PMID- 26823989
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20201001
IS  - 2155-6156 (Print)
IS  - 2155-6156 (Electronic)
VI  - 6
IP  - 6
DP  - 2015 Jun
TI  - Inhibition of 12/15-Lipoxygenase Reduces Renal Inflammation and Injury in 
      Streptozotocin-Induced Diabetic Mice.
LID - 555 [pii]
AB  - Previous studies suggest that 12/15 lipoxygenase (12/15-LO) is implicated in 
      diabetic vascular complications. We hypothesize that 12/15-LO inhibition 
      attenuates renal inflammation and injury in streptozotocin-induced diabetes. 
      Diabetes was induced in wild-type C57BL/6J (WT) and 12/15-LO deficient mice using 
      streptozotocin. Additionally, four groups of WT mice were also used; control non 
      diabetic, diabetic, diabetic treated with the 12/15-LO inhibitor baicalein for 10 
      weeks and diabetic treated with baicalein only for the last 4 weeks of the 
      experiment. After 10 weeks of induction of diabetes with streptozotocin, WT 
      diabetic mice exhibited marked elevation in proteinuria together with elevation 
      in the excretion levels of thiobarbituric acid reactive substance (TBARs), a 
      marker of oxidative stress, and monocyte chemoattractant protein-1 (MCP-1), a 
      marker of inflammation and these changes were significantly reduced in 12/15-LO 
      deficient diabetic mice (P<0.05). Similarly, pharmacological inhibition of 
      12/15-LO with baicalein prevented the elevation in renal 12-HETE production, the 
      major murine metabolic product of 12/15-LO, in diabetic mice, and this effect was 
      associated with decreased proteinuria, TBARs excretion and renal collagen 
      deposition compared to untreated diabetic mice. Interestingly, the protective 
      effects of baicalein were not noticed when only administered in the last 4 weeks 
      of diabetes compared to untreated diabetic mice. WT diabetic mice displayed 
      elevation in renal interleukin-6 (IL-6) levels and these changes were only 
      reduced in diabetic mice treated with baicalein for 10 weeks (P<0.05). The 
      anti-inflammatory effects of baicalein or 12/15-LO deficiency were further 
      confirmed in lipopolysaccharide (LPS)-induced acute renal inflammation as 
      inhibition of 12/15-LO reduced the elevation in renal soluble epoxide hydrolase 
      expression in LPS-injected mice. These results suggest that increased 12/15-LO 
      activity and 12-HETE production contribute to the elevation of renal oxidative 
      stress, inflammation and injury in streptozotocin-induced diabetic mice.
FAU - Faulkner, Jessica
AU  - Faulkner J
AD  - Department of Oral Biology, Georgia Regents University, Augusta, GA, USA.
FAU - Pye, Chelsey
AU  - Pye C
AD  - Department of Oral Biology, Georgia Regents University, Augusta, GA, USA.
FAU - Al-Shabrawey, Mohamed
AU  - Al-Shabrawey M
AD  - Department of Oral Biology, Georgia Regents University, Augusta, GA, USA; 
      Department of Ophthalmology and Culver Vision Discovery Institute, Georgia 
      Regents University, Augusta, GA, USA.
FAU - Elmarakby, Ahmed A
AU  - Elmarakby AA
AD  - Department of Oral Biology, Georgia Regents University, Augusta, GA, USA; 
      Department of Pharmacology & Toxicology, Georgia Regents University, Augusta, GA, 
      USA.
LA  - eng
GR  - R01 EY023315/EY/NEI NIH HHS/United States
PT  - Journal Article
DEP - 20150530
PL  - United States
TA  - J Diabetes Metab
JT  - Journal of diabetes & metabolism
JID - 101549907
PMC - PMC4727755
MID - NIHMS730919
OTO - NOTNLM
OT  - 12/15-LO Deficient mice
OT  - Baicalein
OT  - Diabetes
OT  - Inflammation
OT  - Kidney
OT  - Oxidative stress
OT  - Proteinuria
EDAT- 2016/01/30 06:00
MHDA- 2016/01/30 06:01
PMCR- 2016/01/26
CRDT- 2016/01/30 06:00
PHST- 2016/01/30 06:00 [entrez]
PHST- 2016/01/30 06:00 [pubmed]
PHST- 2016/01/30 06:01 [medline]
PHST- 2016/01/26 00:00 [pmc-release]
AID - 555 [pii]
AID - 10.4172/2155-6156.1000555 [doi]
PST - ppublish
SO  - J Diabetes Metab. 2015 Jun;6(6):555. doi: 10.4172/2155-6156.1000555. Epub 2015 
      May 30.