Gene/Protein Disease Symptom Drug Enzyme Compound
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In the rat, as in most other polytocous species, fetuses tend to be relatively evenly spaced along the uterine horn, perhaps to minimize possible effects of local overcrowding on placental function and fetal growth. Here we administered 2 mg of indomethacin, in split doses on day 5 of gestation, in an attempt to disturb evenness of spacing and so reveal local overcrowding effects, if any. The effects on spacing, expressed as the coefficient of deviation of distances between neighboring implants (CVd%) and correlations between fetal and placental weights and distance to neighbors, was examined on day 16 and day 22 of gestation to cover the period of rapid fetal growth. Indomethacin markedly affected evenness of spacing; at day 16, CVd% increased from a control value of 19.2 to 50.8% and at day 22 from 27.5 to 41.2%. Despite the increased variability of spacing and consequent local crowding, including examples of conjoined placentas in the treated rats, there was no evidence that these local factors affected placental growth or weight of individual fetuses. Indomethacin, however, had a general effect on placental and fetal growth. At day 16, mean fetal weights were retarded but by day 22 had caught up to those of control litters, and this was accompanied by significant placental hypertrophy. Collectively, these results show that the uterus has sufficient reserve to cope with relatively uneven spacing of fetuses and have provided a model for examining catch-up growth of fetuses and accompanying placental changes.
Anat Rec 1989 Oct
PMID:Effects of indomethacin on spacing of conceptuses within the uterine horn and on fetal and placental growth in the rat. 281 23

The mutagenicity of 6 marketed non-steroidal anti-inflammatory drugs (aspirin, flufenamic acid, diclofenac sodium, indomethacin, naproxen and chloroquine) as well as 2 new anti-inflammatory drugs (tenoxicam and carprofen) was examined by using in vitro bacterial systems (repair test and reversion test). None of them was mutagenic on Ames' reversion test. However, they differed in their responses to repair tests. Tenoxicam, carprofen, aspirin, flufenamic acid and naproxen were not mutagenic in either rec- or pol-assays, whereas chloroquine only showed positive results in the pol-assay system. Indomethacin and diclofenac sodium exhibited a slightly stronger inhibitory activity against B. subtilis rec- mutant than against its rec+ counterpart in rec-assay, which was much weaker than AF-2. Thus their mutagenicity was questionable. These results confirm the usefulness of DNA-repair assays as a complementary endpoint to gene mutation in assessing the genotoxic potential of environmental compounds.
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PMID:Mutagenicity examination of several non-steroidal anti-inflammatory drugs in bacterial systems. 644 12

The effects of the prostaglandin synthesis inhibitor, indomethacin, on the preovulatory morphology of apical follicle walls have been examined by transmission electron microscopy. Immature mice, superovulated with 5 IU pregnant mare serum (PMS) followed 40 hours later by 80 IU luteinizing hormone (LH) were treated with either 10 mg/kg indomethacin or an equivalent volume of the indomethacin vehicle 10 minutes prior to LH. Follicular apices from both groups were compared at 12 hours post-LH. Indomethacin treatment suppressed many of the morphological changes normally occurring in the apex during preovulatory development. Whereas apices from vehicle-treated animals demonstrated marked deterioration, dissociation, and thinning of tissue, the cell layers of apices from indomethacin-treated animals remained thickened and tightly packed, with limited signs of disruption. The results presented herein are consistent with the idea that prostaglandins are essential mediators of ovulation and suggest that these lipids augment apical rupture by mobilizing granulosa cells and stimulating the loss of connective tissue elements.
Anat Rec 1983 Feb
PMID:An ultrastructural study of preovulatory apical development in mouse ovarian follicles: effects of indomethacin. 684 67

Prostaglandin F2 alpha (PGF2 alpha) is capable of inducing a decidual cell reaction (DCR) in the hormonally prepared rat. In the present work indomethacin, a PG synthetase inhibitor, was used to determine whether PGF2 alpha is involved in the DCR induced by artificial stimulation of the endometrium. Thirty-seven animals were oophorectomized and subsequently given daily injections of progesterone for 6 days and one injection of estradiol 17 beta on the fourth day. Later on the fourth day, one of several experimental maneuvers was carried out on the right uterine horn of each animal; these included: 1) introduction of phosphate-buffered saline (PBS) twice into the uterus, 2) intrauterine injection of PGF2 alpha with no subsequent application or manipulation, 3) intrauterine injection of indomethacin followed by subsequent injection of PGF2 alpha, 4) intrauterine injection of indomethacin with subsequent artificial stimulation (scratch), 5) intrauterine injection of PBS with subsequent scratch, 6) scratch followed by injection of PBS, and 7) scratch followed by a second scratch. The extent of the ensuing DCR was assessed 48 h later by measurement of horn weight, by light and electron microscopy, by ranking the DCR, and by the mitotic index. Indomethacin significantly reduced the horn weight in animals treated with scratch but had a much less marked effect on animals treated with PGF2 alpha. Similarly the rank of the DCR and the mitotic index were significantly less in endometria treated by indomethacin with scratch than those treated by indomethacin with PGF2 alpha. From these findings it was concluded that the DCR induced by scratch was inhibited, but not abolished, when preceded by indomethacin. Conversely the DCR induced by PGF2 alpha was not inhibited by indomethacin, thus demonstrating that when local generation of PG is reduced or abolished, PGF2 alpha can sustain the decidual cell response.
Anat Rec 1982 Nov
PMID:Inhibition of artificially induced decidual cell reaction by indomethacin in the mature oophorectomized rat. 696 26

Tooth drift requires the deformation of the root socket and the adjustment of the other components of the attachment apparatus, namely, the periodontal ligament (PDL) and the cementum. Indomethacin (7.5 mg/kg/d), an inhibitor of prostanoid synthesis, provoked in rats a depression in the bone resorption effecting the deformation of the socket (Lasfargues and Saffar, Anat. Rec., 234:310-316, 1992). In the present paper we examined the consequence of this treatment both on the PDL and the root surface. After 3 days of treatment, when osteoclastic resorption was not yet disturbed, the root had been markedly resorbed (P < 0.05) opposite the resorbing bone surface; at that time the PDL width remained in the normal range. After 7 days, i.e., when the bone resorption was depressed, the PDL was widened as the result of the ongoing root resorption. Despite the extensive root resorption, the anchorage of the PDL fibers appeared to remain effective, suggesting that it was rapidly restored. On day 14 at the time of the bone resorption recovery, cementum was deposited in the root resorption lacunae and the PDL width had returned to its control value. As early as day 3 the daily rate of dentine formation increased in the pulp area subjacent to the root resorption lacunae (P < 0.01). These data demonstrate that i) the responses of the different components of the periodontal apparatus are coordinated to allow for the maintainance of the PDL width so that when bone resorption is disturbed, root resorption compensates for it, and ii) the odontoclasts can differentiate and resorb under prostanoid inhibition whilst osteoclastic resorption of the bone socket is inhibited.
Anat Rec 1993 Dec
PMID:Inhibition of prostanoid synthesis depresses alveolar bone resorption but enhances root resorption in the rat. 831 Dec 58