PMID- 28289922
OWN - NLM
STAT- MEDLINE
DCOM- 20180308
LR  - 20181113
IS  - 1568-5608 (Electronic)
IS  - 0925-4692 (Linking)
VI  - 25
IP  - 3
DP  - 2017 Jun
TI  - Curcumin inhibits lipopolysaccharide (LPS)-induced endotoxemia and airway 
      inflammation through modulation of sequential release of inflammatory mediators 
      (TNF-alpha and TGF-beta1) in murine model.
PG  - 329-341
LID - 10.1007/s10787-017-0334-3 [doi]
AB  - OBJECTIVE: Curcumin (diferuloylmethane), a major component of turmeric is well 
      known for its anti-inflammatory potential. Present study investigates sequential 
      release of inflammatory mediators post LPS challenge (10 mg/kg,i.p.) causing lung 
      inflammation and its modulation by curcumin through different routes (20 mg/kg, 
      i.p and 10 mg/kg, i.n.) in murine model. Dexamethasone (1 mg/kg, i.p) was used as 
      standard drug. METHODS: Lung Inflammation was evaluated by histopathological 
      analysis, myeloperoxidase (MPO) activity followed by inflammatory cell count and 
      total protein content measurements in bronchoalveolar fluid (BALF). Reactive 
      oxygen species (ROS), nitrite and TNF-alpha levels were measured as markers of 
      endotoxin shock at different time points (1-72 h). The mRNA expression of 
      transforming growth factors-beta1 (TGF-beta1), iNOS and Toll-like receptor-4 (TLR-4) 
      were measured followed by Masson's trichrome staining and hydroxyproline levels 
      as collagen deposition marker leading to fibrotic changes in lungs. RESULTS: We 
      found that LPS-induced lung inflammation and injury was maximum 24-h post LPS 
      challenge shown by MPO and histological analysis which was further supported by 
      elevated nitrite and ROS levels whereas TNF-alpha level was highest after 1 h. 
      Endotoxin-induced mortality was significantly reduced in curcumin (i.p) 
      pretreatment groups up to 72-h post LPS challenge. Significant inhibition in mRNA 
      expression of iNOS, TGF-beta1 and TNF-alpha level was noted after curcumin treatment 
      along with lowered MPO activity, inflammatory cell count, ROS, nitrite levels and 
      collagen deposition in lungs. CONCLUSION: Our results suggest that higher 
      endotoxin dose causes inflammatory mediator release in chronological order which 
      tend to increase with time and reached maximum after 24-h post-endotoxin (LPS) 
      exposure. Intraperitoneal route of curcumin administration was better in 
      modulating inflammatory mediator release in early phase as compared to intranasal 
      route of administration. It can be used as supplementary therapeutic intervention 
      at early stage of endotoxemia, having fewer side effects.
FAU - Kumari, Asha
AU  - Kumari A
AD  - Department of Zoology, MMV, Banaras Hindu University, Varanasi, 221005, India.
FAU - Dash, D
AU  - Dash D
AD  - Department of Biochemistry, Institute of Medical Sciences, Banaras Hindu 
      University, Varanasi, 221005, India.
FAU - Singh, Rashmi
AU  - Singh R
AD  - Department of Zoology, MMV, Banaras Hindu University, Varanasi, 221005, India. 
      rashmirs98@rediffmail.com.
LA  - eng
PT  - Journal Article
DEP - 20170313
PL  - Switzerland
TA  - Inflammopharmacology
JT  - Inflammopharmacology
JID - 9112626
RN  - 0 (Inflammation Mediators)
RN  - 0 (Lipopolysaccharides)
RN  - 0 (RNA, Messenger)
RN  - 0 (Reactive Oxygen Species)
RN  - 0 (Toll-Like Receptor 4)
RN  - 0 (Transforming Growth Factor beta1)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - EC 1.11.1.7 (Peroxidase)
RN  - EC 1.14.13.39 (Nitric Oxide Synthase Type II)
RN  - IT942ZTH98 (Curcumin)
SB  - IM
MH  - Animals
MH  - Bronchoalveolar Lavage Fluid/cytology
MH  - Curcumin/*pharmacology
MH  - Disease Models, Animal
MH  - Endotoxemia/chemically induced/*drug therapy/metabolism
MH  - Inflammation Mediators/*metabolism
MH  - Lipopolysaccharides/pharmacology
MH  - Lung/drug effects/metabolism
MH  - Mice
MH  - Nitric Oxide Synthase Type II/metabolism
MH  - Peroxidase/metabolism
MH  - Pneumonia/chemically induced/*drug therapy/metabolism
MH  - RNA, Messenger/metabolism
MH  - Reactive Oxygen Species/metabolism
MH  - Toll-Like Receptor 4/metabolism
MH  - Transforming Growth Factor beta1/*metabolism
MH  - Tumor Necrosis Factor-alpha/*metabolism
OTO - NOTNLM
OT  - Endotoxemia
OT  - Fibrosis
OT  - Inflammation
OT  - Mortality
EDAT- 2017/03/16 06:00
MHDA- 2018/03/09 06:00
CRDT- 2017/03/15 06:00
PHST- 2016/11/10 00:00 [received]
PHST- 2017/02/23 00:00 [accepted]
PHST- 2017/03/16 06:00 [pubmed]
PHST- 2018/03/09 06:00 [medline]
PHST- 2017/03/15 06:00 [entrez]
AID - 10.1007/s10787-017-0334-3 [pii]
AID - 10.1007/s10787-017-0334-3 [doi]
PST - ppublish
SO  - Inflammopharmacology. 2017 Jun;25(3):329-341. doi: 10.1007/s10787-017-0334-3. 
      Epub 2017 Mar 13.