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Environmental Science and Pollution... Nov 2020The toxicity of endocrinologically active pharmaceuticals finasteride (FIN) and melengestrol acetate (MGA) was assessed in freshwater mussels, including acute (48 h)...
The toxicity of endocrinologically active pharmaceuticals finasteride (FIN) and melengestrol acetate (MGA) was assessed in freshwater mussels, including acute (48 h) aqueous tests with glochidia from Lampsilis siliquoidea, sub-chronic (14 days) sediment tests with gravid female Lampsilis fasciola, and chronic (28 days) sediment tests with juvenile L. siliquoidea, and in chronic (42 days) sediment tests with the amphipod Hyalella azteca and the mayfly Hexagenia spp. Finasteride was not toxic in acute aqueous tests with L. siliquoidea glochidia (up to 23 mg/L), whereas significant toxicity to survival and burial ability was detected in chronic sediment tests with juvenile L. siliquoidea (chronic value (ChV, the geometric mean of LOEC and NOEC) = 58 mg/kg (1 mg/L)). Amphipods (survival, growth, reproduction, and sex ratio) and mayflies (growth) were similarly sensitive (ChV = 58 mg/kg (1 mg/L)). Melengestrol acetate was acutely toxic to L. siliquoidea glochidia at 4 mg/L in aqueous tests; in sediment tests, mayflies were the most sensitive species, with significant growth effects observed at 37 mg/kg (0.25 mg/L) (ChV = 21 mg/kg (0.1 mg/L)). Exposure to sublethal concentrations of FIN and MGA had no effect on the (luring and filtering) behaviour of gravid L. fasciola, or the viability of their brooding glochidia. Based on the limited number of measured environmental concentrations of both chemicals, and their projected concentrations, no direct effects are expected by these compounds individually on the invertebrates tested. However, organisms are exposed to contaminant mixtures in the aquatic environment, and thus, the effects of FIN and MGA as components of these mixtures require further investigation.
Topics: Animals; Bivalvia; Ephemeroptera; Female; Finasteride; Invertebrates; Melengestrol Acetate; Pharmaceutical Preparations; Water Pollutants, Chemical
PubMed: 32696412
DOI: 10.1007/s11356-020-10121-7 -
Journal of Environmental Sciences... May 2023Altrenogest (ALT), drospirenone (DRO), and melengestrol acetate (MLA) are three highly potent synthetic progestins that can be released into agricultural soils, while...
Altrenogest (ALT), drospirenone (DRO), and melengestrol acetate (MLA) are three highly potent synthetic progestins that can be released into agricultural soils, while their fate in soil minerals remains unclear. This study explored the transformation of these progestins in MnO, SiO, and ferrihydrite suspensions and identified their transformation products (TPs) via high resolution mass spectrometry and density functional theory calculations. Transformations were only observed for DRO and MLA in SiO suspension and ALT in MnO suspension (half-lives = 0.86 min - 9.90 day). ALT transformation was facilitated at higher MnO loadings, while DRO and MLA transformations were inhibited at higher SiO loadings. These data indicated that hydrophobic partitioning interaction was dominant at higher SiO loadings rather than specific interaction, which limited subsequent surface-catalyzed transformation. ALT transformation rate decreased with increasing pH because MnO reduction requires proton participation. In contrast, relatively high pH facilitated MLA and DRO transformation, indicating that base-catalyzed hydrolysis occurred in SiO suspension. The clustermap demonstrated the formation of abundant TPs. Lactone ring and acetoxy group hydrolysis was the major transformation pathway for DRO and MLA, with estimated yields of 57.7% and 173.2% at 6 day, respectively. ALT experienced C12 hydroxylation and formed the major TP 326g (yield of 15.4% at 8 hr). ALT also experienced allyl group oxidation and subsequent C5 hydroxylation, forming the major TP 344a (yield of 14.1% at 8 hr). This study demonstrates that TPs of metastable progestins are likely the main species in soils and that TP identification is a particular priority for risk assessment.
Topics: Soil; Manganese Compounds; Progestins; Suspensions; Silicon Dioxide; Oxides; Minerals; Progesterone Congeners; Oxidation-Reduction
PubMed: 36522069
DOI: 10.1016/j.jes.2022.06.007 -
Environmental Science and Pollution... Jan 2021
PubMed: 33216304
DOI: 10.1007/s11356-020-11617-y -
Bioorganic Chemistry Nov 2020Glomerella fusaroide, and Rhizopus stolonifer were effectively able to transform the steroidal hormone melengestrol acetate (MGA) (1) into four (4) new metabolites,...
Glomerella fusaroide, and Rhizopus stolonifer were effectively able to transform the steroidal hormone melengestrol acetate (MGA) (1) into four (4) new metabolites, 17α-acetoxy-11α-hydroxy-6-methyl-16-methylenepregna-4,6-diene-3,20-dione (2), 17α-acetoxy-11α-hydroxy-6-methyl-16-methylenepregna-1,4,6-triene-3,20-dione (3), 17α-acetoxy-6,7α-epoxy-6β-methyl-16-methylenepregna-4,6-diene-3,20-dione (4), and 17α-acetoxy-11β,15β-dihydroxy-6-methyl-16-methylenepregna-4,6-diene-3,20-dione (5). All these compounds were structurally characterized by different spectroscopic techniques. The objective of the current study was to assess the anti-inflammatory potential of melengestrol acetate (1), and its metabolites 2-5. The metabolites and the substrate were assessed for their inhibitory effects on proliferation of T-cells in vitro. The substrate (IC = 2.77 ± 0.08 µM) and its metabolites 2 (IC = 2.78 ± 0.07 µM), 4 (IC = 2.74 ± 0.1 µM), and 5 (IC = < 2 µM) exhibited potent T- cell proliferation inhibitory activities, while compound 3 (IC = 29.9 ± 0.09 µM) showed a moderate activity in comparison to the standard prednisolone (IC = 9.73 ± 0.08 µM). All the metabolites were found to be non-toxic against 3T3 normal cell line. This study thus identifies some potent compounds active against T-cell proliferation. Their anti-inflammatory potential, therefore, deserves to be further investigated.
Topics: 3T3 Cells; Animals; Biotransformation; Cell Proliferation; Dose-Response Relationship, Drug; Fermentation; Humans; Melengestrol Acetate; Mice; Molecular Structure; Phyllachorales; Rhizopus; Seeds; Structure-Activity Relationship; T-Lymphocytes
PubMed: 33142425
DOI: 10.1016/j.bioorg.2020.104313 -
Zoo Biology Jan 2022Giraffe present unique contraception challenges as males persistently pursue females during estrus. Year-round pursuit during frequent recurring estrus can pose...
Giraffe present unique contraception challenges as males persistently pursue females during estrus. Year-round pursuit during frequent recurring estrus can pose significant risk under slippery conditions. Complete ovarian suppression is a useful tool in giraffe because it eliminates estrous behavior, interest from the male, and controls reproduction. Effective reproduction control in giraffes has been achieved with porcine zona pellucida, oral melengestrol acetate, and depot medroxy-progesterone acetate. However, these methods allow some degree of folliculogenesis and estrous behavior. Improvest® is a gonadotropin releasing hormone (GnRH) immunological product that elicits antibodies against GnRH and abrogates the effects of endogenous GnRH. This study evaluated the efficacy of Improvest® for gonadal suppression in seven females and one male giraffe by monitoring steroid hormones. Seven female giraffe were treated intramuscularly with an initial dose, a booster at 4 weeks and maintenance boosters at 3-month intervals (600 µg/dose) for 12 months. Six females were on supplemental contraception during the induction phase because separation from males was not possible. In the male (treated with 400 µg), testosterone concentrations decreased after the second injection. However, even with low serum testosterone concentrations, mounting (of nontreated females) behavior was still observed occasionally. Ovarian activity was suppressed in all treated females and interest by the males stopped; supplemental contraceptives (during the induction phase) did not impede the effect of Improvest®. After 15.3 months (seven doses), Improvest® was discontinued in three females which no longer needed contraception. In these females, ovarian activity was noted approximately 90 days after the last dose.
Topics: Animals; Animals, Zoo; Contraception, Immunologic; Female; Giraffes; Gonadotropin-Releasing Hormone; Male; Reproduction; Swine
PubMed: 34529298
DOI: 10.1002/zoo.21652 -
Journal of Biomolecular Structure &... Apr 2022Growth hormones (GH) have diverse functions like growth promotion, metabolism, appetite, reproduction and social behavior in vertebrates, which is mediated through the...
Growth hormones (GH) have diverse functions like growth promotion, metabolism, appetite, reproduction and social behavior in vertebrates, which is mediated through the growth hormone receptor (GHR). This work was aimed to analyze structural features, homology modeling and molecular docking of GHR protein. A physicochemical characteristic, like molecular weight was 67.2 kDa and hydropathicity was 0.336. Protein modeling and structure confirmation of GHR protein showed 92.7% residues are in the favored region. Selection of ligands and molecular docking shown Melengestrol and Riboflavin ligand showed uppermost binding energy values -7.8 and -7.3 kcal/mol. Molecular interactions describe conventional hydrogen bonding of Melengestrol was observed with VAL94, GLU97, GLU95, TRP57, PHE33, THR34, PRO35, ASP36, PRO37, ARG49, GLY292, LYS291, ILE290, ALA287, LYS289 residues. Riboflavin hydrogen bonds interaction was at PRO37, ASP36, PRO35, THR34, ARG49, SER144, VAL443, GLN442, PRO284, ASP294, ILE285, PRO286, SER408, ALA287, GLY292, LYS291, ILE290, PRO288, LYS287. Molecular dynamics simulation outcomes revealed that complex 2 (Riboflavin and GHR protein) is better than complex1 (Melengestrol and GHR protein). Overall, the results of the present work lead identification of novel molecules that may be agonistic of growth hormone receptor protein and can be used to surge growth in fish. Communicated by Ramaswamy H. Sarma.
Topics: Animals; Cyprinidae; Growth Hormone; Ligands; Melengestrol Acetate; Molecular Docking Simulation; Receptors, Somatotropin; Riboflavin
PubMed: 33179589
DOI: 10.1080/07391102.2020.1844063 -
Zoo Biology Mar 2021Melengestrol acetate (MGA) implants are progestin-based reversible contraceptives used to manage fertility in zoo populations. Although it is recommended that MGA...
Melengestrol acetate (MGA) implants are progestin-based reversible contraceptives used to manage fertility in zoo populations. Although it is recommended that MGA implants should be replaced every 2 years, the duration of efficacy has not been systematically evaluated in most species. Anecdotal reports for Old World monkeys indicate that reproduction may be suppressed longer if the implant is not removed. This study uses Guereza colobus monkey (Colobus guereza) as a model Old World monkey species to examine the effects of MGA implants on reproductive potential. In particular, we investigate whether the probability of reproducing (pR) and rates of stillbirth differ among (1) non-implanted females, (2) females who have had MGA implants removed, and (3) females whose implants were left in past expiration. We found no significant difference in pR between non-implanted and implant-removed groups, but when implants were left in past expiration, the pR was significantly lower than in other groups. Both parity and age significantly impacted pR for the non-implanted group (i.e., younger females and those who were parous increased pR), but neither were significant factors for the implant-removed group. Stillbirth rates were significantly higher post-contraception as compared with pre-contraception. These results support similar analyses in other taxa that show a shorter time to reversal after MGA contraception when implants are removed, making this a good contraceptive option for females likely to receive a breeding recommendation, especially when a more predictable time to reversal is important.
Topics: Animals; Animals, Zoo; Colobus; Contraception; Contraceptive Agents, Female; Drug Implants; Female; Melengestrol Acetate; Pregnancy; Reproduction; Stillbirth
PubMed: 33238048
DOI: 10.1002/zoo.21581 -
Animal Reproduction Science Sep 2023This study aimed to evaluate minimally invasive protocols for estrus synchronization in the brown brocket deer (Subulo gouazoubira). Females were submitted to Latin...
This study aimed to evaluate minimally invasive protocols for estrus synchronization in the brown brocket deer (Subulo gouazoubira). Females were submitted to Latin square design, in different treatments. All females received 0.25 mg of estradiol benzoate on the first day of treatment, concomitant with one of the following sources of progesterone: (1) DIP: an intravaginal progesterone releasing device for eight days, (2) MGA1x: once a day (in the morning) oral dose of 1 mg melengestrol acetate for eight days, (3) MGA2x: twice a day (morning and afternoon) oral doses of 0.5 mg of MGA for eight days, (4) P4LA: a single i.m. administration of 75 mg of long-acting progesterone (P4LA). Eight days after the beginning of each treatment, females received an i.m. administration of 265 µg of prostaglandin (PGF; cloprostenol). Treatment efficacy was evaluated by manifestation of behavioral estrus after treatment and concentration of fecal progesterone metabolites (FPM). The time to onset of estrus in treatment P4LA was significantly longer (180 ± 38.9 h) compared to DIP (63 ± 6.6 h), MGA1x (53 ± 14.4 h) and MGA2x (41 ± 10.1 h) (P = 0.008). According to individual baseline FPM and FPM concentration during the days after estrus, the corpus luteum formation was suggested in all females which responded to the treatments (93.75 %). Low synchrony, longer interval between PGF administration and onset of estrus suggest that the P4LA dose (75 mg) is too high and not effective for S. gouazoubira. DIP, MGA 1x and MGA 2x, were effective in estrus synchronization.
Topics: Female; Animals; Progesterone; Estrus Synchronization; Deer; Estrus; Estradiol; Melengestrol Acetate; Dinoprost; Insemination, Artificial
PubMed: 37603946
DOI: 10.1016/j.anireprosci.2023.107320 -
Shokuhin Eiseigaku Zasshi. Journal of... 2024The present study verified that it is possible to analyze melengesterol acetate using the existing multi-residue method. Melengestrol acetate was extracted from...
The present study verified that it is possible to analyze melengesterol acetate using the existing multi-residue method. Melengestrol acetate was extracted from livestock products using acidic acetonitrile acidified with acetic acid in the presence of n-hexane and anhydrous sodium sulfate. The crude extracts were cleaned up using an octadecylsilanized silica gel cartridge column. Separation by HPLC was performed using an octadecylsilanized silica gel column with linear gradient elution of 0.1 vol% formic acid and acetonitrile containing 0.1 vol% formic acid. For the determination of the analyte, tandem mass spectrometry with positive ion electrospray ionization was used. In recovery tests using four livestock products fortified with maximum residue limits levels of melengestrol acetate (0.001-0.02 mg/kg), the truenesses ranged from 82% to 100%, and the repeatabilities for the entire procedure ranged from 0.5 RSD% to 5.6 RSD%. In recovery tests using 11 livestock products fortified with 0.0005 mg/kg of melengestrol acetate, the truenesses ranged from 88% to 99%, and the repeatabilities ranged from 1.3 RSD% to 5.4 RSD%. The limit of quantification for melengestrol acetate in livestock products was 0.0005 mg/kg.
Topics: Animals; Liquid Chromatography-Mass Spectrometry; Melengestrol Acetate; Chromatography, Liquid; Livestock; Silica Gel; Tandem Mass Spectrometry; Acetonitriles; Formates
PubMed: 38432897
DOI: 10.3358/shokueishi.65.15 -
Journal of Agricultural and Food... Jun 2023Gestagens, a class of veterinary drugs also called progestogens, are synthetic hormones used to increase feed efficiency and rate of gain in heifers. The Canadian Food...
Gestagens, a class of veterinary drugs also called progestogens, are synthetic hormones used to increase feed efficiency and rate of gain in heifers. The Canadian Food Inspection Agency analyzes progestogens melengestrol acetate (MGA), megestrol acetate, and chlormadinone acetate using liquid chromatography-mass spectrometry (LC-MS). Our conventional gestagen method for kidney fat has many time-consuming steps, including solid-phase extraction. A sample preparation procedure having fewer clean-up steps was developed for routine diagnostic analysis of kidney fat and provided similar results faster, and at lower cost. A confirmatory liver method for gestagens, developed using salt-assisted extraction, employed minimal clean-up steps that resulted in high chemical background at the desired lower limit of quantification (LLOQ). Differential ion mobility spectrometry, specifically high-field asymmetric waveform ion mobility spectrometry (FAIMS), was used to filter chemical background in the gas phase. The effect of the ionization probe position on FAIMS parameters, including sensitivity, is described. With LC-FAIMS-MS, chemical background for each gestagen was virtually eliminated, resulting in a quantitative liver method having the desired 0.6 ng/g LLOQ and estimated limits of detection (LODs) up to 140 times lower than LC-MS. Incurred MGA samples, analyzed using kidney fat and liver methods from the same animal, show levels within the quantitative ranges of both methods.
Topics: Animals; Cattle; Female; Progestins; Canada; Chromatography, Liquid; Mass Spectrometry; Melengestrol Acetate; Liver
PubMed: 37319426
DOI: 10.1021/acs.jafc.3c01200