PMID- 16607633
OWN - NLM
STAT- MEDLINE
DCOM- 20060609
LR  - 20121115
IS  - 1542-9733 (Print)
IS  - 1542-9733 (Linking)
VI  - 77
IP  - 2
DP  - 2006 Apr
TI  - Inhibiting matrix metalloproteinases with prinomastat produces abnormalities in 
      fetal growth and development in rats.
PG  - 95-103
AB  - BACKGROUND: Matrix metalloproteinases (MMPs) play key roles in remodeling of the 
      extracellular matrix during embryogenesis and fetal development. The objective of 
      this study was to determine the effects of prinomastat, a potent selective MMP 
      inhibitor, on fetal growth and development. METHODS: Prinomastat (25, 100, 250 
      mg/kg/day, p.o.) was administered to pregnant female Sprague-Dawley rats on 
      gestational days (GD) 6-17. A Cesarian section was carried out on GD 20 and the 
      fetuses were evaluated for viability and skeletal and soft tissue abnormalities. 
      RESULTS: Prinomastat treatment at the 250 mg/kg/day dose produced a decrease in 
      body weight and food consumption in the dams. A dose-dependent increase in 
      post-implantation loss was observed in the 100 and 250 mg/kg/day-dose groups, 
      resulting in only 22% of the dams having viable litters for evaluation at the 250 
      mg/kg/day dose. Fetal skeletal tissue variations and malformations were present 
      in all prinomastat treated groups and their frequency increased with dose. 
      Variations and malformation in fetal soft tissue were also increased at the 100 
      and 250 mg/kg/day doses. Prinomastat also interfered with fetal growth of rat 
      embryo cultures in vitro. CONCLUSIONS: These data confirm that MMP inhibition has 
      a profound effect on fetal growth and development in vivo and in vitro.
CI  - Birth Defects Research (Part B) 77:95-103, 2006. (c) 2006 Wiley-Liss, Inc.
FAU - Younis, Husam S
AU  - Younis HS
AD  - Worldwide Safety Sciences, Pfizer Global Research and Development, La Jolla 
      Laboratories, San Diego, California 92121, USA. husam.younis@pfizer.com
FAU - Jessen, Bart A
AU  - Jessen BA
FAU - Wu, Ellen Y
AU  - Wu EY
FAU - Stevens, Gregory J
AU  - Stevens GJ
LA  - eng
PT  - Journal Article
PL  - United States
TA  - Birth Defects Res B Dev Reprod Toxicol
JT  - Birth defects research. Part B, Developmental and reproductive toxicology
JID - 101155115
RN  - 0 (Enzyme Inhibitors)
RN  - 0 (Matrix Metalloproteinase Inhibitors)
RN  - 0 (Organic Chemicals)
RN  - 10T6626FRK (prinomastat)
SB  - IM
MH  - Animals
MH  - Body Weight/drug effects
MH  - Bone and Bones/abnormalities
MH  - Eating/drug effects
MH  - Embryo Culture Techniques
MH  - Embryo Loss/chemically induced
MH  - Embryo, Mammalian/abnormalities/drug effects
MH  - Enzyme Inhibitors/pharmacokinetics/*toxicity
MH  - Female
MH  - Fetus/*abnormalities/drug effects/enzymology
MH  - *Matrix Metalloproteinase Inhibitors
MH  - Organ Size/drug effects
MH  - Organic Chemicals/pharmacokinetics/*toxicity
MH  - Pregnancy
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Uterus/anatomy & histology/drug effects
EDAT- 2006/04/12 09:00
MHDA- 2006/06/10 09:00
CRDT- 2006/04/12 09:00
PHST- 2006/04/12 09:00 [pubmed]
PHST- 2006/06/10 09:00 [medline]
PHST- 2006/04/12 09:00 [entrez]
AID - 10.1002/bdrb.20073 [doi]
PST - ppublish
SO  - Birth Defects Res B Dev Reprod Toxicol. 2006 Apr;77(2):95-103. doi: 
      10.1002/bdrb.20073.