The Frequently Used Industrial Food Process Additive, Microbial Transglutaminase: Boon or Bane.

Microbial transglutaminase (mTG) is a frequently consumed processed food additive, and use of its cross-linked complexes is expanding rapidly. It was designated as a processing aid and was granted the generally recognized as safe (GRAS) classification decades ago, thus avoiding thorough assessment according to current criteria of toxicity and public health safety. In contrast to the manufacturer's declarations and claims, mTG and/or its transamidated complexes are proinflammatory, immunogenic, allergenic, pathogenic, and potentially toxic, hence raising concerns for public health. Being a member of the transglutaminase family and functionally imitating the tissue transglutaminase, mTG was recently identified as a potential inducer of celiac disease. Microbial transglutaminase and its docked complexes have numerous detrimental effects. Those harmful aspects are denied by the manufacturers, who claim the enzyme is deactivated when heated or by gastric acidity, and that its covalently linked isopeptide bonds are safe. The present narrative review describes the potential side effects of mTG, highlighting its thermostability and activity over a broad pH range, thus, challenging the manufacturers' and distributers' safety claims. The national food regulatory authorities and the scientific community are urged to reevaluate mTG's GRAS status, prioritizing public health protection against the possible risks associated with this enzyme and its health-damaging consequences.

[CONTACT BURNS WITH A HOT WATER BOTTLE FOLLOWING AN ABDOMINOPLASTY. CASE REPORTS AND LITERATURE REVIEW]. / BRÛLURES PAR CONTACT AVEC UNE BOUILLOTE DANS LES SUITES D'UNE ABDOMINOPLASTIE. CAS CLINIQUES ET REVUE DE LA LITTÉRATURE.

Loss of sensitivity in the operated area is common after some plastic surgery procedures and promotes accidental trauma on a daily basis. Several studies showed that a loss of sensitivity is constant after an abdominoplasty. We report here the cases of three 3rd degree burns by contact, at the subumbilical level, with a hot water bottle soon after an abdominoplasty, responsible for significant aesthetic sequelae.

The reprotoxic adverse side effects of neurogenic and neuroprotective drugs: current use of human organoid modeling as a potential alternative to preclinical models.

The management of neurological disorders heavily relies on neurotherapeutic drugs, but notable concerns exist regarding their possible negative effects on reproductive health. Traditional preclinical models often fail to accurately predict reprotoxicity, highlighting the need for more physiologically relevant systems. Organoid models represent a promising approach for concurrently studying neurotoxicity and reprotoxicity, providing insights into the complex interplay between neurotherapeutic drugs and reproductive systems. Herein, we have examined the molecular mechanisms underlying neurotherapeutic drug-induced reprotoxicity and discussed experimental findings from case studies. Additionally, we explore the utility of organoid models in elucidating the reproductive complications of neurodrug exposure. Have discussed the principles of organoid models, highlighting their ability to recapitulate neurodevelopmental processes and simulate drug-induced toxicity in a controlled environment. Challenges and future perspectives in the field have been addressed with a focus on advancing organoid technologies to improve reprotoxicity assessment and enhance drug safety screening. This review underscores the importance of organoid models in unraveling the complex relationship between neurotherapeutic drugs and reproductive health.

A longitudinal evaluation of oxidative stress - mitochondrial dysfunction - ferroptosis genes in anthracycline-induced cardiotoxicity.

BACKGROUND: Antineoplastic medications, including doxorubicin, idarubicin, and epirubicin, have been found to adversely affect the heart due to oxidative stress - mitochondrial dysfunction - ferroptosis (ORMFs), which act as contributing attributes to anthracycline-induced cardiotoxicity. To better understand this phenomenon, the time-resolved measurements of ORMFS genes were analyzed in this study. METHODS: The effect of three anthracycline drugs on ORMFs genes was studied using a human 3D cardiac microtissue cell model. Transcriptome data was collected over 14 days at two doses (therapeutic and toxic). WGCNA identified key module-related genes, and functional enrichment analysis investigated the biological processes quantified by ssGSEA, such as immune cell infiltration and angiogenesis. Biopsies were collected from heart failure patients and control subjects. GSE59672 and GSE2965 were collected for validation. Molecular docking was used to identify anthracyclines's interaction with key genes. RESULTS: The ORMFs genes were screened in vivo or in vitro. Using WGCNA, six co-expressed gene modules were grouped, with MEblue emerging as the most significant module. Eight key genes intersecting the blue module with the dynamic response genes were obtained: CD36, CDH5, CHI3L1, HBA2, HSD11B1, OGN, RPL8, and VWF. Compared with control samples, all key genes except RPL8 were down-regulated in vitro ANT treatment settings, and their expression levels varied over time. According to functional analyses, the key module-related genes were engaged in angiogenesis and the immune system pathways. In all ANT-treated settings, ssGSEA demonstrated a significant down-regulation of angiogenesis score and immune cell activity, including Activated CD4 T cell, Immature B cell, Memory B cell, Natural killer cell, Type 1 T helper cell, and Type 2 T helper cell. Molecular docking revealed that RPL8 and CHI3L1 show significant binding affinity for anthracyclines. CONCLUSION: This study focuses on the dynamic characteristics of ORMFs genes in both human cardiac microtissues and cardiac biopsies from ANT-treated patients. It has been highlighted that ORMFs genes may contribute to immune infiltration and angiogenesis in cases of anthracycline-induced cardiotoxicity. A thorough understanding of these genes could potentially lead to improved diagnosis and treatment of the disease.

Analysis of Allergy and Hypersensitivity Reactions to COVID-19 Vaccines According to the EudraVigilance Database.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic presented a new challenge in modern medicine: the development of vaccines was followed by massive population vaccinations. A few reports on post-vaccination allergic reactions have made patients and medical personnel uneasy as to COVID-19 vaccines' allergic potential. Most of the studies in this area to date have been small, and some that were based on global databases skipped most of the allergic diseases and concentrated only on anaphylaxis. We aimed to analyze the incidence of serious allergic reactions based on the EudraVigilance (EV) database, regardless of the reported symptoms and allergy mechanism. METHODS: The total number of administrated vaccine doses was extracted on 5 October 2023 from Vaccine Tracker and included all administrations since vaccinations began in the European Economic Area (EEA). Data on serious allergic reactions to COVID-19 vaccines were extracted from the EudraVigilance database with the same time point. The code names of 147 allergic symptoms or diseases were used. RESULTS: The frequency of serious allergic reactions per 100,000 administered vaccine doses was 1.53 for Comirnaty, 2.16 for Spikevax, 88.6 for Vaxzevria, 2.11 for Janssen, 7.9 for Novavax, 13.3 for VidPrevtyn Beta, and 3.1 for Valneva. The most prevalent reported reactions were edema (0.46) and anaphylaxis (0.40). Only 6% of these reactions were delayed hypersensitivity-oriented. CONCLUSIONS: The overall frequency of potential serious allergic reactions to COVID-19 is very rare. Therefore, COVID-19 vaccines seem to be safe for human use. The lowest frequency of allergic reaction was observed for Comirnaty and the highest for Vaxzevria.

Myonecrosis as a rare side effect of stereotactic body radiotherapy for bone metastases: Report of two cases and a comprehensive literature review.

Stereotactic body radiotherapy is a highly effective form of radiation therapy for palliation of bone metastases, but it can also lead to rare but severe side effects, such as myonecrosis. According to the literature, the incidence of myonecrosis after stereotactic body radiotherapy is low and mostly dose dependent. It is crucial to consider the potential impact of immunotherapy and other systemic therapies in the assessment. The course of radiation myonecrosis can vary, and corticosteroids or vascular endothelial growth factor inhibitors may potentially play a role in its treatment. Herein, we report two patients presenting with myonecrosis after stereotactic body radiotherapy for bone metastasis.

Ischemic Stroke After Bivalent COVID-19 Vaccination: Self-Controlled Case Series Study.

BACKGROUND: The potential association between bivalent COVID-19 vaccination and ischemic stroke remains uncertain, despite several studies conducted thus far. OBJECTIVE: This study aimed to evaluate the risk of ischemic stroke following bivalent COVID-19 vaccination during the 2022-2023 season. METHODS: A self-controlled case series study was conducted among members aged 12 years and older who experienced ischemic stroke between September 1, 2022, and March 31, 2023, in a large health care system. Ischemic strokes were identified using International Classification of Diseases, Tenth Revision codes in emergency departments and inpatient settings. Exposures were Pfizer-BioNTech or Moderna bivalent COVID-19 vaccination. Risk intervals were prespecified as 1-21 days and 1-42 days after bivalent vaccination; all non-risk-interval person-time served as the control interval. The incidence of ischemic stroke was compared in the risk interval and control interval using conditional Poisson regression. We conducted overall and subgroup analyses by age, history of SARS-CoV-2 infection, and coadministration of influenza vaccine. When an elevated risk was detected, we performed a chart review of ischemic strokes and analyzed the risk of chart-confirmed ischemic stroke. RESULTS: With 4933 ischemic stroke events, we found no increased risk within the 21-day risk interval for the 2 vaccines and by subgroups. However, risk of ischemic stroke was elevated within the 42-day risk interval among individuals aged younger than 65 years with coadministration of Pfizer-BioNTech bivalent and influenza vaccines on the same day; the relative incidence (RI) was 2.13 (95% CI 1.01-4.46). Among those who also had a history of SARS-CoV-2 infection, the RI was 3.94 (95% CI 1.10-14.16). After chart review, the RIs were 2.34 (95% CI 0.97-5.65) and 4.27 (95% CI 0.97-18.85), respectively. Among individuals aged younger than 65 years who received Moderna bivalent vaccine and had a history of SARS-CoV-2 infection, the RI was 2.62 (95% CI 1.13-6.03) before chart review and 2.24 (95% CI 0.78-6.47) after chart review. Stratified analyses by sex did not show a significantly increased risk of ischemic stroke after bivalent vaccination. CONCLUSIONS: While the point estimate for the risk of chart-confirmed ischemic stroke was elevated in a risk interval of 1-42 days among individuals younger than 65 years with coadministration of Pfizer-BioNTech bivalent and influenza vaccines on the same day and among individuals younger than 65 years who received Moderna bivalent vaccine and had a history of SARS-CoV-2 infection, the risk was not statistically significant. The potential association between bivalent vaccination and ischemic stroke in the 1-42-day analysis warrants further investigation among individuals younger than 65 years with influenza vaccine coadministration and prior SARS-CoV-2 infection. Furthermore, the findings on ischemic stroke risk after bivalent COVID-19 vaccination underscore the need to evaluate monovalent COVID-19 vaccine safety during the 2023-2024 season.

A Case Report of Black Hairy Tongue (Melanotrichia Linguae or Lingua Pilosa Nigra).

Black hairy tongue is a benign condition that can be associated with several varying causes. Its etiology is often linked with fungal infection and adverse reactions to various drugs. We present a case of an adult patient who developed a black hairy tongue while on ceftriaxone and pantoprazole for 10 days. The fungus on his tongue was not identified as the causative agent, and recovery was achieved by changing his medications. Ceftriaxone was replaced with trimethoprim/sulfamethoxazole 5 mg/kg intravenous, and pantoprazole was fully stopped. The black lesion on the tongue was observed to regress over several days. Clinicians should be aware of this particular side effect of certain antibiotics.

A Rare Case of Drug-Induced Sweet Syndrome After Pembrolizumab Therapy.

Sweet syndrome is an uncommon inflammatory disorder characterized by the abrupt appearance of painful, erythematous papules, plaques, or nodules on the skin. Fever and leukocytosis frequently accompany the cutaneous lesions. In addition, involvement of the eyes, musculoskeletal system, and internal organs may occur. Sweet syndrome has been associated with a broad range of disorders. There are three subtypes: classical Sweet syndrome, malignancy-associated Sweet syndrome, and drug-induced Sweet syndrome. Classical Sweet syndrome is not associated with malignancy or drugs. It is essentially associated with an upper respiratory infection, gastrointestinal infection, inflammatory bowel disease, and pregnancy. Malignancy-associated Sweet syndrome is associated with hematologic malignancy more than solid malignancy, most commonly with acute myeloid leukemia. Drug-induced Sweet syndrome usually develops approximately two weeks after drug exposure, in patients who lack a prior history of exposure to the inciting drug. Here we are discussing our patient, a 68-year-old male who presented eight weeks after starting chemotherapy with pemetrexed, carboplatin, and pembrolizumab for left lung adenocarcinoma with macular rash. On further investigation with biopsy was found to have neutrophilic dermatitis, hence being diagnosed with drug-induced Sweet syndrome. Histopathology revealed a dermis with infiltration of neutrophils with lekocytoclasia.

Hand Dystonia after Focused Ultrasound Thalamotomy in Essential Tremor.

INTRODUCTION: Magnetic resonance guided focused ultrasound (MRgFUS) thalamotomy is an effective treatment for drug-resistant tremor. The most frequent side effects are ataxia, gait disturbance, paresthesias, dysgeusia, and hemiparesis. Here, we report the first case of thalamic hand dystonia rapidly occurring after MRgFUS thalamotomy of the ventral intermediate nucleus (V.im). CASE PRESENTATION: MRgFUS thalamotomy was performed in a 60-year-old left-handed patient for his disabling medically refractory essential tremor. The intervention resulted in a marked reduction of his action tremor. However, the patient developed an unvoluntary abnormal posture in his left hand a few days after the procedure with difficulty holding a cigarette between his fingers. Brain MRI revealed the expected MRgFUS lesion within the right V.im as well as an extension of the lesion anteriorly to the V.im in the ventro-oralis nucleus. Tractography showed that the lesion disrupted the dentato-rubro-thalamic tract as expected with a lesion suppressing tremor. However, the lesion also was interrupted fibers connecting to the superior frontal and pre-central cortices (primary motor cortex, premotor cortex, and supplementary area). We hypothesized that the interventional MRgFUS thalamotomy was slightly off target, which induced a dysfunction within the cortico-striato-thalamo-cortical network and the cerebello-thalamo-cortical pathway reaching a sufficient threshold of basal ganglia/cerebellum circuitry interference to induce dystonia. CONCLUSION: This rare side effect emphasizes the risk of imbalance within the dystonia network (i.e., basal ganglia-cerebello-thalamo-cortical circuit) secondary to V.im thalamotomy.

Atypical Presentation of Drug Reaction With Eosinophilia and Systemic Symptoms (DRESS) in a Patient on Pembrolizumab: A Case Report.

Pembrolizumab is an immune checkpoint inhibitor that has been associated with numerous immune-mediated adverse effects. Several of these cutaneous side effects may include bullous pemphigoid, Stevens-Johnson syndrome, and drug reaction with eosinophilia and systemic symptoms (DRESS). Other case reports have reported DRESS as a rare side effect of immune checkpoint inhibitors but due to its variable presentation and similarities with other cutaneous diseases, it has proven to be a diagnostic challenge. In addition, no effective methods have been developed to monitor for such adverse skin reactions in patients on immunotherapy. Here, we report a diagnostic challenging case of pembrolizumab-induced blistering lesions that were initially treated as suspected Herpes zoster and/or bullous pemphigoid but further pathology was consistent with DRESS.

Rhabdomyolysis and acute kidney injury after consumption of black seed oil.

PURPOSE: Medicines derived from natural sources have been used for thousands of years throughout the world. Because natural compounds are thought to have less toxic effects and fewer side effects, these products are becoming more popular by the day. CASE REPORT: In this case report, we presented a case of acute kidney injury, rhabdomyolysis, and hepatotoxicity after ingestion of black seed oil. Although black seed oil is widely used around the world, there is currently limited knowledge on its adverse effects. CONCLUSION: It is important to keep in mind that rhabdomyolysis, acute renal damage, and hepatotoxicity might occur following the use of black seed oil. Black seed oil ingestion should be considered when making a differential diagnosis for these conditions in patients suspected of taking herbal products.

[Head-to-head trials in rheumatoid arthritis]. / Head-to-Head-Therapiestudien zur rheumatoiden Arthritis.

BACKGROUND: Head-to-head studies are important to select the optimal treatment in terms of efficacy and side effect profiles when several drugs are available. AIM OF THE WORK: This article describes all studies comparing the use of disease-modifying antirheumatic drugs (DMARD) in rheumatoid arthritis (RA) in head-to-head studies or in which a DMARD was at least included in an active comparison arm. RESULTS: A total of 23 studies comparing DMARDs were identified. These included comparisons of Janus kinase (JAK) inhibitors with methotrexate and with adalimumab as well as the oral surveillance study. DISCUSSION: There are already an exceptionally large number of head-to-head studies in RA, both for comparisons of efficacy and safety of DMARDs. Nevertheless, more such comparative studies are needed, for example to clarify whether adverse events of tofacitinib observed in the oral surveillance study are specific to the JAK 1/JAK 3 inhibitor or are a class effect of all JAK inhibitors.

Genome-wide association study of BNT162b2 vaccine-related myocarditis identifies potential predisposing functional areas in Hong Kong adolescents.

Vaccine-related myocarditis associated with the BNT162b2 vaccine is a rare complication, with a higher risk observed in male adolescents. However, the contribution of genetic factors to this condition remains uncertain. In this study, we conducted a comprehensive genetic association analysis in a cohort of 43 Hong Kong Chinese adolescents who were diagnosed with myocarditis shortly after receiving the BNT162b2 mRNA COVID-19 vaccine. A comparison of whole-genome sequencing data was performed between the confirmed myocarditis cases and a control group of 481 healthy individuals. To narrow down potential genomic regions of interest, we employed a novel clustering approach called ClusterAnalyzer, which prioritised 2,182 genomic regions overlapping with 1,499 genes for further investigation. Our pathway analysis revealed significant enrichment of these genes in functions related to cardiac conduction, ion channel activity, plasma membrane adhesion, and axonogenesis. These findings suggest a potential genetic predisposition in these specific functional areas that may contribute to the observed side effect of the vaccine. Nevertheless, further validation through larger-scale studies is imperative to confirm these findings. Given the increasing prominence of mRNA vaccines as a promising strategy for disease prevention and treatment, understanding the genetic factors associated with vaccine-related myocarditis assumes paramount importance. Our study provides valuable insights that significantly advance our understanding in this regard and serve as a valuable foundation for future research endeavours in this field.

Tigecycline-induced pancreatitis in a patient with recurrent malignancy: a case report and literature review.

Introduction and importance: Drug-induced pancreatitis is an important health issue that makes a minority of causes of acute pancreatitis. Tigecycline-induced pancreatitis is a rare condition with poorly understood mechanism and has a small incident compared to other causes of pancreatitis. Case presentation: The authors present a case of a 39-year-old female patient with acute pancreatitis. Tigecycline was the suspected culprit by exclusion. The patient was managed by keeping her nill per os, rehydration, pain management and discontinuation of the drug. The patient improved gradually. Clinical discussion: Tigecycline-induced acute pancreatitis is a rare but known complication that is mostly seen in patients with chronic renal insufficiency combined with high dose of administration. Onset is usually within 14 days of initiation. Discontinuation of the drug is the most effective intervention in addition to supportive management. Conclusion: Acute pancreatitis should be suspected in any patient presenting with vomiting, abdominal pain and acidosis while on tigecycline. Monitoring of amylase and lipase can be beneficial especially in those with chronic renal insufficiency or those receiving a high dose.

Drug-induced musical hallucination.

Musical hallucination is a rare perceptual phenomenon wherein individuals hear music in the absence of external auditory stimuli. This phenomenon occurs across diverse medical conditions and can be triggered by some drugs. The underlying mechanism of drug-induced hallucination is unknown. This study explores drug-induced musical hallucination through a literature review, aiming to investigate its pathophysiology and potential treatment modalities. A literature search was conducted until January 2024 using databases PubMed, WorldCat, Google Scholar, and DOAJ, with keywords "drugs induced musical hallucination" or "drugs" combined with "musical hallucination." The search yielded 24 articles which met inclusion criteria, encompassing 27 cases. The average patient age was 58.3 years, with 67.9% females. Prevalent conditions among cases included hearing impairments, psychiatric disorders, cancers, and neurodegenerative conditions. Common trigger drugs comprised antidepressants, opioids, anti-Parkinson drugs, ketamine, and voriconazole. Musical hallucination descriptions varied widely, and 6 patients reported concurrent visual hallucinations. The onset of symptoms ranged from 75 min to 240 days. Treatment strategies included termination of trigger drugs, dosage reduction, alteration of administration routes or formula, switching to similar drugs, or addition of antidepressants, sedatives, or atypical antipsychotic medications. Musical hallucinations completely disappeared in 24/27 (88.9%) patients but continued in 3/27 (11.1%) patients. The current study concludes that drug-induced musical hallucination may arise from altering neurotransmitter/receptor balance and intricate interactions between trigger drugs and underlying conditions.

The Effect of Electroconvulsive Therapy on Frontal QRS-T Angle in Psychiatric Patients.

Introduction: Electroconvulsive therapy (ECT) is one of the biological therapies that is well tolerated and has a low risk of complications. Acute cardiovascular complications related to ECT such as ventricular arrhythmia, myocardial infarction and cardiac arrest have been recorded. Increased frontal QRS-T (fQRS-T) angle was associated with ventricular arrhythmia, sudden cardiac death and total mortality. In this study, we aimed to evaluate the effect of ECT on the myocardium using electrocardiography (ECG) parameters such as fQRS-T angle, QRS duration, QT and QTc interval. Methods: A total of 108 patients diagnosed with bipolar disorder (n=36), depressive disorder (n=70) and schizophrenia (n=2) who underwent ECT were included in this study. 12-lead surface ECG of all patients were taken before the ECT, 15 min. after ECT and 24 hour after ECT. Results: QRS duration, QT interval and corrected QT (QTc) interval were not changed significantly during the follow-up period. However, we found that, fQRS-T angle was significantly increased 15 minutes after ECT compared to baseline angle (p<0.001). We also detected that this increase in fQRS-T angle 15 minutes after ECT was significantly reduced 24 hours after ECT (p=0.031). Meanwhile, there was no significant difference between baseline and 24th hour fQRS-T angle (p=0.154). Conclusions: In our study, a significant increase in fQRS-T angle was observed 15 min after ECT. However, the fQRS-T angle was found to return to normal after 24 hours. Our findings may indicate that ECT does not have a permanent side effect on the risk of cardiovascular events according to the fQRS-T angle.

Tobacco smoking influences the side effects of radiation therapy-managed patients with various malignancies: A systematic review.

BACKGROUND: Tobacco smoking may decrease the effectiveness of radiation therapy. This is because tobacco smoking can cause inflammation and damage to surrounding tissues, which may interfere with radiation delivery to the tumor. Our aim of this study is to investigate the effect of tobacco smoking use on complications in radiotherapy as a systematic review. METHOD: The articles searched from the MEDLINE, PubMed, EMBASE, and Web of Science databases. The search terms used were "radiotherapy", "outcome", "radiation therapy", "tobacco", "smoking", "complications", "side effects", "cancer", and "malignancy". PRISMA check list was used to assess the overall quality of evidence for each outcome. RESULT: The outcomes of radiotherapy-inducing tobacco smoking in smokers are more than non-smokers including; high SPC (second primary cancer), decreased median overall survival, higher infections during treatment, increased fatigue (p = 0.027), increased pain (p = 0.009), poorer cognitive function (0.041), affected mouth opening (0.049), more speech disturbances (p = 0.017), higher metastasis risk (p = 0.031 and 0.019), higher locoregional recurrence risk (p = 0.027), oral mucositis (p = 0.03), mucositis severity related to higher tobacco exposure (p = 0.008), severe acute radiation skin reactions, and myocardial infarction. DISCUSSION: Tobacco smoking appears to be the most significant modifiable factor influencing cancer treatment outcomes. As such, healthcare providers should take detailed notes on patients' smoking histories during both routine and future clinical studies. Beyond immediate cessation, cancer patients should undertake comprehensive smoking cessation programs. These programs can significantly boost the efficacy of radiotherapy and enhance overall patient outcomes.

Diurnal variation of cisplatin-induced renal toxicity in ICR mice.

Cisplatin (CDDP) is a platinum-based anticancer drug widely prescribed for its effectiveness in treating various forms of cancer. However, its major side effect is nephrotoxicity. Although several methods have been developed to mitigate CDDP-induced nephrotoxicity, an optimal approach has yet to be established. This study aimed to investigate the "chronotoxicity" of CDDP as a potential strategy to reduce its side effects. Male ICR mice were treated with CDDP (20 mg/kg, intraperitoneal injection, one shot) at zeitgeber time (ZT) 2 or ZT14 (light or dark phase). After 72 h, we collected plasma and kidney and evaluated several markers. We found that body weight change between ZT2 and ZT14 by CDDP was comparable. In contrast, many toxicological factors, such as plasma blood urine nitrogen, plasma creatinine, renal oxidative stress (malondialdehyde), DNA damage (γH2AX), acute kidney injury biomarker (KIM-1), and inflammation (Tnfα), were significantly induced at ZT14 compared to than that of ZT2. Our present data suggested that chronotoxicology might provide beneficial information on the importance of administration timings for toxic evaluations and unacceptable side effects.