A novel LC–MS/MS assay for the simultaneous determination of melatonin and its two major metabolites, 6-hydroxymelatonin and 6-sulfatoxymelatonin in dog plasma: Application to a pharmacokinetic study

Zhao, Huimin; Wang, Yifei; Yuan, Bo; Liu, Shu; Man, Shuang; Xu, Haiyan; Lu, Xiumei

doi:10.1016/j.jpba.2015.09.028

Cited by 21 publications

(12 citation statements)

References 27 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Our study evaluated 10 dogs, which is similar to study population sizes in other pharmacodynamic studies used to assess medication effects on IL‐2 and IFN‐γ levels via identical laboratory methods (Fellman et al., ; Riggs et al., ), and slightly more than the typical six to eight animals utilized in comparable pharmacokinetic trials for a drug with normal variability (Riviere, ). As observed in other studies (Ashley et al., ; Frank, Hnilica, & Oliver, ; Zhao et al., ), no adverse side effects were noted in any of the study participants.…”

Section: Discussionsupporting

confidence: 85%

“…Melatonin pharmacokinetics in dogs have been reported in drug manufacturer studies to be approximately comparable to humans, with peak drug levels attained within 1–2 hr of drug administration and an elimination half‐life of approximately 30 min (European Medicines Agency, ; Therapeutic Goods Administration, ). Although oral melatonin absorption has been previously evaluated in human, rodent, primate, and canine studies (Ashley et al., ; Harpsøe, Andersen, Gögenur, & Rosenberg, ; Yeleswaram, McLauglin, Knipe, & Schabdach, ; Zhao et al., ), the authors are unaware of any studies that determine the minimum plasma concentrations of melatonin or its metabolites that are required for pharmacodynamic effects. For the reference laboratory used in this study to measure blood melatonin concentrations (NMS Lab), an oral dose of 6 mg in people was reported to produce an average peak (approximately 1 hr after drug administration) blood drug level of 12 ng/ml, although ideal target concentrations for treatment of conditions for which the drug is generally indicated (sleep disorders, for example) are not well established.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Pharmacodynamic evaluation of the effects of oral melatonin on expression of the T‐cell cytokines interleukin‐2 and interferon gamma in the dog

Peace¹,

Kumar

Wills

et al. 2019

Vet Pharm & Therapeutics

View full text Add to dashboard Cite

Objective To determine the effects of exogenous melatonin administration on activated whole blood expression of the T‐cell cytokines interleukin‐2 (IL‐2) and interferon gamma (INF‐γ) in dogs. Animals Ten healthy dogs. Procedures Heparinized whole blood was collected from 10 dogs for analysis of cytokine expression before administration of melatonin (baseline). Each dog was then administered melatonin at a dosage of approximately 1 mg/kg, PO, q 12 hr for 14 days. On day 14, whole blood was again collected from each dog at the time points of trough (0 hr) and 6 hr postmelatonin administration to evaluate the effects of melatonin on cytokine expression. At all evaluated time points, analysis of activated whole blood expression of mRNA coding for both IL‐2 and IFN‐γ was performed using quantitative reverse transcription polymerase chain reaction to determine whether a difference existed for any time point. Blood melatonin concentrations were also measured at comparable time points. Results A statistical difference in the expression of either cytokine was not appreciated at any time point, despite attainment of expected blood concentrations of the drug. Conclusions and Clinical Relevance Results indicate that melatonin therapy does not significantly affect IL‐2 or IFN‐γ expression in healthy dogs. While melatonin is thought to have an effect on the immune system in dogs, it does not appear this effect is through altering T‐cell IL‐2 or IFN‐γ expression. Further studies investigating the effects of melatonin on the immune system of dogs are warranted.

show abstract

Section: Discussionsupporting

confidence: 85%

Section: Discussionmentioning

confidence: 99%

Pharmacodynamic evaluation of the effects of oral melatonin on expression of the T‐cell cytokines interleukin‐2 and interferon gamma in the dog

Peace¹,

Kumar

Wills

et al. 2019

Vet Pharm & Therapeutics

View full text Add to dashboard Cite

show abstract

“…The concentration of this melatonin biomarker in urine was associated with the plasmatic concentration of melatonin (r = 0.926, p < 0.05). After intake, melatonin is promptly transformed in 6-hydroxymelatonin, being further conjugated, giving rise to aMT6s [61]. The concentration of aMT6s excreted in urine after lentil extract and melatonin intake confirmed the highly efficient metabolism of melatonin in rats [62].…”

Section: Lentil Sprouts Intake Greater Elevate Melatonin Biomarkers Tmentioning

confidence: 69%

Bioavailability of Melatonin from Lentil Sprouts and Its Role in the Plasmatic Antioxidant Status in Rats

Rebollo‐Hernanz

Aguilera

Herrera

et al. 2020

Foods

View full text Add to dashboard Cite

Melatonin is a multifunctional antioxidant neurohormone found in plant foods such as lentil sprouts. We aim to evaluate the effect of lentil sprout intake on the plasmatic levels of melatonin and metabolically related compounds (plasmatic serotonin and urinary 6-sulfatoxymelatonin), total phenolic compounds, and plasmatic antioxidant status, and compare it with synthetic melatonin. The germination of lentils increases the content of melatonin. However, the phenolic content diminished due to the loss of phenolic acids and flavan-3-ols. The flavonol content remained unaltered, being the main phenolic family in lentil sprouts, primarily composed of kaempferol glycosides. Sprague Dawley rats were used to investigate the pharmacokinetic profile of melatonin after oral administration of a lentil sprout extract and to evaluate plasma and urine melatonin and related biomarkers and antioxidant capacity. Melatonin showed maximum concentration (45.4 pg/mL) 90 min after lentil sprout administration. The plasmatic melatonin levels increased after lentil sprout intake (70%, p < 0.05) with respect to the control, 1.2-fold more than after synthetic melatonin ingestion. These increments correlated with urinary 6-sulfatoxymelatonin content (p < 0.05), a key biomarker of plasmatic melatonin. Nonetheless, the phenolic compound content did not exhibit any significant variation. Plasmatic antioxidant status increased in the antioxidant capacity upon both lentil sprout and synthetic melatonin administration. For the first time, we investigated the bioavailability of melatonin from lentil sprouts and its role in plasmatic antioxidant status. We concluded that their intake could increase melatonin plasmatic concentration and attenuate plasmatic oxidative stress.

show abstract

“…Supernatant was collected, vacuum-dried, and stored at −80°C until analysis was performed. Chromatography was performed using an Imtakt Intrada amino acid column (3 µm, 2 × 150 mm; (Chrom Tech Inc., Apple Valley, MN) as described and modified (Zhao et al, 2016). A standard curve was used to calculate melatonin concentrations (R 2 = 0.99).…”

Section: Blood Sampling and Analysis Of Glucose Bhb Nefa Insulin mentioning

confidence: 99%

Exposure to chronic light–dark phase shifts during the prepartum nonlactating period attenuates circadian rhythms, decreases blood glucose, and increases milk yield in the subsequent lactation

Suárez-Trujillo

Wernert

Sun

et al. 2020

Journal of Dairy Science

View full text Add to dashboard Cite

Maintaining metabolic balance is a key factor in the health of dairy cattle during the transition from pregnancy to lactation. Little is known regarding the role of the circadian timing system in the regulation of physiological changes during the transition period. We hypothesized that disruption of the cow's circadian timing system by exposure to chronic light-dark phase shifts during the prepartum period would negatively affect the regulation of homeostasis and cause metabolic disturbances, leading to reduced milk production in the subsequent lactation. The objective was to determine the effect of exposure to chronic light-dark phase shift during the last 5 wk prepartum of the nonlactating dry period on core body temperature, melatonin, blood glucose, β-hydroxybutyric acid (BHB) and nonesterified fatty acid (NEFA) concentrations, and milk production. Multiparous cows were moved to tiestalls at 5 wk before expected calving and assigned to control (CTR; n = 16) or phase-shifted (PS; n = 16) treatments. Control cows were exposed to 16 h of light and 8 h of dark. Phase-shifted cows were exposed to the same photoperiod; however, the light-dark cycle was shifted 6 h every 3 d until parturition. Resting behavior and feed intake were recorded daily. Core body temperature was recorded vaginally for 48 h at 23 and 9 d before expected calving using calibrated data loggers. Blood concentrations of melatonin, glucose, BHB, and NEFA were measured during the pre-and postpartum periods. Milk yield and composition were measured through 60 DIM. Treatment did not affect feed intake or body condition. Cosine fit analysis of 24-h core body temperature and circulating melatonin indicated attenuation of circadian rhythms in the PS treatment compared with the CTR treatment. Phase-shifted cows had lower rest consolidation, as indicated by more total resting time, but shorter resting period durations. Phase-shifted cows had lower blood glucose concentration compared with CTR cows (4 mg/mL decrease), but BHB and NEFA concentrations were similar between PS and CTR cows. Milk yield and milk fat yield were greater in PS compared with CTR cows (2.8 kg/d increase). Thus, exposure to chronic light-dark phase shifts during the prepartum period attenuated circadian rhythms of core body temperature, melatonin, and rest-activity behavior and was associated with increased milk fat and milk yield in the postpartum period despite decreased blood glucose pre-and postpartum. Therefore, less variation in central circadian rhythms may create a more constant milieu that supports the onset of lactogenesis.

show abstract

A novel LC–MS/MS assay for the simultaneous determination of melatonin and its two major metabolites, 6-hydroxymelatonin and 6-sulfatoxymelatonin in dog plasma: Application to a pharmacokinetic study

Cited by 21 publications

References 27 publications

Pharmacodynamic evaluation of the effects of oral melatonin on expression of the T‐cell cytokines interleukin‐2 and interferon gamma in the dog

Pharmacodynamic evaluation of the effects of oral melatonin on expression of the T‐cell cytokines interleukin‐2 and interferon gamma in the dog

Bioavailability of Melatonin from Lentil Sprouts and Its Role in the Plasmatic Antioxidant Status in Rats

Exposure to chronic light–dark phase shifts during the prepartum nonlactating period attenuates circadian rhythms, decreases blood glucose, and increases milk yield in the subsequent lactation

Contact Info

Product

Resources

About