Journal of Applied Toxicology最新文献

{"title":"Arsenic-Induced Inflammatory Response via ROS-Dependent Activation of ERK/NF-kB Signaling Pathways: Protective Role of Natural Polyphenol Tannic Acid","authors":"Sehal Mishra,&nbsp;Mahendran Botlagunta,&nbsp;Subbiah Rajasekaran","doi":"10.1002/jat.4748","DOIUrl":"10.1002/jat.4748","url":null,"abstract":"<div>\u0000 \u0000 <p>Arsenic (As), a highly toxic metalloid, is present throughout our environment as a result of both natural and human-related activities. Furthermore, As exposure could lead to a persistent inflammatory response, which may facilitate the pathogenesis of several diseases in various organs. This study was performed to investigate the As-induced inflammatory response and the underlying molecular mechanisms in vitro. Further, the anti-inflammatory effects of a natural dietary polyphenol tannic acid (TA) were also explored. In human normal bronchial (BEAS-2B), adenocarcinoma alveolar basal (A549), and murine macrophages (J774) cell lines, a trivalent form of As (as As³⁺) exposure markedly induced the expression of various pro-inflammatory mediators (cytokines and chemokines). Additionally, it was found that As³⁺ exposure induced reactive oxygen species (ROS) generation and activation of the nuclear factor-kappa B (NF-kB) p65 and extracellular signal-regulated kinase (ERK)1/2 pathways in BEAS-2B cells. As expected, the blockade of either ERK1/2 (PD98059) or NF-kB p65 (IMD0354), or both pathways attenuated As³⁺-induced pro-inflammatory mediators release. Interestingly, pre-treatment with ROS inhibitor <i>N</i>-acetylcysteine (NAC) attenuated activation of ERK/NF-kB pathways, suggesting that ROS have a critical role in pathway's activation and subsequent inflammatory response. Further, TA pre-treatment effectively attenuated As³⁺-induced inflammatory response by suppressing ROS production and ERK/NF-kB signaling pathways activation. Therefore, this study provides scientific evidence for the anti-inflammatory activities of TA and the underlying molecular mechanisms.</p>\u0000 </div>","PeriodicalId":15242,"journal":{"name":"Journal of Applied Toxicology","volume":"45 5","pages":"795-807"},"PeriodicalIF":2.7,"publicationDate":"2024-12-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143005773","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Crude Oil–Induced Reproductive Disorders in Male Goldfish: Testicular Histopathology, Sex Steroid Hormones, and Sperm Swimming Kinematics","authors":"Mahboubeh Mahlouji,&nbsp;Sayyed Mohammad Hadi Alavi,&nbsp;Jahanbakhsh Ghasemi,&nbsp;Amir Hossein Jalili,&nbsp;Mansour Torfi Mozanzadeh,&nbsp;Songpei Zhang,&nbsp;Nururshopa Eskander Shazada,&nbsp;Ian A. E. Butts,&nbsp;Seyed Hossein Hoseinifar,&nbsp;Otomar Linhart","doi":"10.1002/jat.4745","DOIUrl":"10.1002/jat.4745","url":null,"abstract":"<div>\u0000 \u0000 <p>Crude oil contamination has been shown to impair reproduction in aquatic animals through carcinogenic and genotoxic properties. Here, we assessed the endocrine-disrupting function of crude oil on male reproductive system based on testicular histology, sex steroid hormones, and fertility endpoints in adult male goldfish (<i>Carassius auratus</i>), which were exposed to 0.02- to 2-mg/L crude oil for 21 days (Experiment #1) or to 5- to 250-mg/L crude oil for 9 days (Experiment #2). The crude oil contained 0.22-mg/L nickel (Ni), 1.10-mg/L vanadium (V), and 12.87-mg/L polycyclic aromatic hydrocarbons (PAHs). Twenty-four hours after adding crude oil, the sum of PAHs ranged from 0.30 to 2.28 μg/L in the aquaria containing 0.02- and 250-mg/L crude oil, respectively. Water analyses for heavy metals in Experiment #2 showed high concentrations (mg/L) of Ni (0.07–0-09) and V (0.10–0.21). For both experiments, exposure to crude oil did not impact gonadosomatic index; however, testes showed histopathological defects including hyperplasia or hypertrophy of Sertoli cells, depletion of the Leydig cells, necrosis of germ cells, and fibrosis of lobular wall. In Experiment #1, sperm production and motility, testosterone (T), and 17β-estradiol (E₂) were not significantly different among treatments. In Experiment #2, the number of spermiating males decreased by ~50% following exposure to 250-mg/L crude oil. Sperm production, motility kinematics, T, and the T/E₂ ratio significantly decreased in males exposed to ≥ 50-mg/L crude oil; however, E₂ remained unchanged. Results show crude oil–induced imbalance of sex steroid hormones disrupts spermatogenesis resulting in diminished sperm production and motility.</p>\u0000 </div>","PeriodicalId":15242,"journal":{"name":"Journal of Applied Toxicology","volume":"45 5","pages":"767-782"},"PeriodicalIF":2.7,"publicationDate":"2024-12-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142893698","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"28-Day Repeated Dose Toxicity and Toxicokinetics Study on Dihydroartemisinin (DHA) in SD Rats","authors":"Yang  Jian,&nbsp;Peng  Yue,&nbsp;Hongqun  Qiao","doi":"10.1002/jat.4738","DOIUrl":"10.1002/jat.4738","url":null,"abstract":"<div>\u0000 \u0000 <p>Dihydroartemisinin (DHA) is an effective antimalarial drug with potential antitumor efficacy, yet toxicological information is limited. The present study was designed to evaluate the potential toxicity of oral DHA. DHA was administered orally by gavage to SD rats at doses of 0, 25, 50, and 75/60 mg/kg b.w./day for 28 days, followed by a 4-week recovery period. Concomitant toxicokinetics was also evaluated. Due to potential toxicity affecting survival, only the female top dose was adjusted from 75 to 60 mg/kg on study day 14 (D14). Female rats in the low-dose group and male rats in the low- and medium-dose groups did not show any signs of toxicity. In contrast, male rats in the high-dose group and female rats in the medium- and high-dose groups showed significant toxic effects, including weight loss, hair loss, and gastrointestinal reactions (soft stools, perianal dirt, and fecal abnormalities). At the end of administration, female rats in the 75/60 (dose-adjusted) mg/kg dose group had significantly higher reticulocytes (Ret% and RETIC) and alanine aminotransferase (ALT), increased liver weights, and significantly lower hemoglobin (HGB). In addition, histopathology showed mild vacuolation of hepatocytes. These findings suggest that female rats have a greater toxic response than males, and toxicokinetics further demonstrate this sex difference. However, the toxic effects of DHA were reversed at the end of the 4-week recovery period. Therefore, the liver was identified as the primary target organ. The no-observed-adverse-effect-level (NOAEL) was 25 and 50 mg/kg b.w./day in female and male rats, respectively.</p>\u0000 </div>","PeriodicalId":15242,"journal":{"name":"Journal of Applied Toxicology","volume":"45 5","pages":"755-766"},"PeriodicalIF":2.7,"publicationDate":"2024-12-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142877285","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Research Progress on the Correlation Between Atmospheric Particulate Matter and Autism","authors":"Yaqian Xiao,&nbsp;Wang Xiang,&nbsp;Xuerui Ma,&nbsp;Aijia Zheng,&nbsp;Dechang Rong,&nbsp;Nimeng Zhang,&nbsp;Ning Yang,&nbsp;Hasan Bayram,&nbsp;George H. Lorimer,&nbsp;Jun Wang","doi":"10.1002/jat.4722","DOIUrl":"10.1002/jat.4722","url":null,"abstract":"<div>\u0000 \u0000 <p>Autism spectrum disorder (ASD) is a neurodevelopmental disorder caused by the interaction of genetic and complex environmental factors. The prevalence of autism has dramatically increased in countries and regions undergoing rapid industrialization and urbanization. Recent studies have shown that particulate matter (PM) in air pollution affects the development of neurons and disrupts the function of the nervous system, leading to behavioral and cognitive problems and increasing the risk of ASD. However, research on the mechanism of environmental factors and ASD is still in its infancy. On this basis, we conducted a literature search and analysis to review epidemiological studies on the correlation between fine particulate matter (PM_2.5) and inhalable particulate matter (PM₁₀) and ASD. The signaling pathways and pathogenic mechanisms of PM in synaptic injury and neuroinflammation are presented, and the mechanism of the ASD candidate gene <i>SHANK</i>3 was reviewed. Additionally, the different sites of action of different particles in animal models and humans were highlighted, and the differences of their effects on the pathogenesis of ASD were explained. We summarized the aetiology and mechanisms of PM-induced autism and look forward to future research breakthroughs in improved assessment methods, multidisciplinary alliances and high-tech innovations.</p>\u0000 </div>","PeriodicalId":15242,"journal":{"name":"Journal of Applied Toxicology","volume":"45 7","pages":"1203-1222"},"PeriodicalIF":2.7,"publicationDate":"2024-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142864277","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Study of Serum Metabolic Biomarkers and Prediction Models of Cantharidin-Induced Nephrotoxicity in Rats Based on Dynamic Metabolomics","authors":"Weina Cheng,&nbsp;Wenzhong Feng,&nbsp;Guanghuan Tian,&nbsp;Jingxian Liu,&nbsp;Zhixun Bai,&nbsp;Ming Yu,&nbsp;Rong Yan,&nbsp;Liu Liu,&nbsp;Yanmei He,&nbsp;Xiaofei Li,&nbsp;Jianyong Zhang","doi":"10.1002/jat.4743","DOIUrl":"10.1002/jat.4743","url":null,"abstract":"<div>\u0000 \u0000 <p>The clinical application of cantharidin (CTD) is seriously limited due to its nephrotoxicity. Therefore, this study aims to investigate sensitive biomarkers for the evaluation and prediction of nephrotoxicity induced by CTD in rat. A total of 80 rats were randomly divided into four groups: control group and three doses of CTD groups. After 0, 1, 5, 15, and 28 days of intragastric administration, rat serum and urine were collected for biochemical indexes, then serum was used for metabolomic analyses, and rat kidney was collected for pathological and ultrastructural observation. The levels of serum crea (Scr), blood urea nitrogen (BUN), urea, urine crea (Ucrea), and urinary microalbumin (UmALB) were significantly increased after administration of different doses of CTD (<i>p</i> &lt; 0.05). Additionally, histopathology and cell ultrastructure observation of kidney showed significant cell inflammatory infiltration and glomerular edema. Seven metabolic biomarkers including 6-hydroxymelatonin were significantly disturbed by CTD. The CatBoost Classifier prediction model was used to establish the CTD nephrotoxicity prediction model, and the prediction accuracy and precision were 0.645 and 0.640, respectively. Moreover, 6-hydroxymelatonin was found to be most useful biomarkers for evaluating the CTD nephrotoxicity. Finally, the seven metabolic biomarkers were found mainly involved in pyruvate metabolism, pantothenate and CoA biosynthesis.</p>\u0000 </div>","PeriodicalId":15242,"journal":{"name":"Journal of Applied Toxicology","volume":"45 5","pages":"736-754"},"PeriodicalIF":2.7,"publicationDate":"2024-12-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142828716","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pilot Study of Acute and Subchronic Oral Toxicological Biosafety Evaluation of Resorcinol-Formaldehyde Aerogel Nanomaterial in Kunming Mice","authors":"Guangzhen Zheng,&nbsp;Yong Zhu,&nbsp;Bingmin Wu,&nbsp;Xiaoyuan Xu,&nbsp;Juanjuan Cheng,&nbsp;Yan Liu,&nbsp;Song Huang,&nbsp;Jing Chen,&nbsp;Qingping Xiong,&nbsp;Jihang Chen","doi":"10.1002/jat.4735","DOIUrl":"10.1002/jat.4735","url":null,"abstract":"<div>\u0000 \u0000 <p>Resorcinol-formaldehyde aerogel (RFa) is a unique nanomaterial composed of polymer nanoparticles with a three-dimensional network structure. Our previous studies have demonstrated its application in the separation and purification of alkaloids, and we are exploring its application potential as the drug delivery carrier. Therefore, it is necessary to comprehensively understand the in vivo toxicity profile of RFa and evaluate its oral biosafety. In this work, we systematically evaluated the in vivo acute toxicity and subchronic oral toxicity of RFa in both male and female Kunming mice. During the 14-day acute toxicity test, the dose administered (<i>M</i> = 580 mg/kg) was converted from the clinical dose of adsorbed alkaloids on RFa. The mice were gavaged only once and were observed continuously for 14 days. There were no abnormalities, and pathological changes in the major organs (heart, liver, spleen, lungs, kidneys, testes, and ovaries) were detected, followed by the 12-week subchronic toxicity test at the dose of 1/4<i>M</i>, 1/2<i>M</i>, and <i>M</i>. All mice were administered orally once daily and regularly observed throughout the experimental period. As a result, no abnormalities were found in body weights, food intake, and organ coefficients. Tissue section revealed no pathological changes in the major organs. In addition, there were no significant differences in hematological, blood biochemical, and coagulation parameters in both male and female mice compared to control group. These results showed that RFa was well tolerated at these dosage levels and did not cause significant toxic effects in Kunming mice. This study, as part of a broad research program on the biosafety of aerogel nanomaterials, provided the biosafety assurance for the subsequent study of RFa in biomedical applications.</p>\u0000 </div>","PeriodicalId":15242,"journal":{"name":"Journal of Applied Toxicology","volume":"45 5","pages":"721-735"},"PeriodicalIF":2.7,"publicationDate":"2024-12-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142818160","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Toxicological Safety Assessment of Heat-Treated Lactiplantibacillus plantarum OLL2712 as a Food Ingredient","authors":"Ryan M. Parente,&nbsp;Takayuki Toshimitsu,&nbsp;Youko Nakamoto,&nbsp;Tomoyasu Taguchi","doi":"10.1002/jat.4723","DOIUrl":"10.1002/jat.4723","url":null,"abstract":"<div>\u0000 \u0000 <p><i>Lactiplantibacillus plantarum</i> is a Gram-positive, bacilli-shaped bacterium commonly found in fermented foods and the human gastrointestinal tract. Heat-treatment of <i>L. plantarum</i> OLL2712 prior to consumption has been found to have positive health effects. However, a full toxicological evaluation of heat-treated <i>L. plantarum</i> OLL2712 cells (heat-treated OLL2712) has not been conducted. In this regard, heat-treated OLL2712 was evaluated for use as an ingredient in food and dietary supplements using a panel of toxicological tests including genotoxic and subchronic studies. Heat-treated OLL2712 did not show any genotoxicity based on an in vitro mammalian chromosomal aberration test and in vivo mouse micronucleus assay up to 8.0 × 10⁹ cells/mL and 6.4 × 10¹² cells/kg, respectively. In the acute oral toxicity study, no toxic effects were observed at 5 × 10¹¹ cells/kg body weight. In the 13-week subchronic toxicity study, rats were administered (via gavage) heat-treated OLL2712 at concentrations of 0.5 × 10¹¹, 1.5 × 10¹¹, and 5 × 10¹¹ cells/kg body weight. Administration did not significantly impact mortality, body weight, food consumption, ophthalmology, hematology, clinical chemistry, coagulation, urinalysis, and macroscopic or microscopic findings. The no-observed-adverse-effect level of heat-treated OLL2712 in both sexes was 5 × 10¹¹ cells/kg body weight/day, the highest dose tested.</p>\u0000 </div>","PeriodicalId":15242,"journal":{"name":"Journal of Applied Toxicology","volume":"45 4","pages":"694-710"},"PeriodicalIF":2.7,"publicationDate":"2024-12-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142813067","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Blockade of Voltage-Gated K+ Channels in Rabbit Coronary Arterial Smooth Muscle Cells by the Antipsychotic Drug Zotepine","authors":"Wenwen Zhuang,&nbsp;Minju Park,&nbsp;Junsu Jeong,&nbsp;Hye Ryung Kim,&nbsp;YeEun Jang,&nbsp;Hongzoo Park,&nbsp;Sunghun Na,&nbsp;Hongliang Li,&nbsp;Won Sun Park","doi":"10.1002/jat.4740","DOIUrl":"10.1002/jat.4740","url":null,"abstract":"<div>\u0000 \u0000 <p>Zotepine is a second-generation antipsychotic that demonstrates significant efficacy in antagonizing D₂ and 5-HT_2A receptors. Although clinical investigations have shown that administering zotepine is associated with an increased prevalence of hyperglycemia and a heightened risk of cardiovascular disease, the side effects of zotepine on voltage-gated K⁺ (Kv) channels have not been established. Zotepine suppressed the vascular Kv channels in rabbit coronary arterial smooth muscle cells in a concentration-dependent manner, with an IC₅₀ of 5.3 ± 0.4 μM and a Hill coefficient of 1.6 ± 0.2. The decay rate of inactivation was significantly accelerated by zotepine. Applying zotepine (10 μM) shifted the steady-state inactivation curve in a negative direction. Applying train pulses at 1 and 2 Hz resulted in a progressive increase in blockage of the Kv currents by zotepine. Furthermore, zotepine prolonged the recovery time from inactivation. Although pretreatment with the Kv2.1 subtype inhibitor stromatoxin-1 and the Kv7 subtype inhibitor linopirdine did not change the degree of zotepine-induced inhibition of Kv currents, pretreatment with the Kv1.5 channel inhibitor DPO-1 decreased the inhibitory effects of zotepine on Kv currents. Zotepine also induced membrane depolarization. These results indicate that zotepine inhibits Kv currents (mainly Kv1.5 subtype) in dose-, time-, and use (state)-dependent manners by changing the steady-state inactivation curve.</p>\u0000 </div>","PeriodicalId":15242,"journal":{"name":"Journal of Applied Toxicology","volume":"45 4","pages":"685-693"},"PeriodicalIF":2.7,"publicationDate":"2024-12-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142800307","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Behavioral Alterations in Mice Exposed to Manganese via Drinking Water: Effects of Sex and a Lipopolysaccharide Challenge","authors":"Helaina D. Ludwig,&nbsp;Jessica M. Carpenter,&nbsp;Nikolay M. Filipov","doi":"10.1002/jat.4739","DOIUrl":"10.1002/jat.4739","url":null,"abstract":"<p>Manganese (Mn) is an essential and important metal; however, overexposures lead to adverse neurological outcomes. Nonoccupational Mn overexposure occurs primarily through consumption of Mn-contaminated drinking water (DW). Sex differences in terms of nervous and immune systems' responsiveness to excessive Mn in the DW are understudied. Thus, this study investigated behavioral and sex differences in response to Mn DW treatment (0.4 g Mn/L for up to 8 weeks) and a lipopolysaccharide (LPS) challenge of adult C57BL/6 mice with GFP-tagged monocytes/microglia. After 6 weeks, in motor function tests, Mn exposure resulted in decreased activity and gait deficits. In two different mood tests (open field test [OFT]/elevated zero maze), Mn-exposed mice exhibited decreased fear/anxiety-like behavior. Two weeks after behavioral assessment, when mice were challenged with LPS, circulating inflammatory cytokines, and acute phase proteins increased in both sexes. After 8 weeks of Mn exposure, liver and brain Mn levels were increased, but Mn alone did not affect circulating cytokines in either sex. Notably, Mn-exposed/LPS-challenged males had potentiated plasma cytokine output, whereas the reverse was seen in females. Males, but not females, continued to exhibit increased fearlessness (i.e., increased OFT center time), even when challenged with LPS. Overall, our results show that Mn DW exposure increases brain Mn levels and it leads to behavioral alterations in both sexes. However, males might be more susceptible to the effect of Mn on mood, and this effect is recalcitrant to an inflammagen challenge. Mn augmented post-LPS cytokine production only in males, further indicating that important Mn effects are sex-biased.</p>","PeriodicalId":15242,"journal":{"name":"Journal of Applied Toxicology","volume":"45 4","pages":"669-684"},"PeriodicalIF":2.7,"publicationDate":"2024-12-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jat.4739","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142794831","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Evaluation of the Neuroprotective Effects of Idebenone in an Experimental Carbon Monoxide Poisoning Model","authors":"Hulya Karakus,&nbsp;Ozlem Bulbul,&nbsp;Ali Kulaber,&nbsp;Huseyin Yaman,&nbsp;Sinan Pasli,&nbsp;Melih Imamoglu,&nbsp;Yunus Karaca,&nbsp;Engin Yenilmez,&nbsp;Vildan Ozer","doi":"10.1002/jat.4742","DOIUrl":"10.1002/jat.4742","url":null,"abstract":"<div>\u0000 \u0000 <p>Carbon monoxide (CO) poisoning is among the main causes of poisoning-related mortality and morbidity, primarily affecting the central nervous system and leading to delayed neurological sequelae. Idebenone exerts antioxidant and neuroprotective effects. In this study, we aimed to evaluate the specific neuroprotective effects of idebenone against CO poisoning. Forty female Wistar Albino rats were used in this study. Except the controls, the other rats inhaled 5000 ppm CO until a change in consciousness was observed. Rats with carboxyhemoglobin concentrations over 20% in blood samples collected from the tail vein were considered successful acute CO poisoning models. The rats were divided into five groups: healthy control (HC; group 1), CO + saline (CO-S; group 2), CO + 100 mg/kg idebenone (CO-I₁₀₀; group 3), CO + 200 mg/kg idebenone (CO-I₂₀₀; group 4), and CO + 300 mg/kg idebenone (CO-I₃₀₀; group 5). Pre-determined doses of idebenon were orally administered to the rats at 24-h intervals for 5 days. The rats were anesthetized and sacrificed 24 h after the last drug dose. Histopathological and biochemical parameters were examined in the blood and hippocampus samples of the rats. Histopathological grading of neurons in the hippocampus revealed that the CO-S group exhibited the highest number of grade 1, 2, and 3 degenerative cells (all <i>p</i> = 0.001). Apoptotic index was the highest in the CO-S group and significantly low in the idebenone-treated groups (<i>p</i> = 0.001). Neuron-specific enolase and malondialdehyde levels and oxidative stress index were significantly lower in both the hippocampus and serum samples of the idebenone-treated groups than in those of the CO-S group (all <i>p</i> values = 0.001). Overall, idebenone inhibited degeneration due to CO-induced brain damage and exerted neuroprotective effects against oxidative stress in rats.</p>\u0000 </div>","PeriodicalId":15242,"journal":{"name":"Journal of Applied Toxicology","volume":"45 4","pages":"659-668"},"PeriodicalIF":2.7,"publicationDate":"2024-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142785599","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}