Effects of acaricides on the activities of monooxygenases in bovine liver microsomes.

Organophosphates (OPs), pyrethrins and fipronil, are acaricides commonly used in cattle, mainly as pour on formulations. Scant information is available on their potential interactions with hepatic xenobiotic metabolizing enzymes. This work aimed to evaluate in vitro the potential inhibitory effects of widely employed acaricides on catalytic activities mediated by hepatic cytochrome P450 (CYP) and flavin-monooxygenase (FMO) enzymes in cattle. Bovine (n = 4) liver microsomes were incubated in the absence (control assays) and in presence of different OPs (fenthion, chlorpyrifos, ethion, diazinon and dichlorvos), fipronil and cypermethrin at 0.1-100 µm. Five oxidative enzyme activities were assayed by spectrofluorimetric or HPLC methods: 7-ethoxyresorufin O-deethylase (for CYP1A1), methoxyresorufin O-demethylase (for CYP1A2), benzyloxyresorufin O-debenzylase (for CYP2B), testosterone 6-beta hydroxylase (for CYP3A) and benzydamine N-oxidase (for FMO). All acaricides, particularly phosphorothionate-containing OPs, inhibited to some extent more than one enzyme activity. The most frequent inhibitor was fenthion, which inhibited (p < .05) all enzyme activities tested (from 22% at 1 µm to 72% at 100 µm). However, low inhibitory potencies (IC50s higher than 7 µm) of all acaricides studied were observed against the catalytic activities assayed. Therefore, the risk of in vivo metabolic interactions due to inhibition of monooxygenases would be low under common husbandry conditions.

Metabolic stability of glyphosate and its environmental metabolite (aminomethylphosphonic acid) in the ruminal content of cattle.

Glyphosate (GLY) is one of the most commonly used herbicides worldwide. Both GLY and aminomethylphosphonic acid (AMPA), its main degradation product, may be present in feedstuffs offered to dairy cows. Although the major proportions of ingested GLY and AMPA are eliminated with faeces, a potential degradation of GLY to AMPA in the rumen of dairy cows has been suggested. Considering that the rumen plays a central role in the pre-systemic metabolism of xenobiotics, this research aimed to investigate whether or not GLY and AMPA are metabolised in the ruminal environment of cattle. The distribution of both compounds between the fluid and solid phases of the ruminal content (RC) was also evaluated. RC from 3 steers were collected in an abattoir. Aliquots were incubated (3-6 h) in anaerobiosis with GLY (15 µg/mL) and AMPA (1.5 µg/mL). Metabolic viability of RC was assessed by the measurement of the sulpho-reduction of the anthelmintic derivative albendazole sulphoxide (ABZSO) into albendazole (ABZ) in the absence (controls) or in presence of GLY and AMPA. Incubations of boiled (inactive) RC were used as controls. Samples were analysed by HLPC with fluorescence detection. Neither GLY nor AMPA were metabolised in metabolically active RC from cattle. Both compounds were predominantly found in the fluid phase compared to the solid (particulate) matter of RC. Neither GLY nor AMPA had a negative effect on the metabolic production of ABZ. A high metabolic stability of both compounds within the ruminal environment would be expected in vivo. Their presence in high proportion in the fluid phase of the ruminal content may give rise to a rapid flow of both GLY and AMPA to the posterior gastrointestinal tract. Negative effects on the ruminal biotransformation of therapeutically used drugs would not be expected when the herbicide and its degradation product are consumed with food.

Fungal colonization associated with phenological stages of a photosynthetic terrestrial temperate orchid from the Southern Iberian Peninsula.

Fungal endophytes, both mycorrhizal and non-mycorrhizal, are involved in the development of the life cycle of orchids, providing potential beneficial relationships. Here, we assess the succession of changes in the diversity of fungal symbionts associated with a terrestrial temperate orchid species, Anacamptis morio subsp. champagneuxii, over three phenological stages: developed leaves but no stem elongation, flowering, and fruiting. Fungi endophyte associated with roots were obtained by culture in sterile conditions. A total of 18 morphotypes-one Mortierellomycota, two Basidiomycota and 15 Ascomycota-were differentiated, and were also characterized using PCR and DNA sequencing techniques. Only three of the 18 OTUs are shared among the three phenological stages examined: Westerdykella sp., a member of Ceratobasidiaceae, and Fusarium oxysporum, representing a relative abundance of between 28% (fruiting) to 41% (flowering). Our research confirmed that fungal symbionts varied among the different phenological stages examined, the peak of endophyte diversity appearing in the flowering stage. The availability of a diverse mycobiota seems to be important for the survival of orchid plants because it may cover particular physiological needs, and knowledge concerning this mycobiota is of special relevance in the establishment of reliable conservation programmes.

Quinolones Modulate Ghrelin Receptor Signaling: Potential for a Novel Small Molecule Scaffold in the Treatment of Cachexia.

Cachexia is a metabolic wasting disorder characterized by progressive weight loss, muscle atrophy, fatigue, weakness, and appetite loss. Cachexia is associated with almost all major chronic illnesses including cancer, heart failure, obstructive pulmonary disease, and kidney disease and significantly impedes treatment outcome and therapy tolerance, reducing physical function and increasing mortality. Current cachexia treatments are limited and new pharmacological strategies are needed. Agonists for the growth hormone secretagogue (GHS-R1a), or ghrelin receptor, prospectively regulate the central regulation of appetite and growth hormone secretion, and therefore have tremendous potential as cachexia therapeutics. Non-peptide GHS-R1a agonists are of particular interest, especially given the high gastrointestinal degradation of peptide-based structures, including that of the endogenous ligand, ghrelin, which has a half-life of only 30 min. However, few compounds have been reported in the literature as non-peptide GHS-R1a agonists. In this paper, we investigate the in vitro potential of quinolone compounds to modulate the GHS-R1a in both transfected human cells and mouse hypothalamic cells. These chemically synthesized compounds demonstrate a promising potential as GHS-R1a agonists, shown by an increased intracellular calcium influx. Further studies are now warranted to substantiate and exploit the potential of these novel quinolone-based compounds as orexigenic therapeutics in conditions of cachexia and other metabolic and eating disorders.

Protein and amino acid composition of select wild legume species of tribe Fabeae.

The nutritional characteristics of seed proteins of 50 Spanish wild taxa of Lathyrus, Lens, Pisum and Vicia have been compared. The highest average protein richness and the in vitro protein digestibility have been observed in the genus Vicia and Lens, respectively, whereas the genus Pisum showed the lowest protein-digestibility corrected amino acid score. Using the K-means algorithm three clearly distinguished groups of taxa have been established in relation to their essential amino acid contents, protein richness, digestibility and nutritional parameters. The most adequate protein profile was observed in the taxa of group 1. This group includes four taxa of genus Lathyrus and nine taxa of genus Vicia. It should be noted that seven of the thirteen taxa included in this group have never been used as crops.

Nutritional characteristics of seed proteins in 28 Vicia species (Fabaceae) from Southern Spain.

The study of local plants could provide useful data for the possible development of future crops with good nutritional and functional properties. The nutritional characteristics of the seed proteins of 28 Vicia species (31 taxa) (Fabaceae) from Spain were studied. Protein contents in studied Vicia ranged from 20.1% in V. articulata to 32% in V. pyrenaica. V. altissima, which is only deficient in Trp, showed the most balanced amino acid composition, while the remaining taxa were limiting in Met, Cys, and Trp. In vitro protein digestibility (IVPD) ranged from 78% in V. incana to 86.3% in V. hirsuta. In addition to the amino acid composition and IVPD, other nutritional parameters, such as amino acid score, biological value, protein efficiency ratio, or protein digestibility corrected amino acid score, were studied. Results confirm the interest of studying wild populations of cultivated and non cultivated Vicia species as potentially interesting sources of seeds with good nutritional characteristics.