Mel Group Research Articles

Short-Term Treatment of Melatonin Improves the Expression of Cell Adhesion Molecules in the Testis of the Mouse Cryptorchidism Model.

Melatonin plays a major role in regulating the sleep-wake cycle and enhancing testosterone production. We investigated the short-term effects of melatonin treatment for 14 consecutive days in the cryptorchidism model. We categorized experimental mice into Sham (S), Orchiopexy (O), Melatonin (Mel), and Orchiopexy + Melatonin (OMel) groups. Surgery involved inducing cryptorchidism in the left testis for seven days, followed by orchiopexy. The Mel group's testes did not descend, but they received melatonin injections after seven days of cryptorchidism. The OMel group underwent both orchiopexy and melatonin treatment. Both O and Mel groups exhibited decreased sperm and round-headed sperm in the epididymis. Significant increases were observed in the numbers of giant cells and negative Nectin-3 cells at p-value<0.05. The pattern of Cadm1 expression changed, and Nectin-2 and Nectin-3 co-expression was lacking in abnormal spermatids. Sertoli cell cytoplasm in both O and Mel groups exhibited autophagosomes and multivesicular bodies, which correlated with increased cyclooxygenase-2 expression. However, Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL)-positive cell numbers increased significantly in all treatment groups compared to the S group. Our study found that the combination of orchiopexy and melatonin positively influenced the expression of cell adhesion molecules (Cadm1, Nectin-2, and Nectin-3) involved in spermatogenesis, while reducing giant cells, autophagosomes, and apoptosis.

Exogenous melatonin ameliorates embryo-maternal cross-talk in early pregnancy in sheep.

Melatonin plays a crucial role in enhancing reproductive performance in small ruminants. This paper reveals the effects of exogenous melatonin on the placental and endometrial rearrangement in early pregnancy in sheep. Early pregnancy losses cause 25% of pregnancy failures in small ruminants because of asynchrony between conceptus and uterine signals. In this context, melatonin plays a crucial role in sheep reproductive dynamics, but little is known about its effects during the peri-implantation period. We hypothesized that melatonin supports embryo implantation by modulating the uterine microenvironment. This study aimed to assess the effects of exogenous melatonin on the endometrial and early placental rearrangement. Ten multiparous ewes either did (MEL, n = 5) or did not (CTR, n = 5) receive a subcutaneous melatonin implant (18 mg) 50 days before a synchronized mating. On day 21 of pregnancy, the sheep were euthanized. MEL ewes exhibited a higher prolificity rate (2.8 vs 2.0 embryos/ewe) and plasma progesterone levels (3.84 vs 2.96 ng/mL, P < 0.05) than did CTR ewes. Groups did not differ significantly in embryo crown-rump length. MEL placentas had significantly (P < 0.001) more binucleated trophoblast cells in the chorion region, and ovine placental lactogen expression was significantly (P < 0.05) more strongly upregulated than in CTR. Exogenous melatonin increased significantly (P < 0.05) gene expression of angiogenic factors (VEGFA, VEGFR1, IGF1R), IFNAR2, and PR in the caruncular endometrium. Expression of the MT2 receptor in the endometrium and placenta was significantly (P < 0.05) higher in the MEL group. These results indicate that melatonin implants acted differentially on uterine and placental rearrangement. Melatonin increases differentiation in the placenta and induces changes that could promote vessel maturation in the endometrium, suggesting that it enhances the uterine microenvironment in the early stage of pregnancy in sheep.

Comparing the efficacy of 308-nm light-emitting diode and 308-nm excimer lamp for treating vitiligo: A randomized controlled trial.

In previous studies, the 308-nm light-emitting diode (LED) has been proven safe and effective for treating vitiligo. However, direct comparisons between the 308-nm LED and 308-nm excimer lamp (308-nm MEL) for the treatment of vitiligo are lacking. To compare the efficacy of the 308-nm LED and 308-nm MEL for treating nonsegmental stable vitiligo. This randomized controlled trial was conducted between January 2018 and August 2023. Enrolled patients were randomly assigned to either the 308-nm LED or the 308-nm MEL groups, both receiving 16 treatment sessions. Adverse events that occurred during the treatment were documented. In total, 269 stable vitiligo patches from 174 patients completed the study. A total of 131 lesions were included in the 308-nm LED group, and 138 lesions were included in the 308-nm MEL group. After 16 treatment sessions, 38.17% of the vitiligo patches in the 308-nm LED group achieved repigmentation of at least 50% versus 38.41% in the 308-nm MEL group. The two devices exhibited similar results in terms of efficacy for a repigmentation of at least 50% (p = .968). The incidence of adverse effects with the two phototherapy devices was comparable (p = .522). Treatment of vitiligo with the 308-nm LED had a similar efficacy rate to the 308-nm MEL, and the incidence of adverse effects was comparable between the two devices.

Effect of melatonin on developmental competence, mitochondrial distribution, and intensity of fresh and vitrified/thawed in vitro matured buffalo oocytes

Background: In livestock breeding, oocyte cryopreservation is crucial for preserving and transferring superior genetic traits. This study was conducted to examine the additional effect of melatonin to maturation and vitrification media on the in vitro developmental capacity, mitochondrial distribution, and intensity of buffalo oocytes. The study involved obtaining ovaries from a slaughterhouse and conducting two phases. In the first phase, high-quality oocytes were incubated in a maturation medium with or without 10−9M melatonin for 22 h (at 38.5°C in 5% CO2). Matured oocytes were fertilized in vitro and cultured in SOF media for seven days. In the second phase, vitrified in vitro matured oocytes were stored in vitrified media (basic media (BM) containing a combination of cryoprotectants (20% Ethyl Glycol and 20% Dimethyl sulfoxide), with or without melatonin, and then stored in liquid nitrogen. Normal vitrified/thawed oocytes were fertilized in vitro and cultured as described. Finally, the matured oocytes from the fresh and vitrified/thawed groups, both with and without melatonin, were stained using DAPI and Mitotracker red to detect their viability (nuclear maturation), mitochondrial intensity, and distribution using a confocal microscope. The study found that adding 10−9M melatonin to the maturation media significantly increased maturation (85.47%), fertilization rate (84.21%)cleavage (89.58%), and transferable embryo (48.83%) rates compared to the group without melatonin (69.85%,79.88%, 75.55%, and 37.25% respectively). Besides that, the addition of melatonin to the vitrification media improved the recovery rate of normal oocytes (83.75%), as well as the cleavage (61.80%) and transferable embryo (27.00%) rates when compared to the vitrified TCM group (67.46%, 51.40%, and 17.00%, respectively). The diffuse mitochondrial distribution was higher in fresh with melatonin (TCM + Mel) (80%) and vitrified with melatonin (VS2 + Mel groups) (76.70%), Furthermore, within the same group, while the mitochondrial intensity was higher in the TCM + Mel group (1698.60) than other group. In conclusion, Melatonin supplementation improves the developmental competence and mitochondrial distribution in buffalo oocytes in both cases(in vitro maturation and vitrification).

Melatonin reduces lung injury in type 1 diabetic mice by the modulation of autophagy

BackgroundIn recent years, the role of autophagy has been highlighted in the pathogenesis of diabetes and inflammatory lung diseases. In this study, using a diabetic model of mice, we investigated the expression of autophagy-related genes in the lung tissues following melatonin administration.ResultsData showed histopathological remodeling in lung tissues of the D group coincided with an elevated level of IL-6, Becline-1, LC3, and P62 compared to the control group (p < 0.05). After melatonin treatment, histopathological remodeling was improved D + Mel group. In addition, expression levels of IL-6, Becline-1, LC3, and P62 were decreased in D + Mel compared to D group (P < 0.05). Statistically significant differences were not obtained between Mel group and C group (p > 0.05).ConclusionOur results showed that melatonin injection can be effective in the amelioration of lung injury in diabetic mice presumably by modulating autophagy-related genes.

Efficacy of biologically-directed daylight therapy on sleep and circadian rhythm in Parkinson's disease: a randomised, double-blind, parallel-group, active-controlled, phase 2 clinical trial

New non-pharmacological treatments for improving non-motor symptoms in Parkinson's disease (PD) are urgently needed. Previous light therapies for modifying sleep behaviour lacked standardised protocols and were not personalised for an individual patient chronotype. We aimed to assess the efficacy of a biologically-directed light therapy in PD that targets retinal inputs to the circadian system on sleep, as well as other non-motor and motor functions. In this randomised, double-blind, parallel-group, active-controlled trial at the Queensland University of Technology, Australia, participants with mild to moderate PD were computer randomised (1:1) to receive one of two light therapies that had the same photometric luminance and visual appearance to allow blinding of investigators and participants to the intervention. One of these biologically-directed lights matched natural daylight (Day Mel), which is known to stimulate melanopsin cells. The light therapy of the other treatment arm of the study, specifically supplemented the stimulation of retinal melanopsin cells (Enhanced Mel), targeting deficits to the circadian system. Both lights were administered 30min per day over 4-weeks and personalised to an individual patient's chronotype, while monitoring environmental light exposure with actigraphy. Co-primary endpoints were a change from baseline in mean sleep macrostructure (polysomnography, PSG) and an endocrine biomarker of circadian phase (dim light melatonin secretion onset, DLMO) at weeks 4 and 6. Participants data were analysed using an intention to treat principle. All endpoints were evaluated by applying a mixed model analysis. The trial is registered with the Australian New Zealand Clinical Trials Registry, ACTRN12621000077864. Between February 4, 2021 and August 8, 2022, 144 participants with PD were consecutively screened, 60 enrolled and randomly assigned to a light intervention. There was no significant difference in co-primary outcomes between randomised groups overall or at any individual timepoint during follow-up. The mean (95% CI) for PSG, N3% was 24.15 (19.82-28.48) for Day Mel (n=23) and 19.34 (15.20-23.47) for the Enhanced Mel group (n=25) in week 4 (p=0.12); and 21.13 (16.99-25.28) for Day Mel (n=26) and 18.48 (14.34-22.62) for the Enhanced Mel group (n=25) in week 6, (p=0.37). The mean (95% CI) DLMO (decimal time) was 19.82 (19.20-20.44) for Day Mel (n=22) and 19.44 (18.85-20.04) for the Enhanced Mel group (n=24) in week 4 (p=0.38); and 19.90 (19.27-20.53) for Day Mel (n=23) and 19.04 (18.44-19.64) for the Enhanced Mel group (n=25) in week 6 (p=0.05). However, both the controlled daylight (Day Mel) and the enhanced melanopsin (Enhanced Mel) interventions demonstrated significant improvement in primary PSG sleep macrostructure. The restorative deep sleep phase (PSG, N3) significantly improved at week 6 in both groups [model-based mean difference to baseline (95% CI):-3.87 (-6.91 to-0.83), p=0.04]. There was a phase-advance in DLMO in both groups which did not reach statistical significance between groups at any time-point. There were no safety concerns or severe adverse events related to the intervention. Both the controlled daylight and melanopsin booster light showed efficacy in improving measures of restorative deep sleep in people with mild to moderate PD. That there was no significant difference between the two intervention groups may be due to the early disease stage. The findings suggest that controlled indoor daylight that is personalised to the individuals' chronotype could be effective for improving sleep in early to moderate PD, and further studies evaluating controlled daylight interventions are now required utilising this standardised approach, including in advanced PD. The Michael J Fox Foundation for Parkinson's Research, Shake IT Up Australia, National Health and Medical Research Council, and Australian Research Council.

Influence of photoperiod and exogenous melatonin on testis morpho-physiology of sexually mature guinea fowl (Numida meleagris)

The biological effects of simulated photoperiod and melatonin on the control of reproduction of guinea fowls (Numida meleagris) are not well understood. Herein, thirty (30) sexually mature guinea fowl cocks were randomly assigned to 1–6 groups (n = 5) and subjected to different photoperiodic regimes in the presence or absence of exogenous melatonin (Mel; 1 mg/kgBW/day, i/m) for eight weeks. Testes of the euthanized cocks were processed for gross morphology, histological, histochemical, and oxidative stress markers. Testosterone concentration was determined in serum samples using the enzyme-linked immunosorbent assay (ELISA) technique. We observed an increase in testicular size in the Mel and Non-Mel groups under long-day (LD) photoperiods, and in the Non-Mel group under short-day (SD) photoperiod. Conversely, the testicular size was drastically reduced in the Mel group for SD. Seminiferous tubules in the Mel and Non-Mel groups of the SD showed cytomorphological changes, including degenerated cells, focal vacuolations, and depletion of germinal epithelium. However, the germinal epithelium appeared to be complete and active in both the Mel and Non-Mel groups for the LD. In all groups, the testes showed positive staining for PAS with varying intensities. There was a significant difference in PAS-staining intensity between different photoperiodic regimes and exogenous melatonin. The study observed the interaction between photoperiods and exogenous melatonin on glutathione reductase (GSH), malondialdehyde (MDA), and serum testosterone. Overall, the results indicated that a long-day (LD) photoperiod, combined with exogenous melatonin, enhanced reproductive activity in male guinea fowl by increasing testicular size and serum testosterone concentration.

Evaluation of the effect of melatonin implantation in rams and eCG dose in ewes synchronized by a CIDR-eCG protocol on reproductive performance of Lacaune sheep breed during non-breeding season

Sustainable production of milk is favorable in dairy sheep industry, which necessitates year-round reproduction of rams and ewes even during non-breeding season. Hence, protocols facilitating reproduction of rams and ewes during non-breeding season are of importance for this purpose. Therefore, the present study was conducted to investigate the effect of melatonin implantation in rams and administration of 400 IU eCG (E400) versus 300 IU eCG (E300) in ewes on reproductive performance of Lacaune sheep breed during non-breeding season. Rams were allocated to two groups including untreated (control, CON; n = 36) and melatonin-treated (MEL; n = 37). A subset of rams from CON (n = 7) and MEL (n = 7) groups were used for assessment of scrotal circumference, kinematic and functional characteristics of sperm, total antioxidant capacity (TAC) of semen and circulating testosterone on Days 0 (the beginning of study) and 60 (60 days after melatonin implantation). Further, the study had a 2 × 2 factorial design with four experimental groups including 1) ewes treated with E300 and introduced to CON rams (E300CON; n = 17 rams and 172 ewes), 2) ewes treated with E300 and introduced to MEL rams (E300MEL; n = 18 rams and 177 ewes), 3) ewes treated with E400 and introduced to CON rams (E400CON; n = 19 rams and 192 ewes), and ewes treated with E400 and introduced to MEL rams (E400MEL; n = 19 rams and 190 ewes). Melatonin implantation improved scrotal circumference, concentration, progressive motility, velocity, mitochondrial membrane potential and viability of sperm, TAC of semen, concentration of testosterone and fertility of rams (P < 0.05). Besides, E400 compared with E300 enhanced synchronization of estrus and fertility in ewes (P < 0.05). In conclusion, melatonin implantation promoted reproductive performance in Lacaune rams, and increase in dose of eCG improved reproductive performance in Lacaune ewes.

Multi-parametric MRI assessment of melatonin regulating the polarization of microglia in rats after cerebral ischemia/reperfusion injury

ObjectivesMulti-parametric magnetic resonance imaging (MRI) can provide comprehensive and valuable information for precise diagnosis and treatment evaluation of a number of diseases. In this study, the neuroprotective effects of melatonin (Mel) on a rat model of cerebral ischemia/reperfusion injury (CIRI) were assessed by multi-parametric MRI combined with histopathological techniques for longitudinal monitoring of the lesion microenvironment. MethodsSixty Sprague Dawley (SD) rats were randomly divided into three groups: the Sham, CIRI and CIRI + Mel groups. At multiple time points after ischemia, MRI scanning was performed on a 7.0 Tesla MRI scanner. Multi-parametric MRI includes T2-weighted imaging (T2WI), diffusion weighted imaging (DWI), and chemical exchange saturation transfer (CEST)-MRI. CEST effects were calculated by the Lorentzian difference method, 3.5 ppm indicates amide protons of mobile proteins/peptide (Amide-CEST) and 2.0 ppm indicates amine protons (Guan-CEST). Multiple histopathological techniques were used to examine the histopathological changes and explore the therapeutic effects of Mel. ResultsT2WI and DWI-MRI could localize the infarct foci and areas in CIRI rats, which was further validated by staining, 2, 3, 5-triphenyl tetrazolium chloride (TTC) staining, hematoxylin and eosin (H&E) staining, and terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate-biotin nick end labelling (TUNEL) staining. After Mel treatment, T2WI and DWI-MRI showed smaller infarct volume, and neurons displayed improved morphology with less apoptosis rates. Notably, Amide-CEST and Guan-CEST signal decreased as early as 2 h after CIRI (all P <0.001), reflecting the change of pH after ischemia. After Mel treatment, both Amide-CEST and Guan-CEST signal increased in ischemic cortex and striatum compared with control group (all P < 0.001). The immunofluorescence staining and western blotting analysis suggested the expression of M2 microglia increased after Mel treatment; While，after Mel treatment the inflammatory factor interleukin-1β (IL-1β) decreased compared with control CIRI rats. ConclusionsMulti-parametric MRI was shown to be an effective method to monitor the brain damage in a rat model of CIRI and assess the therapeutic effects of Mel treatment. Amide-CEST and Guan-CEST were especially sensitive to the changes in brain microenvironment during the early stage after CIRI. Furthermore, the neuroprotective effect of Mel treatment is associated with its promotion of the microglia polarized to M2 type in CIRI rats.

PSII-2 Evaluation of Meloxicam in Sows Post-Farrowing on Sow and Piglet Performance

Abstract Meloxicam is a non-steroidal anti-inflammatory drug (NSAID) often used in humans and companion animals to treat arthritis, having strong anti-inflammatory and fever-reducing properties. The objectives of this study were to evaluate the effects of a new compounded oral drench suspension formulation of Meloxicam on sow body temperature in the first 24 hours after farrowing, piglet survivability, and piglet growth. A total of 851 sows in a commercial farm were randomly assigned to receive a single, 90 mg dose (6 mL of a 1.5% suspension) of Meloxicam via oral drench at completion of farrowing (MEL, n = 428) or receive no drug after farrowing (CON, n = 423). Rectal temperatures were taken at the end of farrowing, and 12 and 24 hours after farrowing to monitor sow body temperatures. As standard practice on this farm, sows with a temperature ≥ 39.7 °C at 24 hours post-farrowing were treated with flunixin (NSAID) and ampicillin injectables for 3 consecutive days (MEDS). Litter size and weights were recorded on day 0 and again on the day before weaning. Piglet deaths and reasons were recorded daily to determine piglet survivability and the body weights of dead piglets were recorded. The Mixed procedure of SAS 9.4 (Cary, North Carolina) was used to analyze the interaction between treatment (MEL or CON) and parity (P1 vs. P2 and P3 vs. P&amp;gt;3) as the main effects. A 2x2 factorial design was used to reanalyze the interaction of Meloxicam treatment with additional medicated pigs (MEDS) using PROC Mixed in SAS with MEL and MEDS as main effects, and litter birthweight quartile and number nursed covariates where appropriate. MEL was successful in reducing the temperature of sows by 0.16 °C in the first 12 hours after farrowing (P = 0.0013). For all groups, sows greater than parity 3 had lower temperatures in the first 24 hours after farrowing (P = 0.0083). Gilts in the MEL group required less additional medication than gilts in the CON group (P = 0.0102). Treating sows with Meloxicam tended to reduce the incidence of scours in piglets (P = 0.0907). MEL did not significantly (P &amp;gt; 0.05) impact preweaning mortality (CON = 12.9%, MEL = 12.3%), piglet weaning weight (CON: 5.4 kg ± 0.10; MEL: 5.5 kg ± 0.04), and no differences were observed between piglet weight and age at death between the treatment groups. This study exhibits the ability of a single dose of Meloxicam at farrowing to reduce fever within the first 12 hours of dosing and its potential to reduce the incidence of scours in piglets. Future studies investigating a longer Meloxicam therapy period post-farrowing will give insight into the use of Meloxicam as a fever-reducer to improve sow and piglet lactation performance and survivability.

Evaluation of histologic, antiapoptotic and antioxidant effects of melatonin against the acute ocular toxicity of Cisplatin

This study aimed to investigate the protective effect of melatonin against the acute toxicity of cisplatin in ocular tissues. The eyes of 40 rats were divided into 4 groups: Control group (10 rats), Melatonin (Mel) group (10 rats), Cisplatin (Cis) group (10 rats), Melatonin (Mel) + Cisplatin (Cis) group (10 rats). Retina, cornea, and ciliary body tissues were examined after hematoxylin-eosin staining of sections obtained from the eyes and were scored for disorganization and degeneration. Apoptotic cells were counted for the retina, cornea, and ciliary body with the TUNEL (Terminal deoxynucleotidyl transferase dUTP nick end labeling) method. The total antioxidant status (TAS) / total oxidant status (TOS) of homogenized eye tissues were measured. While apoptotic cells were found to increase in the cornea of the Cisplatin (Cis) group, no difference was found regarding the retina and ciliary body cell count. An increased number of apoptotic cells in the cornea of the Cis group was found while there was a decrease in the group where Cisplatin and Melatonin were administered together (Mel+Cis group). There was no statistically significant difference amongst groups for TOS or TAS. Melatonin had a partial protective effect against histological damage.

Role of Txnrd3 in NiCl2-induced kidney cell apoptosis in mice: Potential therapeutic effect of melatonin

Nickel (Ni) exposure is a significant risk factor for kidney dysfunction and oxidative stress injury in humans. Thioredoxin reductase 3 (Txnrd3), an important enzyme in animals, plays a role in maintaining cellular homeostasis and regulating oxidative stress. However, its protective effect against kidney injury has been determined. Melatonin (Mel) has antioxidant and anti-apoptotic effects and therefore may be a preventive and therapeutic agent for kidney injury. Our study aimed to investigate the roles of Mel and Txnrd3 in the treatment of nickel-induced renal injury. We divided 80 wild-type mice and 80 Txnrd3 -/- mice (C57BL/6 N) into a control group treated with saline, Ni group treated with 10 mg/kg NiCl2, Mel group treated with 2 mg/kg Mel, and Ni + Mel group given NiCl2 and Mel for 21 days. Histopathological and ultrastructural observation of the kidney showed that nuclei were wrinkled and mitochondrial cristae were broken in the Ni group, and these changes were significantly attenuated by Mel treatment. Mitochondrial and nuclear damage improved significantly in the Ni + Mel and Txnrd3-/- Ni + Mel groups. Furthermore, NiCl2 exposure decreased T-AOC, SOD, and GSH activities in the kidney. The decreases in antioxidant enzyme activity were attenuated by Mel, and these improvements were abolished by Txnrd3 knockout. NiCl2-induced increases in the mRNA and protein levels of apoptosis factors (Bax, Cyt-c, caspase-3, and caspase-9) were attenuated by Mel treatment, and Txnrd3 knockout abolished the repressive effect of Mel on apoptosis genes. Overall, we concluded that Mel improves oxidative stress and apoptosis induced by NiCl2 by regulating Txnrd3 expression in the kidney. Our results provide evidence for the role of Mel in NiCl2-induced kidney injury and identify Txnrd3 as a potential therapeutic target for renal injury.

Melatonin and chronic ethanol consumption: effects on the offspring liver and kidney

The aim of this research was to assess whether the administration of melatonin during pregnancy and lactation can mitigate alcohol-induced liver and kidney damage in the offspring. Three groups were formed with the offspring of 30 albino Wistar rats from the UFRPE bioterium: control group – Offspring of rats that did not consume alcohol; alcohol group – Offspring of rats that consumed alcohol; alcohol+mel group – Offspring of rats that consumed alcohol and received melatonin. The female rats received 3 g/Kg of alcohol and 0.8 mg/Kg of melatonin during the gestational and lactation period. The rat pups were euthanized at 30 days of age. The collected organs underwent histological procedures for morphometric, histopathological and statistical analyses. In the liver of the alcohol group, congestion in the portal and centrolobular veins, steatosis, and alterations in the sizes of hepatic parenchyma were observed, which were not present in the alcohol+mel and control groups. In the alcohol group, the kidneys also showed congestion in the cortical area, without the subcapsular space and with altered glomerulus size, on the other hand, the group treated with melatonin did not present alterations in these organs. The statistical analyses of the weights and lengths of the alcohol+mel group also did not reveal any significant alterations when compared to the group exposed only to alcohol. Thus, melatonin acted positively, interfering and mitigating the harmful effects that ethanol had on the liver, kidneys, weight and length of offspring whose mothers were subjected to chronic alcohol consumption.

Melatonin associated with a high-fat diet during pregnancy and lactation prevents liver changes in the offspring

In the present study, we set out to determine whether melatonin combined with a high-fat diet during pregnancy and lactation can prevent liver disorders in offspring. Forty rats were divided into four groups: DC - pregnant rats submitted to the standard diet; DC + Mel - pregnant rats submitted to the standard diet combined with melatonin; HFD - pregnant rats submitted to a high-fat diet; HFD + Mel - pregnant rats submitted to a high-fat diet combined with melatonin. Morphophysiological and biochemical parameters were analyzed. Melatonin (5 mg/kg) was administered intraperitoneally. The HFD group offspring showed an increase in AST, ALT, alkaline phosphatase, cholesterol, triglycerides, LDL and glucose levels, and a reduction in HDL and lipase levels. In the liver obseved steatosis, hepatocellular ballooning, increased lobular parenchyma and reduced non-lobular parenchyma, beside reduced liver glycogen and fibrosis. These changes were not observed in the HFD + Mel group. In conclusion, melatonin combined with a high-fat diet preserves the liver architecture and function in the offspring.

Robenacoxib versus meloxicam following ovariohysterectomy in cats: A randomised, prospective clinical trial involving owner-based assessment of pain.

Injectable non-steroidal anti-inflammatory drugs (NSAIDs) are commonly prescribed to queens undergoing ovariohysterectomy (OVH), but the requirement for postoperative administration is unclear and practices vary. Existing studies assessing efficacy rely on pain scoring by experienced clinicians. However, following OVH, most cats are discharged within hours of recovery. Cats undergoing OVH were randomly assigned to two treatment groups: MEL and ROB. Cats in the MEL group (n = 76) received meloxicam (0.2mg/kg) and those in the ROB group (n = 65) received robenacoxib (2mg/kg). Owners were contacted by a blinded assessor 3 days postoperatively and asked to identify physical or behavioural changes and to assign pain scores using a numerical rating scale. More cats in theROB group displayed abnormal behaviours than cats in the MEL group (p = 0.03). Most owners assigned a pain score of 0 (72%) (n = 101), but pain scores were significantly higher in the ROB group than in the MEL group (p = 0.005). Methods of owner assessment of pain in cats have not been validated. Both meloxicam and robenacoxib are effective in controlling postoperative pain. Meloxicam may have improved efficacy in certain patient populations. Applying a blanket approach to prescribing NSAIDs to cats undergoing OVH postoperatively may not be necessary. This has safety, environmental and cost implications.

Maternal melatonin supplementation shapes gut microbiota and protects against inflammation in early life

BackgroundGut microbiota colonization is critical for immune education and nutrient metabolism. Research shows that melatonin has beneficial effects as a therapy for many diseases via modulating gut dysbiosis. However, it is unclear whether melatonin alters gut microbiota colonization in early life. MethodsIn the experimental group (Mel), mice were intraperitoneally injected with melatonin at 10 mg/kg body weight for embryonic days 14–16 and received drinking water containing 0.4 mg/mL melatonin until 28 days postpartum. In the control group (Ctrl), mice were injected with the same volume of 2.5% ethanol in saline and provided with standard water. Two more groups were created by treating neonatal mice with 20 mg/kg lipopolysaccharide (LPS) to induce inflammation, resulting in the groups Ctrl + LPS and Mel + LPS, respectively. We examined the gut microbiota of the neonatal mice in the Ctrl and Mel group on Days 7, 14, 21, and 28 post-birth. On Day 14, melatonin and short-chain fatty acids (SCFAs) concentrations were measured in the Ctrl and Mel group and the mice were treated with LPS to be evaluated for intestinal injury and inflammatory response 15 h post treatment. According to the result of the SCFAs concentrations, some neonatal mice were intraperitoneally injected with 500 mg/kg sodium butyrate (SB) from Days 11–13, intraperitoneally injected with 20 mg/kg LPS on Day 14, and then euthanized by carbon dioxide inhalation the next morning. Intestinal injury and inflammatory responses were evaluated in the Ctrl + LPS and SB + LPS groups, respectively. ResultsBy Day 14, it was evident that maternal melatonin supplementation significantly increased the relative abundance of Firmicutes in the ileal [61.03 (35.35 – 76.18) % vs. 98.02 (86.61 – 99.01) %, P = 0.003] and colonic [73.88 (69.77 – 85.99) % vs. 96.16 (94.57 – 96.34) %, P = 0.04] microbiota, the concentration of melatonin (0.79 ± 0.49 ng/ml vs. 6.11 ± 3.48 ng/ml, P = 0.008) in the gut lumen, and the fecal butyric acid (12.91 ± 5.74 μg/g vs. 23.58 ± 10.71 μg/g, P = 0.026) concentration of neonatal mice. Melatonin supplementation, and sodium butyrate treatment markedly alleviated intestinal injury and decreased inflammatory factors in neonatal mice. ConclusionThis study suggests that maternal melatonin supplementation can shape the gut microbiota and metabolism of offspring under normal physiological conditions and protect them against LPS-induced inflammation in early life.

Randomised Control Trial Investigating the Efficacy of Meloxicam and Sodium Salicylate Non-Steroidal Anti-Inflammatory Drugs for Calf Cautery Disbudding.

Disbudding calves using hot iron cautery is a routine management procedure to destroy the germinal cells around the horn bud in calves. It is recommended that NSAIDs are used in conjunction with local anaesthesia to reduce pain in calves during and after the procedure. In this study, two treatment groups were examined; calves in the positive control MEL group received subcutaneous meloxicam, and SAL calves received sodium salicylate orally for three days, both in addition to a local anaesthesia. Tri-axis accelerometers were attached to the calves, and DLWG (Daily Live Weight Gain) was measured. There was no significant difference between the treatment groups with regard to DLWG (p = 0.52), MI (motion index (p = 0.66)), lying bouts (p = 0.96) or lying times (p = 0.54). Given these findings, sodium salicylate may offer a lower-cost option for farmers when given at licensed doses compared to meloxicam, as well as providing a reduced-stress method of NSAID administration via an oral route. In addition, this study identified significant differences in activity in the time periods before and after disbudding, with MI (p < 0.01), lying bouts (p = 0.002) and lying times (p < 0.001) indicating changes in behaviour which extended to five days post disbudding.

35 Effects of melatonin on inflammatory marker serum amyloid A in horses after exercise

Performance horses are regularly exposed to various stressors, such as training and exercise, that negatively impact their performance which may lead to increased oxidative stress (OS) and inflammation. Although important for the adaptive response, prolonged and unresolved OS and inflammation may decrease athletic performance or cause unnecessary cellular damage. Dietary supplements, such as antioxidants, have been shown to mitigate the negative effects of OS and inflammation and therefore may enhance performance. One such antioxidant that has been of interest is melatonin. The objectives of this study were to evaluate the potential of melatonin to reduce Serum Amyloid A (SAA), a sensitive inflammatory marker, in horses after exercise. Horses (n = 6) were randomly assigned to 2 groups (CON; n = 3, no supplement or MEL; n = 3, 20 g melatonin). Horses received diet based on BW (1% BW Nutrena Impact 12% Pellets and 2% BW bermudagrass hay/d). A switchback design was used, with 2 experimental trial periods lasting 14-d with a 30-d washout period in-between. Supplementation was given orally on exercise days during each trial period. Horses underwent 1.5hr of moderate-intensity exercise (avg >90 BPM), at 0700 3 d/wk. Blood was drawn before exercise (PRE), and at 30- and 90-min post-exercise. On exercise days (ED), horses received supplementation after PRE blood draw and before exercise (0630).After the washout period, the treatment groups were swapped, and the study was repeated, resulting in 12 ED total. Blood was collected via jugular venipuncture, immediately processed to separate plasma, and stored for analysis. SAA ELISA kits (Thermo Fisher Scientific Inc., Massachusetts) were used to determine blood SAA concentration. The first and last ED of each trial period were analyzed (ED1/ED6/ED7/ED12), and interactions of treatment, time, and day were analyzed with significance set at (P ≤ 0.05). PRE ED1 and 7 were set as baseline values, with no significant differences in baseline levels between treatments (P > 0.1862). There was a significant difference between treatments at 30- (P ≤ 0.01) and 90-min (P ≤ 0.01) post-exercise on ED1, 7, and 12, with average plasma SAA concentrations being lower for MEL group at all time points. There was also a treatment*day interaction for ED1 (P = 0.0005), ED7 (P = 0.0218), and ED12 (P = 0.0001), with MEL having lower SAA blood concentrations as compared with CON. Lower concentrations of SAA in MEL horses suggest melatonin supplementation may reduce inflammatory blood markers and, in turn, may suggest lower levels of inflammation in horses after exercise.

Melatonin alleviates ovarian function damage and oxidative stress induced by dexamethasone in the laying hens through FOXO1 signaling pathway

Oxidative stress can trigger follicular atresia, and decrease follicles quantity in each development stage, thereby alleviating reproductive activity. The induction of oxidative stress in chickens through intraperitoneal injection of dexamethasone is a reliable and stable method. Melatonin has been shown to mitigate oxidative stress in this model, but the underlying mechanism remains unclear. Therefore, this study aimed to investigate whether melatonin can recover aberrant antioxidant status induced by dexamethasone and the specific mechanism behind melatonin-dependent protection. A total of 150 healthy 40-wk-old Dawu Jinfeng laying hens with similar body weights and laying rates were randomly divided into three groups, with five replicates per group and 10 hens per replicate. The hens in the control group (NS) received intraperitoneal injections of normal saline for 30 d, the dexamethasone group (Dex+NS) received 20 mg/kg dose of dexamethasone for the first 15 d, followed by the 15 d of normal saline treatment. While in the melatonin group (Dex+Mel), dexamethasone (20 mg/kg dose) was injected intraperitoneally in the first 15 d, and melatonin (20 mg/kg/d) was injected in the last 15 d. The results showed that dexamethasone treatment significantly enhanced oxidative stress (P < 0.05), while melatonin not only inhibited the oxidative stress but also notably enhanced the antioxidant enzymes superoxide dismutase (SOD), catalase activity (CAT), glutathione peroxidase (GSH-Px), and antioxidant genes CAT, superoxide dismutase 1 (SOD1), glutathione peroxidase 3 (GPX3), and recombinant peroxiredoxin 3(PRDX3) expression (P < 0.05). Melatonin treatment also markedly reduced 8-hydroxy deoxyguanosine(8-OHdG), malondialdehyde (MDA), and reactive oxygen species (ROS) levels (P < 0.05) and apoptotic genes Caspase-3, Bim, and Bax in the follicle. In the Dex+Mel group, the Bcl-2 and SOD1 protein levels were also increased (P < 0.05). Melatonin inhibited the forkhead Box Protein O1(FOXO1) gene and its protein expression (P < 0.05). In general, this investigation revealed that melatonin might decrease oxidative stress and ROS by enhancing antioxidant enzymes and genes, activating the antiapoptotic genes, and inhibiting the FOXO1 pathway in laying hens.

Melatonin pretreatment can improve the therapeutic effect of adipose-derived stem cells on CCl4-induced liver fibrosis

In this study, the therapeutic effect of Mel-incubated Adipose-derived mesenchymal stem cells (ADSCs) on CCl4-induced hepatic fibrosis was investigated. Mice with hepatic fibrosis were intraperitoneally injected with 8% CCl4 twice a week for 4 weeks. Starting from week 5, mice in the ADSC group and ADSC + Mel group were injected with 1 mL PBS cell suspension containing 1 × 106 ADSCs or ADSCs pretreated with 50 nM Mel twice a week for 2 consecutive weeks. Results: In the model group, severe histopathological changes were observed in the liver, including severe vacuolation, nuclear fragmentation, and liver fibrosis, and these changes were ameliorated by Mel-pretreated ADSCs. RT-qPCR results showed that Mel-induced ADSCs significantly inhibited the expression of proapoptotic genes (Caspase-8, Bax, and Caspase-3) and promoted the expression of an anti-apoptotic gene (Bcl-2). Immunohistochemical results showed that a large number of MMP-9-, TGF-β-, and MMP-2-positive cells were present in the liver tissues of the model group, while the number of positive cells was reduced by Mel-induced ADSCs. ELISA results showed that the ADSC pretreated with Mel also significantly reduced the expression levels of TNF-α and IL-6. Conclusion: ADSCs pretreated with Mel significantly improved CCl4-induced liver fibrosis.