PMID- 17934920
OWN - NLM
STAT- MEDLINE
DCOM- 20080107
LR  - 20191110
IS  - 0148-0545 (Print)
IS  - 0148-0545 (Linking)
VI  - 30
IP  - 4
DP  - 2007
TI  - Chemopreventive effects of nonsteroidal anti-inflammatory drugs in the membrane 
      lipid composition and fluidity parameters of the 1,2-dimethylhydrazine-induced 
      colon carcinogenesis in rats.
PG  - 293-309
AB  - Nonsteroidal anti-inflammatory drugs (NSAIDs) such as aspirin, celecoxib, and 
      etoricoxib are reported to act as chemopreventive agents in experimental colon 
      cancer induced by 1,2-dimethylhydrazine (DMH) as they are known cyclooxygenase 
      (COX) enzyme inhibitors. To determine whether NSAIDs can also effectively 
      modulate the membrane lipid compositions and the fluidity parameters of colonic 
      brush border membrane, rats were injected subcutaneously (s.c.) with DMH 30 mg/kg 
      body weight per week for 6 weeks. The animals were simultaneously treated with 
      NSAIDs orally at the dose of aspirin, 60 mg/kg body weight; celecoxib, 6 mg/kg 
      body weight; and etoricoxib, 0.6 mg/kg body weight. The animals were sacrificed 
      after 6 weeks of treatments. Brush border membrane was isolated from proximal and 
      distal portions of the colon. Membrane lipids were extracted and analyzed while 
      the fluidity parameters were assessed by steady-state fluorescence polarization 
      technique using the membrane extrinsic fluorophore 1,6-diphenyl-1,3,5-hexatriene 
      (DPH). The translational diffusion was measured by using the excimer formation of 
      pyrene incorporated in the membrane. Colonic mucosal changes in DMH alone and 
      DMH+NSAID treated animals were assessed histologically. The results demonstrate 
      that (a) there is a distinct occurrence of premalignant alterations in 
      DMH-induced colon in the form of multiple plaque lesions (MPLs), which were 
      greatly reduced by the NSAIDs used, (b) the membrane lipid changes in DMH-induced 
      colon were completely restored back, (c) the alterations in membrane fluorescence 
      polarization and the fluidity parameters are partially recovered, particularly 
      with etoricoxib, and (d) the pyrene excimer formation process was completely 
      restored. It may be concluded that the NSAIDs, particularly the coxib group of 
      the drugs (COX-2 selective), are effective in chemoprevention in the DMH-induced 
      colon carcinogenesis and membrane alterations.
FAU - Kanwar, Shailender Singh
AU  - Kanwar SS
AD  - Department of Biophysics, Panjab University, Chandigarh, India.
FAU - Vaiphei, Kim
AU  - Vaiphei K
FAU - Nehru, Bimla
AU  - Nehru B
FAU - Sanyal, Sankar N
AU  - Sanyal SN
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Drug Chem Toxicol
JT  - Drug and chemical toxicology
JID - 7801723
RN  - 0 (Anti-Inflammatory Agents, Non-Steroidal)
RN  - 0 (Anticarcinogenic Agents)
RN  - 0 (Carcinogens)
RN  - 0 (Membrane Lipids)
RN  - IX068S9745 (1,2-Dimethylhydrazine)
SB  - IM
MH  - 1,2-Dimethylhydrazine
MH  - Animals
MH  - Anti-Inflammatory Agents, Non-Steroidal/administration & 
      dosage/pharmacology/*therapeutic use
MH  - Anticarcinogenic Agents/administration & dosage/pharmacology/*therapeutic use
MH  - Body Weight/drug effects
MH  - Carcinogens
MH  - Colon/drug effects/metabolism/ultrastructure
MH  - Colonic Neoplasms/chemically induced/metabolism/*prevention & control
MH  - Male
MH  - Membrane Fluidity/*drug effects
MH  - Membrane Lipids/*metabolism
MH  - Microvilli/drug effects/metabolism
MH  - Rats
MH  - Rats, Sprague-Dawley
EDAT- 2007/10/16 09:00
MHDA- 2008/01/08 09:00
CRDT- 2007/10/16 09:00
PHST- 2007/10/16 09:00 [pubmed]
PHST- 2008/01/08 09:00 [medline]
PHST- 2007/10/16 09:00 [entrez]
AID - 782954884 [pii]
AID - 10.1080/01480540701522106 [doi]
PST - ppublish
SO  - Drug Chem Toxicol. 2007;30(4):293-309. doi: 10.1080/01480540701522106.