Retinoic acid hydroxylation and teratogenesis in lake sturgeon (Acipenser fulvescens) from the St. Lawrence River and Abitibi region, Quebec

1999 ◽  
Vol 56 (8) ◽  
pp. 1428-1436 ◽  
Author(s):  
Christian Doyon ◽  
Réjean Fortin ◽  
Philip A Spear

All-trans-retinoic acid (RA) is an extremely active form of vitamin A; however, excessive or insufficient concentrations elicit anomalies including those associated with limb and craniofacial development. Lake sturgeon (Acipenser fulvescens) from the St. Lawrence River and tributaries were estimated to have a 2.9% incidence of fin and craniofacial malformations. Among larvae raised in artificial streams, a greater incidence of fin malformations (6.3%; p < 0.001) occurred in St. Lawrence River sturgeon compared with larvae from the Abitibi region. To test the hypothesis that the differences in rate of malformations may be associated with metabolic imbalances of RA, cytochrome P-450 dependent conversion to 4-hydroxyretinoic acid (4-OH-RA) was investigated. Optimal assay conditions are described for in vitro 4-OH-RA production in liver microsomes. Enzyme activity tended to decrease with increasing age and gonadal development in fish collected from Abitibi, but no statistically significant effects of sex, age, length, or gonadal development were discerned. The rate of 4-OH-RA formation was 3.5-fold greater (p < 0.0001) in the St. Lawrence sturgeon while the concentrations of cytochrome P-450 inducing PCBs (expressed as dioxin toxic equivalents) were 20-fold greater in a composite liver sample of the St. Lawrence sturgeon. Liver retinoid concentrations were negatively correlated (p < 0.0001) with RA hydroxylation rate. These results are consistent with the possibility that cytochrome P-450 dependent RA metabolism increased by chemical contaminants is associated with developmental anomalies in the St. Lawrence sturgeon.

2001 ◽  
Vol 79 (8) ◽  
pp. 1472-1489 ◽  
Author(s):  
Julie D'Amours ◽  
Stéphanie Thibodeau ◽  
Réjean Fortin

Several fish species that spawn in lotic habitats have a larval-drift phase which is a major determinant of their reproductive success. The main objective of this study was to compare seasonal, diel, longitudinal, transverse, and vertical variations in rates of lake sturgeon (Acipenser fulvescens), Stizostedion spp., Catostomus spp., Moxostoma spp., quillback (Carpiodes cyprinus), and mooneye (Hiodon tergisus) larval drift in Des Prairies River (DPR) near Montreal (Quebec), which is one of the major lotic spawning habitats of the St. Lawrence River system. Larval sampling was conducted in the spring of 1994 and 1995 for the six taxa, and on a more restricted basis for lake sturgeon in 1996–1998, using drift nets set at several transects, stations, depths, and periods of the day, along a 19 km long section of river beginning ca. 2 km downstream from the DPR power house. For all taxa except lake sturgeon, peak larval drift occurred ca. 1 week earlier in 1995 than in 1994. The sequence was very similar between years, beginning with Stizostedion spp., followed by Catostomus spp., then lake sturgeon, quillback, and mooneye drifting simultaneously, and finally Moxostoma spp. Generally, for all taxa except quillback, whose multimodal drift pattern suggests intermittent, prolonged spawning, larval-drift profiles showed one major seasonal mode, which was observed simultaneously at all transects. For all taxa except quillback, drift rates peaked between 21:00 and 03:00 and were minimal during daylight hours. Lake sturgeon and Stizostedion spp. larval drift rates decreased radically from the most upstream to the most downstream transect, suggesting that both taxa spawn mostly in the vicinity of the DPR power house. More studies are required to explain this longitudinal decline in drift rates, particularly for lake sturgeon. The other taxa showed longitudinal variation in larval drift rates, suggesting that they spawn near the DPR power house and (or) in the Île de Pierre Rapids, ca. 12 km downstream. At all transects, larval drift rates for the six taxa were generally higher in the right half (Montreal) of the river, suggesting that eggs are deposited mostly in this part of the river at the two major spawning areas and that larvae tend to remain in the same general corridors during downstream migration. For all taxa, though to a lesser extent for lake sturgeon, nocturnal drift rates tend to be higher near the surface than at mid-depth and near the bottom, the reverse situation being observed for diurnal drift rates.


2012 ◽  
Vol 42 (1) ◽  
pp. 19-26 ◽  
Author(s):  
Louis DiVincenti ◽  
Jeff Wyatt ◽  
Heather Priest ◽  
Dawn Dittman ◽  
Rodger Klindt ◽  
...  

Pharmaceutics ◽  
2020 ◽  
Vol 12 (11) ◽  
pp. 1129
Author(s):  
Trang Nguyen Kieu Doan ◽  
Dang-Khoa Vo ◽  
Hyojung Kim ◽  
Anusha Balla ◽  
Yunjong Lee ◽  
...  

The compound 1α,25-Dihydroxyvitamin D3 (1,25(OH)2D3) is the active form of vitamin D3 and a representative ligand of the vitamin D receptor (VDR). Previous studies have described the impacts of 1,25(OH)2D3 on a small number of cytochrome P450 (CYP) and uridine diphosphate-glucuronyltransferase (UGT) enzymes, but comparatively little is known about interactions between several important CYP and UGT isoforms and 1,25(OH)2D3 in vitro and/or in vivo. Thus, we investigated the effects of 1,25(OH)2D3 on the gene and protein expressions and functional activities of selected CYPs and UGTs and their impacts on drug pharmacokinetics in rats. The mRNA/protein expressions of Cyp2b1 and Cyp2c11 were downregulated in rat liver by 1,25(OH)2D3. Consistently, the in vitro metabolic kinetics (Vmax and CLint) of BUP (bupropion; a Cyp2b1 substrate) and TOL (tolbutamide; a Cyp2c11 substrate) were significantly changed by 1,25(OH)2D3 treatment in liver microsomes, but the kinetics of acetaminophen (an Ugt1a6/1a7/1a8 substrate) remained unaffected, consistent with Western blotting data for Ugt1a6. In rat pharmacokinetic studies, the total body clearance (CL) and nonrenal clearance (CLNR) of BUP were significantly reduced by 1,25(OH)2D3, but unexpectedly, the total area under the plasma concentration versus time curve from time zero to infinity (AUC) of hydroxybupropion (HBUP) was increased probably due to a marked reduction in the renal clearance (CLR) of HBUP. Additionally, the AUC, CL, and CLNR for TOL and the AUC for 4-hydroxytolbutamide (HTOL) were unaffected by 1,25(OH)2D3 in vivo. Discrepancies between observed in vitro metabolic activity and in vivo pharmacokinetics of TOL were possibly due to a greater apparent distribution volume at the steady-state (Vss) and lower plasma protein binding in 1,25(OH)2D3-treated rats. Our results suggest possible drug-drug and drug-nutrient interactions and provide additional information concerning safe drug combinations and dosing regimens for patients taking VDR ligand drugs including 1,25(OH)2D3.


Molecules ◽  
2020 ◽  
Vol 25 (3) ◽  
pp. 546 ◽  
Author(s):  
Shuichi Setoguchi ◽  
Ryoji Hidaka ◽  
Nami Nagata-Akaho ◽  
Daisuke Watase ◽  
Mitsuhisa Koga ◽  
...  

The aim of this study was to develop a prodrug of ubiquinol-10 (UqH-10), the active form of ubiquinone-10 (Uq-10), for oral delivery. Bioavailability of UqH-10 is hampered by its high susceptibility to oxidation and water-insolubility. We prepared three novel N,N-dimethylglycine ester derivatives of UqH-10, including a 1-monoester (UqH-1-DMG), 4-monoester (UqH-4-DMG), and 1,4-bis-ester (UqH-DMG), and assessed their physicochemical properties in vitro and in vivo. UqH-DMG spontaneously formed an aqueous micelle solution comprising 20 nm particles at 36.5 °C. Cationic UqH-DMG formed nano-sized (5 nm) mixed-micelles with taurocholic acid. Reconversion of the derivatives to UqH-10 was accelerated in human liver microsomes. The oral bioavailability of UqH-10 after administration of UqH-derivatives or Uq-10 was determined in fasted and postprandial rats secreting normal and high levels of bile, respectively. In fasted rats, plasma UqH-10 after UqH-derivatives administration reached Cmax at 2–3 h and after Uq-10 administration, it remained low. The AUC0-24h of UqH-10 after UqH-derivatives administration was 2–3-fold higher than that after Uq-10 administration. In postprandial rats, the Tmax of UqH-10 after UqH-derivatives administration was an hour earlier than after Uq-10 administration. In conclusion, cationic UqH-derivatives are convenient prodrugs that enhance UqH-10 bioavailability by forming nanosized mixed-micelles with intestinal bile acids.


1992 ◽  
Vol 49 (7) ◽  
pp. 1336-1342 ◽  
Author(s):  
Sylvie Guénette ◽  
Daniel Goyette ◽  
Réjean Fortin ◽  
Jean Leclerc ◽  
Nelson Fournier ◽  
...  

Measurements of annual increments on cross-sections of the first ray of the pectoral fin of 125 St. Lawrence River female lake sturgeon (Acipenser fulvescens) aged 24 yr and older were used to test the correspondance between growth patterns at the margin of the sections and the state of maturity of the fish. For each of the 21 females aged 34 yr and older, and for the upper Ottawa River specimens presented by Roussow (1957. J. Fish. Res. Board Can. 14: 553–572), annual increments were treated as a temporal series and analysed with the contingency periodogram. The mean age at first spawning was determined using the age at the end of the first belt of crowded annuli, following Roussow. Only 3 of the 21 females aged 34 yr and older showed a typical succession of belts of large and narrow annuli. The most frequent periods were 5–11 yr, using the periodogram, as compared with 6–9 yr for Roussow' specimens. No significant correspondance was found between the pattern of the last five annual increments and the state of maturity. The mean age at first spawning, estimated at 19 yr by this technique, is lower than the mean age of sexual maturity determined for St. Lawrence River females based on the examination of the gonads (26 yr).


1981 ◽  
Vol 90 (1) ◽  
pp. 103-112 ◽  
Author(s):  
TIIU HANSSON ◽  
JAN-ÅKE GUSTAFSSON

The metabolism of 4-androstene-3,17-dione by liver microsomes from juvenile rainbow trout, Salmo gairdnerii, was studied in vitro. Hypophysectomy of the fish significantly increased mean hepatic 17-hydroxysteroid oxidoreductase activity when compared with that from sham-operated fish but none of the other enzyme activities investigated were affected. Administration of oestradiol-17β resulted in a significant decrease in mean hepatic 6β-hydroxylase activity and total cytochrome P-450 content but had no effect on the 16-hydroxylation or on the reductive metabolism of androstenedione. The effect of oestradiol-17β on hepatic 6β-hydroxylase activity was as pronounced after hypophysectomy as after sham-operation indicating that these effects of oestradiol-17β are mainly direct and independent of the pituitary gland. The results indicate that hypophysial hormone(s) as well as oestradiol-17β play a role in the regulation of hepatic steroid metabolism in trout.


1995 ◽  
Vol 52 (3) ◽  
pp. 512-520 ◽  
Author(s):  
Aristocle Ndayibagira ◽  
Marie-Josée Cloutier ◽  
Perry D. Anderson ◽  
Philip A. Spear

A single i.p. injection of 5 μg 3,3′,4,4′-tetrachlorobiphenyl (TCBP)/g body mass in adult brook trout (Salvelinus fontinalis) resulted in decreased (p < 0.0001) growth rate despite pair feeding. Plasma retinol decreased (p < 0.0037). Intestinal retinyl palmitate (RP) and 3,4-dehydroretinyl palmitate (DRP) concentrations decreased in TCBP-injected males (RP, p < 0.0143; DRP, p < 0.0009), whereas retinoid levels did not decrease significantly in TCBP-injected females. The RP:DRP ratio in trout liver increased (p < 0.0001). These results suggested that DRP is more sensitive than RP to the effects of TCBP. No significant differences in ovarian retinoids occurred in post-spawning trout. Field validation of the effects on intestinal retinoids was conducted with lake sturgeon (Acipenser fulvescens) caught at a contaminated site on the Des Prairies River near Montréal (St. Lawrence River population) and reference sturgeon taken from a site near the origin of the Ottawa River in LaVerendrye Park. Intestinal retinoid concentrations were lower (RP, p < 0.0008; DRP, p < 0.0004) in the St. Lawrence River sturgeon. Our results demonstrate that a coplanar PCB is capable of altering vitamin A dynamics in several tissues and organs, and may cause a lowering of retinoids in the intestine.


Sign in / Sign up

Export Citation Format

Share Document