects/pathology
MH  - Male
MH  - Matrix Metalloproteinase 3/metabolism
MH  - Nitric Oxide Synthase Type III/metabolism
MH  - Rats
MH  - Rats, Wistar
MH  - Reactive Oxygen Species/metabolism
MH  - Superoxide Dismutase/metabolism
PMC - PMC6060374
OTO - NOTNLM
OT  - Antioxidant
OT  - colistin
OT  - nephrotoxicity
OT  - rat model
OT  - reactive oxygen species
EDAT- 2018/07/24 06:00
MHDA- 2018/10/27 06:00
PMCR- 2018/07/23
CRDT- 2018/07/24 06:00
PHST- 2018/07/24 06:00 [entrez]
PHST- 2018/07/24 06:00 [pubmed]
PHST- 2018/10/27 06:00 [medline]
PHST- 2018/07/23 00:00 [pmc-release]
AID - 1489286 [pii]
AID - 10.1080/0886022X.2018.1489286 [doi]
PST - ppublish
SO  - Ren Fail. 2018 Nov;40(1):423-434. doi: 10.1080/0886022X.2018.1489286.