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Journal of Medical Imaging and... Jun 2024The purpose of this study was to determine patient perceptions of an advanced practice radiation therapist (APRT) prescribing medication for radiation therapy...
INTRODUCTION
The purpose of this study was to determine patient perceptions of an advanced practice radiation therapist (APRT) prescribing medication for radiation therapy treatment-related side effects. By comprehending patient perceptions, it is important to implement change in order to improve patients' quality of life.
METHODS
A literature review was conducted on advanced practice (AP) roles in Canada and world-wide; the roles searched were: APRT, nurse practitioner and pharmacist. The search focused on evidence demonstrating improvements made to patient care due to the implementation of these roles. Based on this review and input from a team of experts a qualitative semi-structured interview survey was designed, and pilot tested. The survey consisted of five open-ended questions, which were designed to determine patient satisfaction of an APRT prescribing medication over the course of their radiation therapy treatments. Patients undergoing head and neck radiation therapy treatments at a large, academic cancer centre were invited to participate. Six patients who had a head and neck APRT involved in their treatment were interviewed. A comprehensive thematic analysis was then conducted using the transcripts created from these interviews, which was followed by two independent blinded analyses to ensure validity of the results.
DISCUSSION
The thematic analysis produced four salient themes which were: side effect management, care provided by the APRT in comparison to other healthcare workers, patients' access to care, and overall patient satisfaction. Common medications for head and neck radiation therapy treatment related side effects were discussed and these were: Magic Mouthwash, Xylocaine, Nystatin, Benadryl, Advil, Tylenol, Dexamethasone, Tantum, Biotene, Mucaine, Flamazine, Hydrocortisone, Ondansetron, Senokot, and narcotics.
CONCLUSION
This study was valuable to understand patient experiences and provide evidence to change processes in order to improve quality of patient centered care. The study revealed that although patients were happy with the process of prescribing medication, they all agreed that having an advanced practice radiation therapist prescribe would improve care. Patient responses further demonstrated the need for future research in regards to side effect management as a whole by APRTs as well as how role clarification can impact patient perceptions of APRTs.
PubMed: 38878617
DOI: 10.1016/j.jmir.2024.101443 -
Paediatric Drugs Jul 2024Pediatric obsessive-compulsive disorder (OCD) is a chronic, potentially debilitating psychiatric condition. Although effective treatments exist, at least 10% of youth do... (Review)
Review
Pediatric obsessive-compulsive disorder (OCD) is a chronic, potentially debilitating psychiatric condition. Although effective treatments exist, at least 10% of youth do not achieve remission despite receiving first-line treatments. This article reviews the extant, albeit limited, evidence supporting treatment approaches for youth with treatment-resistant OCD. A literature search for articles addressing pediatric treatment-resistant OCD was conducted through April 11, 2024. These results were augmented by searching for treatment-resistant OCD in adults; treatment strategies discovered for the adult population were then searched in the context of children and adolescents. In general, intensive treatment programs and antipsychotic augmentation of an antidepressant had the most substantial and consistent evidence base for treatment-resistant youth with OCD, although studies were limited and of relatively poor methodological quality (i.e., open trials, naturalistic studies). Several pharmacological approaches (clomipramine, antipsychotics [e.g., aripiprazole, risperidone], riluzole, ketamine, D-cycloserine, memantine, topiramate, N-acetylcysteine, ondansetron), largely based on supporting data among adults, have received varying levels of investigation and support. There is nascent support for how to treat pediatric treatment-resistant OCD. Future treatment studies need to consider how to manage the significant minority of youth who fail to benefit from first-line treatment approaches.
Topics: Humans; Obsessive-Compulsive Disorder; Child; Antipsychotic Agents; Adolescent; Antidepressive Agents
PubMed: 38877303
DOI: 10.1007/s40272-024-00639-5 -
European Journal of Internal Medicine Jun 2024Alcohol use disorder (AUD) is among the leading causes of morbidity and mortality worldwide, and over 95 million people live with alcohol dependence globally. The...
BACKGROUND
Alcohol use disorder (AUD) is among the leading causes of morbidity and mortality worldwide, and over 95 million people live with alcohol dependence globally. The estimated heritability of AUD is 50-60 %, and multiple genes are thought to contribute to various endophenotypes of the disease. Previous clinical trials support a precision medicine approach using ondansetron (AD04, a 5-HT3 antagonist) by segregating AUD populations by the bio-genetic endophenotype of specific serotonergic genotypes and the bio-psychosocial endophenotype of the severity of drinking or both. By targeting the modulation of biogenetic signaling within the biopsychosocial context of AUD, low-dose AD04 holds promise in reducing alcohol consumption among affected individuals while minimizing adverse effects.
METHODS
This was a phase III, 6-month, 25-site, randomized, placebo-controlled clinical trial using AD04 to treat DSM-V-categorized AUD individuals who were pre-stratified into the endophenotypes of heavy or very heavy drinking individuals and possessed a pre-defined profile of genetic variants related to the serotonin transporter and serotonin-3AB receptor. Participants (N = 303) presented moderate to severe AUD, >80 % were men, mostly in their fifties, and >95 % were of European descent. Low-dose AD04 (approx. 033 mg twice daily) or a matching placebo was administered twice daily for 6 months. Brief Behavioral Compliance Enhancement Treatment (BBCET [53]) was administered every two weeks to enhance medication compliance and clinic attendance.
RESULTS
There was a significant reduction in the monthly percentage of heavy drinking days, PHDD (-46·7 % (2·7 %), 95 %CI: -52·1 % to -41·2 % vs. -38·1 % (2·9 %), 95 %CI: -43·8 % to -32·5 %, respectively; LS mean difference=-8·5 %; p = 0.03) among AD04-treated vs. placebo-receiving heavy drinking individuals at month 6. Heavy drinking individuals were also less likely to be diagnosed with AUD [Month 1: -32·0 % (2·8 %), 95 %CI: -37·5 % to -26·5 % vs. -23·2 % (2·9 %), 95 %CI: -28·9 to -17·5 %; LS mean difference= -8·8 %; p = 0·026)], and improved on the WHO quality of life BREF scale with a significant effect for at least a 1-level downward shift (OR = 3.4; 95 % CI: 1·03-11·45, p = 0·044). Importantly, heavy drinking individuals, as distinct from very heavy drinking individuals, were the bio-psychosocial endophenotype more predictive of therapeutic response to AD04. AD04 had an exceptional safety and tolerability profile, like the placebo's.
CONCLUSIONS
In this Phase 3 clinical trial, AD04 was shown to be a promising treatment for currently drinking heavy drinking individuals with AUD who also possess a specific genotypic profile in the serotonin transporter and serotonin-3AB receptor complex. Using AD04 to reduce the harm of AUD in heavy drinking individuals who are currently drinking, without the necessity of abstinence or detoxification from alcohol use, is an important advance in the field of precision medicine. AD04's adverse events profile, which was like placebo, should enhance accessibility and acceptance of modern medical treatment for AUD by lowering the incorrect but commonly perceived stigma of personal failure.
PubMed: 38876929
DOI: 10.1016/j.ejim.2024.06.001 -
Minerva Anestesiologica Jun 2024Major spine surgery is associated with severe postoperative pain and increased opioid consumption. Opioid-free anesthesia (OFA) is thought to provide adequate... (Randomized Controlled Trial)
Randomized Controlled Trial Comparative Study
BACKGROUND
Major spine surgery is associated with severe postoperative pain and increased opioid consumption. Opioid-free anesthesia (OFA) is thought to provide adequate intraoperative analgesia with reduced postoperative opioid consumption. The aim of this study is to compare the impact of intraoperative OFA approach to the conventional opioid-based anesthesia (OBA) on postoperative pain, opioid consumption, and related side effects in patients undergoing multilevel spinal fusion surgery.
METHODS
Forty-eight patients undergoing elective major spine surgery were randomly allocated to either receive intraoperative dexmedetomidine and lidocaine (OFA group) or fentanyl during induction and intraoperative remifentanil (OBA group). All patients received intraoperative sevoflurane, propofol, rocuronium, ketamine, dexamethasone, ondansetron and postoperative paracetamol and patient-controlled analgesia device set to deliver intravenous morphine for 48 hours after surgery. Postoperative pain was measured using numerical rating scale. Opioid side effects were documented, when present.
RESULTS
OFA group required less morphine in the first 24 hours post-surgery (17.28±12.25 mg versus 27.96±19.75 mg, P<0.05). The incidence of postoperative nausea and vomiting (PONV) was significantly lower in the OFA group. More patients in the OFA group required antihypertensive medications compared to patients in the OBA group (P<0.05). In the post anesthesia care unit, OFA patients had a significantly longer stay than OBA patients (114.1±49.33 min versus 89.96±30.71 min, P<0.05).
CONCLUSIONS
OFA can be an alternative to OBA in patients undergoing multilevel spine fusion surgery. OFA reduces opioids consumption in the first 24 hours and PONV.
Topics: Humans; Male; Female; Analgesics, Opioid; Middle Aged; Prospective Studies; Pain, Postoperative; Adult; Spine; Dexmedetomidine; Aged; Spinal Fusion; Postoperative Nausea and Vomiting; Remifentanil; Anesthesia
PubMed: 38869262
DOI: 10.23736/S0375-9393.24.17962-X -
Journal of Pharmacological and... Jun 2024Nonclinical evaluation of the cardiovascular effects of novel chemical or biological entities (NCE, NBEs) is crucial for supporting first-in-human clinical trials. One...
INTRODUCTION
Nonclinical evaluation of the cardiovascular effects of novel chemical or biological entities (NCE, NBEs) is crucial for supporting first-in-human clinical trials. One important aspect of these evaluations is the assessment of potential QT/QTc prolongation risk, as drug-induced QT prolongation can have catastrophic effects. The recent publication of E14/S7B Q&As allows for the situational incorporation of nonclinical QTc data as part of an integrated risk assessment for a Thorough QT (TQT) waiver application provided certain best practice criteria are met. Recent publications provided detailed characterization of nonclinical QTc telemetry data collected from the commonly used Latin square study design.
METHODS
To understand whether data from alternate telemetry study designs were sufficient to serve as part of the E14/S7B integrated risk assessment, we report the performance and translational sensitivity to identify clinical risk of QTc prolongation risk for an ascending dose telemetry design.
RESULTS
The data demonstrated low variability in QTci interval within animals from day to day, indicating a well-controlled study environment and limited concern for uncontrolled effects across dosing days. Historical study variances of the ascending dose design with n = 4 subjects, measured by least significant difference (LSD) and root mean square error (RMSE) values, were low enough to detect a + 10 ms QTci interval change, and the median minimum detectable difference (MDD) for QTci interval changes was <10 ms. Furthermore, concentration-QTci (C-QTci) assessments to determine +10 ms QTci increases for known hERG inhibitors were comparable to clinical CC values listed in the E14/S7B training materials, supporting the use of the ascending dose design in an E14/S7B integrated risk assessment.
DISCUSSION
These findings suggest that the ascending dose design can be a valuable tool in nonclinical evaluation of QT/QTc prolongation risk and the support of TQT waiver applications.
PubMed: 38851600
DOI: 10.1016/j.vascn.2024.107525 -
Annals of Medicine and Surgery (2012) Jun 2024Spinal anesthesia is commonly performed for cesarean section, however, postdural puncture headache (PDPH) is one of its most common adverse effects. Ondansetron is an...
BACKGROUND
Spinal anesthesia is commonly performed for cesarean section, however, postdural puncture headache (PDPH) is one of its most common adverse effects. Ondansetron is an antiemetic for cancer treatment and analgesia-induced nausea and vomiting. In this study, the authors aim to evaluate the effect of postoperative ondansetron on PDPH.
METHODS
In this randomized controlled clinical trial study, 120 pregnant patients are ASA ll, undergoing elective cesarean section, were randomized into two groups (placebo or study). The patients in the study group, immediately after the birth of a baby and 24 h after the operation, received ondansetron 4 mg IV while the placebo group received a placebo. The severity and incidence of headache, postoperative nausea and vomiting, dizziness, neck and lower back pain, and the use of analgesia was assessed in the two groups.
RESULTS
The significant meaning of the time effect (<0.001) indicated that regardless of the group, for each unit increase in time, the chance of developing a headache increased by 23%, which was statistically significant. Also, the significant meaning of the group effect indicated that regardless of time, patients who did not take indomethacin had ~4.11 times higher chances of developing a headache compared to those who received the medication, which was statistically significant (=0.004).
CONCLUSION
The administration of ondansetron significantly reduces the occurrence of postspinal anesthesia headaches and neck pain. There was no significant difference in headache severity between the two study groups.
PubMed: 38846852
DOI: 10.1097/MS9.0000000000002081 -
Journal of Parasitic Diseases :... Jun 2024A 3-year-old male rhesus macaque was presented at Referral Veterinary Polyclinic-Teaching Veterinary Clinical Complex, with a chief complaint of chronic diarrhoea and...
A 3-year-old male rhesus macaque was presented at Referral Veterinary Polyclinic-Teaching Veterinary Clinical Complex, with a chief complaint of chronic diarrhoea and swelling of dependent body parts. The patient's history indicates that the monkey had been experiencing diarrhoea for the past month, with 2-3 episodes of vomiting in the last 2 days. Additionally, oedema has developed within the last 2 weeks. The clinical examination findings revealed dullness and depression, the mucus membrane appeared pale, with a temperature-102.1 °F, a respiration rate-28/min, and a heart rate-92/min. The capillary refill time was 4 s. During the physical examination, the animal exhibited oedema on the dependent part of the body and faecal staining around the perineum along with loose yellow stool. Direct saline and iodine mount faecal smear examination revealed the presence of many motile pear-shaped flagellated protozoa and round vacuolated organisms. Giemsa-stained faecal smear cytology confirmed the presence of sp. and sp. along with many microbes. The faecal culture was negative for all pathogenic microbes. The case was diagnosed as co-infection Blastocystosis and intestinal trichomoniasis. The treatment was initiated with a combination of sulfamethoxazole + trimethoprim @ 35 mg/kg body weight and metronidazole @25 mg/kg administered orally once daily for 7 days. Supportive therapy includes hematinic injection (iron sorbitol, folic acid and vitamin B12) @ 1 ml total dose, administered intramuscularly on alternate days for four occasions as well as intravenous infusion of crystalline amino acid @ 5 ml total dose on alternate days for four occasions. To manage vomition, injection ondansetron was [email protected] mg/kg intramuscularly, twice daily for 3 days and H2 blockers, including injection ranitidine@2 mg/kg intramuscularly twice daily for 3 days. Electrolyte and probiotic supplementation were administered orally. After 7 days of therapy, the oedema had significantly improved and episodes of vomition were stopped but there was no significant improvement in the episode of diarrhoea and consistency of faeces. Unfortunately, on the 10th day of therapy, the animal suddenly collapsed. Understanding the virulence pattern of opportunistic protozoa in primates is crucial, and identifying suitable therapeutic candidates to prevent fatal outcomes is the need of the hour, especially considering protozoal infections as an important differential diagnosis in gastrointestinal tract-related ailments. Our study successfully demonstrated the co-occurrence of blastocystosis and intestinal trichomoniasis, both uncommon infections with potential zoonotic implications.
PubMed: 38840877
DOI: 10.1007/s12639-024-01659-1 -
The Cochrane Database of Systematic... Jun 2024Postburn pruritus (itch) is a common and distressing symptom experienced on healing or healed burn or donor site wounds. Topical, systemic, and physical treatments are... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Postburn pruritus (itch) is a common and distressing symptom experienced on healing or healed burn or donor site wounds. Topical, systemic, and physical treatments are available to control postburn pruritus; however, it remains unclear how effective these are.
OBJECTIVES
To assess the effects of interventions for treating postburn pruritus in any care setting.
SEARCH METHODS
In September 2022, we searched the Cochrane Wounds Specialised Register, the Cochrane Central Register of Controlled Trials (CENTRAL), Ovid MEDLINE (including In-Process & Other Non-Indexed Citations), Ovid Embase, and EBSCO CINAHL Plus. We also searched clinical trials registries and scanned references of relevant publications to identify eligible trials. There were no restrictions with respect to language, publication date, or study setting.
SELECTION CRITERIA
Randomised controlled trials (RCTs) that enrolled people with postburn pruritus to compare an intervention for postburn pruritus with any other intervention, placebo or sham intervention, or no intervention.
DATA COLLECTION AND ANALYSIS
We used the standard methodological procedures expected by Cochrane. We used GRADE to assess the certainty of the evidence.
MAIN RESULTS
We included 25 RCTs assessing 21 interventions with 1166 randomised participants. These 21 interventions can be grouped into six categories: neuromodulatory agents (such as doxepin, gabapentin, pregabalin, ondansetron), topical therapies (such as CQ-01 hydrogel, silicone gel, enalapril ointment, Provase moisturiser, beeswax and herbal oil cream), physical modalities (such as massage therapy, therapeutic touch, extracorporeal shock wave therapy, enhanced education about silicone gel sheeting), laser scar revision (pulsed dye laser, pulsed high-intensity laser, fractional CO2 laser), electrical stimulation (transcutaneous electrical nerve stimulation, transcranial direct current stimulation), and other therapies (cetirizine/cimetidine combination, lemon balm tea). Most RCTs were conducted at academic hospitals and were at a high risk of performance, attrition, and detection bias. While 24 out of 25 included studies reported change in burn-related pruritus, secondary outcomes such as cost-effectiveness, pain, patient perception, wound healing, and participant health-related quality of life were not reported or were reported incompletely. Neuromodulatory agents versus antihistamines or placebo There is low-certainty evidence that doxepin cream may reduce burn-related pruritus compared with oral antihistamine (mean difference (MD) -2.60 on a 0 to 10 visual analogue scale (VAS), 95% confidence interval (CI) -3.79 to -1.42; 2 studies, 49 participants). A change of 2 points represents a minimal clinically important difference (MCID). Due to very low-certainty evidence, it is uncertain whether doxepin cream impacts the incidence of somnolence as an adverse event compared to oral antihistamine (risk ratio (RR) 0.64, 95% CI 0.32 to 1.25; 1 study, 24 participants). No data were reported on pain in the included study. There is low-certainty evidence that gabapentin may reduce burn-related pruritus compared with cetirizine (MD -2.40 VAS, 95% CI -4.14 to -0.66; 1 study, 40 participants). A change of 2 points represents a MCID. There is low-certainty evidence that gabapentin reduces the incidence of somnolence compared to cetirizine (RR 0.02, 95% CI 0.00 to 0.38; 1 study, 40 participants). No data were reported on pain in the included study. There is low-certainty evidence that pregabalin may result in a reduction in burn-related pruritus intensity compared with cetirizine with pheniramine maleate (MD -0.80 VAS, 95% CI -1.24 to -0.36; 1 study, 40 participants). A change of 2 points represents a MCID. There is low-certainty evidence that pregabalin reduces the incidence of somnolence compared to cetirizine (RR 0.04, 95% CI 0.00 to 0.69; 1 study, 40 participants). No data were reported on pain in the included study. There is moderate-certainty evidence that ondansetron probably results in a reduction in burn-related pruritus intensity compared with diphenhydramine (MD -0.76 on a 0 to 10 numeric analogue scale (NAS), 95% CI -1.50 to -0.02; 1 study, 38 participants). A change of 2 points represents a MCID. No data were reported on pain and adverse events in the included study. Topical therapies versus relevant comparators There is moderate-certainty evidence that enalapril ointment probably decreases mean burn-related pruritus compared with placebo control (MD -0.70 on a 0 to 4 scoring table for itching, 95% CI -1.04 to -0.36; 1 study, 60 participants). No data were reported on pain and adverse events in the included study. Physical modalities versus relevant comparators Compared with standard care, there is low-certainty evidence that massage may reduce burn-related pruritus (standardised mean difference (SMD) -0.86, 95% CI -1.45 to -0.27; 2 studies, 166 participants) and pain (SMD -1.32, 95% CI -1.66 to -0.98). These SMDs equate to a 4.60-point reduction in pruritus and a 3.74-point reduction in pain on a 10-point VAS. A change of 2 VAS points in itch represents a MCID. No data were reported on adverse events in the included studies. There is low-certainty evidence that extracorporeal shock wave therapy (ESWT) may reduce burn-related pruritus compared with sham stimulation (SMD -1.20, 95% CI -1.65 to -0.75; 2 studies, 91 participants). This equates to a 5.93-point reduction in pruritus on a 22-point 12-item Pruritus Severity Scale. There is low-certainty evidence that ESWT may reduce pain compared with sham stimulation (MD 2.96 on a 0 to 25 pressure pain threshold (PPT), 95% CI 1.76 to 4.16; 1 study, 45 participants). No data were reported on adverse events in the included studies. Laser scar revision versus untreated or placebo controls There is moderate-certainty evidence that pulsed high-intensity laser probably results in a reduction in burn-related pruritus intensity compared with placebo laser (MD -0.51 on a 0 to 1 Itch Severity Scale (ISS), 95% CI -0.64 to -0.38; 1 study, 49 participants). There is moderate-certainty evidence that pulsed high-intensity laser probably reduces pain compared with placebo laser (MD -3.23 VAS, 95% CI -5.41 to -1.05; 1 study, 49 participants). No data were reported on adverse events in the included studies.
AUTHORS' CONCLUSIONS
There is moderate to low-certainty evidence on the effects of 21 interventions. Most studies were small and at a high risk of bias related to blinding and incomplete outcome data. Where there is moderate-certainty evidence, practitioners should consider the applicability of the evidence for their patients.
Topics: Humans; Pruritus; Burns; Randomized Controlled Trials as Topic; Bias; Antipruritics
PubMed: 38837237
DOI: 10.1002/14651858.CD013468.pub2 -
International Journal of... 2024Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disorder mainly affecting joints, yet the systemic inflammation can influence other organs and tissues....
BACKGROUND
Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disorder mainly affecting joints, yet the systemic inflammation can influence other organs and tissues. The objective of this study was to unravel the ameliorative capability of Ondansetron (O) or β-sitosterol (BS) against inflammatory reactions and oxidative stress that complicates Extra-articular manifestations (EAM) in liver, kidney, lung, and heart of arthritic and arthritic irradiated rats.
METHODS
This was accomplished by exposing adjuvant-induced arthritis (AIA) rats to successive weekly fractions of total body γ-irradiation (2 Gray (Gy)/fraction once per week for four weeks, up to a total dose of 8 Gy). Arthritic and/or arthritic irradiated rats were either treated with BS (40 mg/kg b.wt. /day, orally) or O (2 mg/kg) was given ip) or were kept untreated as model groups.
RESULTS
Body weight changes, paw circumference, oxidative stress indices, inflammatory response biomarkers, expression of Janus kinase-2 (JAK-2), Signal transducer and activator of transcription 3 (STAT3), high mobility group box1 (HMGB1), and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), as well as pro- and anti-inflammatory mediators in the target organs, besides histopathological examination of ankle joints and extra-articular tissues. Treatment of arthritic and/or arthritic irradiated rats with BS or O powerfully alleviated changes in body weight gain, paw swelling, oxidative stress, inflammatory reactions, and histopathological degenerative alterations in articular and non-articular tissues.
CONCLUSION
The obtained data imply that BS or O improved the articular and EAM by regulating oxidative and inflammatory indices in arthritic and arthritic irradiated rats.
Topics: Animals; Sitosterols; Lung; Arthritis, Experimental; Kidney; Oxidative Stress; Rats; Liver; Male; Ondansetron; HMGB1 Protein; Heart; Myocardium; Inflammation; Anti-Inflammatory Agents; STAT3 Transcription Factor; Rats, Wistar
PubMed: 38831558
DOI: 10.1177/03946320241260635 -
European Journal of Pharmacology Jun 2024The 5-HT3 receptor and indoleamine 2,3-dioxygenase 1 (IDO1) enzyme play a crucial role in the pathogenesis of depression as their activation reduces serotonin contents...
The 5-HT3 receptor and indoleamine 2,3-dioxygenase 1 (IDO1) enzyme play a crucial role in the pathogenesis of depression as their activation reduces serotonin contents in the brain. Since molecular docking analysis revealed lycopene as a potent 5-HT3 receptor antagonist and IDO1 inhibitor, we hypothesized that lycopene might disrupt the interplay between the 5-HT3 receptor and IDO1 to mitigate depression. In mice, the depression-like phenotypes were induced by inoculating Bacillus Calmette-Guerin (BCG). Lycopene (intraperitoneal; i.p.) was administered alone or in combination with 5-HT3 receptor antagonist ondansetron (i.p.) or IDO1 inhibitor minocycline (i.p.), and the behavioral screening was performed by the sucrose preference test, open field test, tail suspension test, and splash test which are based on the different principles. Further, the brains were subjected to the biochemical analysis of serotonin and its precursor tryptophan by the HPLC. The results showed depression-like behavior in BCG-inoculated mice, which was reversed by lycopene administration. Moreover, prior treatment with ondansetron or minocycline potentiated the antidepressant action of lycopene. Minocycline pretreatment also enhanced the antidepressant effect of ondansetron indicating the regulation of IDO1 activity by 5-HT3 receptor-triggered signaling. Biochemical analysis of brain samples revealed a drastic reduction in the levels of tryptophan and serotonin in depressed animals, which were restored following treatment with lycopene and its combination with ondansetron or minocycline. Taken together, the data from molecular docking, behavioral experiments, and biochemical estimation suggest that lycopene might block the 5-HT3 receptor and consequently inhibit the activity of IDO1 to ameliorate BCG-induced depression in mice.
PubMed: 38830456
DOI: 10.1016/j.ejphar.2024.176707