Forensic Toxicology最新文献

{"title":"Death due to unrecognized intoxication of nifedipine in an adult.","authors":"Prasanna Appuhamy, Siddihalu Lakshitha Madunil","doi":"10.1007/s11419-024-00704-1","DOIUrl":"https://doi.org/10.1007/s11419-024-00704-1","url":null,"abstract":"<p><strong>Purpose: </strong>Diagnosis of drug intoxication in the medico-legal autopsy is challenging due to many factors such as non-specific clinical features and non-specific, inconclusive autopsy findings, etc. Thus, deaths due to drug intoxication can be misclassified in a low-resource setting where post-mortem toxicology testing is selective. The paper presents a fatal case of unrecognized nifedipine intoxication in an adult where the manner of death was undetermined after extensive investigation.</p><p><strong>Method: </strong>The liquid-liquid extraction using chloroform was carried out on a blood sample spiked with nifedipine. Subsequently, the post-mortem blood sample was analyzed and quantified using gas chromatography-mass spectrometry with electron ionization technique.</p><p><strong>Results: </strong>The patient before death had symptoms, such as trismus, vomiting, and dizziness. The initial blood pressure and pulse rate were 94/56 mm Hg and 110 beats per minute, respectively. The respiratory rate was 20 breaths per minute. The post-mortem examination revealed no pathological changes or injuries in any organs. Upon histopathological examination, no significant findings that could have led to death were observed in any of the organs. The level of nifedipine in the peripheral blood, 0.645 μg/ml was determined to be either  close to or exceeding the reported fatal dose. The cause of death was ascertained as acute nifedipine intoxication.</p><p><strong>Conclusion: </strong>It is crucial to accurately determine the cause of death in cases that pose a significant threat to public health. This case highlights the challenges faced by forensic pathologists in scientifically ascertaining the cause of death accurately, especially in intoxication deaths, and the importance of comprehensive toxicology testing services including analytical toxicology for the integrity of the medico-legal death investigation system.</p>","PeriodicalId":12329,"journal":{"name":"Forensic Toxicology","volume":null,"pages":null},"PeriodicalIF":2.8,"publicationDate":"2024-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142282792","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":"Elucidation of toxic effects of 1,2-diacetylbenzene: an in silico study","authors":"Hai Duc Nguyen, Giang Huong Vu, Linh Thuy Hoang, Min-Sun Kim","doi":"10.1007/s11419-024-00702-3","DOIUrl":"https://doi.org/10.1007/s11419-024-00702-3","url":null,"abstract":"<h3 data-test=\"abstract-sub-heading\">Purpose</h3><p>We aimed to explore the metabolite products of 1,2-diacetylbenzene (DAB) and investigate their harmful effects, physicochemical properties, and biological activities, along with those of DAB itself.</p><h3 data-test=\"abstract-sub-heading\">Methods</h3><p>Key approaches included MetaTox, PASS online, ADMESWISS, ADMETlab 2.0, molecular docking, and molecular dynamic simulation to identify metabolites, toxic effects, Lipinski’s rule criteria, absorption, distribution, metabolism, and excretion properties, interactions with cytochrome (CYP) 450 isoforms, and the stability of the DAB-cytochrome complex.</p><h3 data-test=\"abstract-sub-heading\">Results</h3><p>A total of 13 metabolite products from DAB were identified, involving Phase I reactions (aliphatic hydroxylation, epoxidation, oxidative dehydrogenation, and hydrogenation) and Phase II reactions (oxidative sulfation and methylation). Molecular dynamics and modeling revealed a stable interaction between CYP1A2 and DAB, suggesting the involvement of CYP1A2 in DAB metabolism. All studied compounds adhered to Lipinski’s rule, indicating their potential as inducers or activators of toxic mechanisms. The physicochemical parameters and pharmacokinetics of the investigated compounds were consistent with their harmful effects, which included neurotoxic, nephrotoxic, endocrine disruptor, and hepatotoxic consequences due to their high gastrointestinal absorption and ability to cross the blood–brain barrier. Various CYP450 isoforms exhibited different functions, and the compounds were found to act as superoxide dismutase inhibitors, neuropeptide Y2 antagonists, glutaminase inhibitors, and activators of caspases 3 and 8. DAB and its metabolites were also associated with apoptosis, oxidative stress, and neuroendocrine disruption.</p><h3 data-test=\"abstract-sub-heading\">Conclusion</h3><p>The toxic effects of DAB and its metabolites were predicted in this study. Further research is warranted to explore their effects on other organs, such as the liver and kidneys, and to validate our findings.</p>","PeriodicalId":12329,"journal":{"name":"Forensic Toxicology","volume":null,"pages":null},"PeriodicalIF":2.2,"publicationDate":"2024-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142252049","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":"Bioinformatics-driven untargeted metabolomic profiling for clinical screening of methamphetamine abuse","authors":"Elif Kesmen, Hızır Asliyüksek, Ahmet Nezih Kök, Cem Şenol, Semih Özli, Onur Senol","doi":"10.1007/s11419-024-00703-2","DOIUrl":"https://doi.org/10.1007/s11419-024-00703-2","url":null,"abstract":"<h3 data-test=\"abstract-sub-heading\">Purpose</h3><p>Amphetamine-type stimulants are very common, and their usage is becoming a very big social problem all over the world. Thousands of addicts encounter several health problems including mental, metabolic, behavioral and neurological disorders. In addition to these, there are several reports about the elevated risk of tendency on committing criminal cases by addicted persons. Hence, methamphetamine addiction is not only an individual health problem but also a social problem. In our study, we aimed to investigate the pathogenesis of chronic usage of methamphetamine via untargeted metabolomics approach.</p><h3 data-test=\"abstract-sub-heading\">Methods</h3><p>38 plasma samples were carefully collected and extracted for untargeted metabolomics assay. A liquid–liquid extraction was performed to get as much metabolite as possible from the samples. After the extraction procedure, samples were transferred into vials and they were evaluated via time of flight mass spectrometry instrument.</p><h3 data-test=\"abstract-sub-heading\">Results</h3><p>Significantly, altered metabolites were identified by the fold analysis and Welch’s test between the groups. 42 different compounds were annotated regarding to data-dependent acquisition method. Pathway analysis were also performed to understand the hazardous effect of methamphetamine on human body.</p><h3 data-test=\"abstract-sub-heading\">Conclusion</h3><p>It has been reported that drug exposure may affect several metabolic pathways for amino acids, fats, energy metabolism and vitamins. An alternative bioinformatic model was also developed and validated in order to predict the chronic methamphetamine drug users in any criminal cases. This generated model passes the ROC curve analysis and permutation test and classify the controls and drug users correctly by evaluating the metabolic alterations between the groups.</p>","PeriodicalId":12329,"journal":{"name":"Forensic Toxicology","volume":null,"pages":null},"PeriodicalIF":2.2,"publicationDate":"2024-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142252052","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":"Postmortem distribution of ropivacaine and its metabolite in human body fluids and solid tissues by GC–MS/MS using standard addition method","authors":"Xiaolong Zhang, Shuyun Wang, Yuxuan Chen, Jie Gu, Mengchao Wang, Yinyin Dai, Kundi Zhao, Yue Wang, Amin Wurita, Koutaro Hasegawa","doi":"10.1007/s11419-024-00695-z","DOIUrl":"https://doi.org/10.1007/s11419-024-00695-z","url":null,"abstract":"<h3 data-test=\"abstract-sub-heading\">Purpose</h3><p>An analytical method was developed for determining ropivacaine and its main metabolite, 3-hydroxyropivacaine in biomedical samples using gas chromatography-tandem mass spectrometry (GC–MS/MS). Then, this established method was applied to investigate the distribution of ropivacaine and its metabolite in human fluids and solid tissues obtained from an authentic case ropivacaine involved.</p><h3 data-test=\"abstract-sub-heading\">Methods</h3><p>The fluid sample was added acetonitrile, and solid tissue was homogenized using a freezer mill and then added into acetonitrile. Then, an internal standard solution was added to the mixtures. The mixture was centrifuged at 12,000 × g for 5 min, and the upper layer of acetonitrile was transferred to magnesium sulfate and octadecyl silica (C18) gel for cleaning up the sample. After centrifugation, the upper layer was then evaporated to dryness with nitrogen, and dissolved with methanol, then injected into the GC–MS/MS system.</p><h3 data-test=\"abstract-sub-heading\">Results</h3><p>The coefficients of determination (r²) of constructed calibration curves were all greater than 0.999. The limits of detection for ropivacaine and 3-hydroxyropivacaine in target samples were 15 ng/mL and 10 ng/mL, respectively. The recovery rates of ropivacaine and 3-hydroxyropivacaine ranged from 97.6% to 103% and from 96.5% to 104%, respectively. The inter-day precision values of ropivacaine and 3-hydroxyropivacaine were not greater than 6.25% and 7.98%, respectively, and the inter-day trueness values were not greater than 6.90% and 8.33%, respectively; the intra-day precision and trueness values of ropivacaine and 3-hydroxyropivacaine were not greater than 3.20%, 6.78%, 7.84% and 8.99%, respectively.</p><h3 data-test=\"abstract-sub-heading\">Conclusions</h3><p>GC–MS/MS method for simultaneous detection and quantification of ropivacaine and 3-hydroxyropivacaine in biological samples was successfully developed. The method could also be applied to samples obtained from an authentic case; their distribution among tested fluids and solid tissues were also measured. This is the first report on the distribution of ropivacaine and its major metabolite 3-hydroxyropivacaine in a human case.</p>","PeriodicalId":12329,"journal":{"name":"Forensic Toxicology","volume":null,"pages":null},"PeriodicalIF":2.2,"publicationDate":"2024-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142269773","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":"Development of a simple estimation method of serum caffeine concentration using a point-of-care test kit for urinary caffeine.","authors":"Kenji Tsujikawa, Yuki Okada, Hiroki Segawa, Tadashi Yamamuro, Kenji Kuwayama, Tatsuyuki Kanamori, Yuko T Iwata","doi":"10.1007/s11419-024-00692-2","DOIUrl":"https://doi.org/10.1007/s11419-024-00692-2","url":null,"abstract":"<p><strong>Purpose: </strong>Serum caffeine concentration is an indicator of caffeine intoxication; however, it is difficult to measure it in most emergency departments. We developed a simple estimation method using a point-of-care test kit for urinary caffeine.</p><p><strong>Methods: </strong>Caffeine-spiked human serum (100, 50, 25, and 10 µg/mL) was diluted 10-, 20-, 50-, and 100-fold with phosphate-buffered saline and applied to the kit. After 5 min incubation, the kit was scanned by a flatbed scanner and the membrane image was processed with ImageJ.</p><p><strong>Results: </strong>When the 20-fold diluted serum was applied, serum samples with initial caffeine concentration ≤ 25 and ≥ 50 µg/mL were caffeine-negative and -positive, respectively. When the 100-fold diluted serum was applied, none of the caffeine-spiked serum samples gave positive results. Therefore, we proposed the following test procedure: (i) 20-fold diluted serum was initially tested and (ii) 100-fold diluted serum was additionally tested when the initial result was caffeine positive. Using this procedure, caffeine concentration is expected to be classified into three levels: ≤ 25, > 25- ≤ 100, and > 100 µg/mL, which almost correspond to no or mild, severe, and potentially fatal intoxication, respectively. The test procedure was validated using postmortem heart blood from two cases of fatal caffeine intoxication (caffeine concentration: 276 and 175 µg/mL) and two cases of other intoxication.</p><p><strong>Conclusions: </strong>Our developed method using point-of-care urinary caffeine test kits enabled simple estimation of serum caffeine concentration.</p>","PeriodicalId":12329,"journal":{"name":"Forensic Toxicology","volume":null,"pages":null},"PeriodicalIF":2.8,"publicationDate":"2024-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142072358","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":"Incorporation of suvorexant and lemborexant into hair and their distributions after a single intake.","authors":"Atsushi Nitta, Noriaki Shima, Hiroe Kamata, Misato Wada, Kengo Matsumoto, Hidenao Kakehashi, Shihoko Nakano-Fujii, Shuntaro Matsuta, Tooru Kamata, Munehiro Katagi, Takako Sato, Hiroshi Nishioka","doi":"10.1007/s11419-024-00700-5","DOIUrl":"https://doi.org/10.1007/s11419-024-00700-5","url":null,"abstract":"<p><strong>Purpose: </strong>This study examined the applicability of hair analysis as an approach to identify suvorexant (SUV) and lemborexant (LEM) intake by analyzing black hair specimens collected from study participants after a single oral administration.</p><p><strong>Methods: </strong>Hair specimens were collected form participants who took a single dose of 10 mg SUV or 5 mg LEM. Identification of the dual orexin receptor antagonists (DORAs) and their metabolites was performed by liquid chromatography-tandem mass spectrometry. Reference standards of S-M9 and L-M4, the metabolites of SUV and LEM, respectively, were synthesized in our laboratory. Sectional analysis of 1-mm segments of the single-hair strands was also performed to investigate the incorporation behavior of the drugs into hair.</p><p><strong>Results: </strong>Unchanged SUV and LEM, and their metabolites S-M9 and L-M4 were detected even in the single-hair specimens. Results of the segmental hair analysis showed predominant incorporation of the drugs into hair through the hair bulb region rather than through the upper dermis zone of the hair root. The drug concentrations in the hair specimens, collected about 1 month after intake, were 0.033-0.037 pg/hair strand (0.17-0.19 pg/mg) for SUV and 0.054-0.28 pg/hair strand (0.28-1.5 pg/mg) for LEM. The calculated distribution ratios of the DORAs into hair to the oral doses were much lower than those of benzodiazepines and zolpidem reported in a previous study.</p><p><strong>Conclusions: </strong>This is the first report of the detection of the DORAs in hair. The incorporation behavior of the DORAs into hair revealed herein are crucial for proper interpretation of hair test results.</p>","PeriodicalId":12329,"journal":{"name":"Forensic Toxicology","volume":null,"pages":null},"PeriodicalIF":2.8,"publicationDate":"2024-08-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141912378","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":"Effects of natural environments on drug contents in nails: comparison of drug residual rates between nails and hair to determine the drug-use history of corpses in unnatural death cases using micro-segmental analysis.","authors":"Kenji Kuwayama, Hajime Miyaguchi, Tatsuyuki Kanamori, Kenji Tsujikawa, Tadashi Yamamuro, Hiroki Segawa, Yuki Okada, Yuko T Iwata","doi":"10.1007/s11419-024-00701-4","DOIUrl":"https://doi.org/10.1007/s11419-024-00701-4","url":null,"abstract":"<p><strong>Purpose: </strong>We previously developed evaluation methods using micro-segmental analysis (MSA) to examine the effects of external environments on drug content in hair and nails. In this study, the effects of the natural environmental factors (water, temperature, humidity, light, and soil) on drug contents in nails were examined and compared with our previous experimental data on hair.</p><p><strong>Methods: </strong>Four hay-fever medicines were used as model drugs (fexofenadine, epinastine, cetirizine, and desloratadine) to evaluate drug stability in the nails. Reference nails containing the four medicines were collected from patients with hay fever who ingested the medicines daily for four months. The nails were exposed to various natural environments for up to four months.</p><p><strong>Results: </strong>The effects of temperature, humidity, and light on drug contents in the nails were comparatively small. Soil significantly decomposed the nail surfaces and decreased the drug content of the nails (up to 17 %). Water also decreased the drug content (up to 12 %), although no apparent changes in nail surfaces were observed.</p><p><strong>Conclusions: </strong>In comparison with hair data obtained under the same environmental conditions, light affected drugs in the hair rather than in nails, whereas water and soil greatly affected drugs in the nails rather than in hair. Although the disposition of drugs incorporated in the tissues differed between nails and hair, the analytes were detected in nails and hair strands left in severe natural environments. MSA could be useful for estimating drug-use histories and personal profiles using the nails and hair of a corpse.</p>","PeriodicalId":12329,"journal":{"name":"Forensic Toxicology","volume":null,"pages":null},"PeriodicalIF":2.8,"publicationDate":"2024-08-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141912376","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":"How to trace etomidate in illegal E-cigarettes from authentic human hair: identification, quantification and multiple-factor analysis.","authors":"Wanting Xie, Liying Zhou, Jinting Liu, Ziyi Li, Zehong Li, Wen Gao, Yan Shi","doi":"10.1007/s11419-024-00698-w","DOIUrl":"https://doi.org/10.1007/s11419-024-00698-w","url":null,"abstract":"<p><strong>Purpose: </strong>The abusive consumption of illegal E-cigarettes containing etomidate (ET) can have a significant impact on public mental and physical well-being. The purpose of this study is to establish a rapid quantitative method using ultra-high-performance liquid chromatography/tandem mass spectrometry (UHPLC-MS/MS) for the targeted screening of etomidate (ET) and its metabolite etomidate acid (ETA) in hair samples.</p><p><strong>Methods: </strong>A 1 mL methanol solution containing the internal standard ET-d₅ at a concentration of 50 pg/mg was added to 20 mg of hair and milled below 4 °C. After centrifugation, 5 μL of the supernatant was injected into a UHPLC-MS/MS system.</p><p><strong>Results: </strong>The limit of detection (LOD) and limit of quantification (LOQ) were determined to be 1 pg/mg and 10 pg/mg, respectively, for ET, and 10 pg/mg and 25 pg/mg, respectively, for ETA. Calibration curves for all analytes showed good linearity (r > 0.997), indicating a reliable method. Accuracies were between 92.12% and 110.72%. Intra-day and inter-day precision for all analytes at all concentration levels were below 10.13%. Analyte recoveries ranged from 86.90% to 101.43%, with a matrix effect ranging from -18.55% to -14.93%.</p><p><strong>Conclusions: </strong>The validated method was successfully used to analyze 105 hair samples from suspected ET users. Of these, 50 tested positive for ET and 43 tested positive for ETA above the LOQ. This demonstrates the effectiveness of the developed UHPLC-MS/MS method in detecting ET and ETA in hair samples, which could be instrumental in addressing the issue of illegal E-cigarette abuse and its impact on public health.</p>","PeriodicalId":12329,"journal":{"name":"Forensic Toxicology","volume":null,"pages":null},"PeriodicalIF":2.8,"publicationDate":"2024-08-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141912377","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":"In vivo assessment of the nephrotoxic effects of the synthetic cannabinoid AB-FUBINACA.","authors":"Ayman Alzu'bi, Ejlal Abu-El-Rub, Bahaa Al-Trad, Hiba Alzoubi, Hadeel Abu-El-Rub, Dima Albals, Gamal T Abdelhady, Noor S Bader, Rawan Almazari, Raed M Al-Zoubi","doi":"10.1007/s11419-024-00699-9","DOIUrl":"https://doi.org/10.1007/s11419-024-00699-9","url":null,"abstract":"<p><strong>Background: </strong>The widespread misuse of synthetic cannabinoids (SCs) has led to a notable increase in reported adverse effects, raising significant health concerns. SCs use has been particularly associated with acute kidney injury (AKI). However, the pathogenesis of SCs-induced AKI is not well-understood.</p><p><strong>Methods: </strong>We investigated the nephrotoxic effect of acute administration of N-[(1S)- 1-(aminocarbonyl)-2-methylpropyl]-1-[(4-fluorophenyl)methyl]-1H-indazole-3-carboxamide (AB-FUBINKA) (3 mg/kg for 5 days) in mice. Various parameters of oxidative stress, inflammation, and apoptosis have been quantified. The expressions of mitochondrial complexes (I-V) in renal tissues were also assessed.</p><p><strong>Results: </strong>Our findings showed that AB-FUBINACA induced substantial impairment in the renal function that is accompanied by elevated expression of renal tubular damage markers; KIM-1 and NGAL. Administration of AB-FUBINACA was found to be associated with a significant increase in the expression of oxidative stress markers (iNOS, NOX4, NOX2, NOS3) and the level of lipid peroxidation in the kidney. The expression of pro-inflammatory markers (IL-6, TNF-alpha, NF-kB) was also enhanced following exposure to AB-FUBINACA. These findings were also correlated with increased expression of major apoptosis regulatory markers (Bax, caspase-9, caspase-3) and reduced expression of mitochondrial complexes I, III, and IV.</p><p><strong>Conclusion: </strong>These results indicate that AB-FUBINACA can trigger oxidative stress and inflammation, and activate caspase-dependent apoptosis in the kidney, with these processes being possibly linked to disruption of mitochondrial complexes and could be an underlying mechanism of SCs-induced nephrotoxicity.</p>","PeriodicalId":12329,"journal":{"name":"Forensic Toxicology","volume":null,"pages":null},"PeriodicalIF":2.8,"publicationDate":"2024-08-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141906325","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":"Silymarin ameliorates diazinon-induced subacute nephrotoxicity in rats via the Keap1-Nrf2/heme oxygenase-1 signaling pathway.","authors":"Eman Mohamed Fath, Hatem H Bakery, Ragab M El-Shawarby, Mohamed E S Abosalem, Samar S Ibrahim, Nesrine Ebrahim, Ahmed Medhat Hegazy","doi":"10.1007/s11419-024-00697-x","DOIUrl":"https://doi.org/10.1007/s11419-024-00697-x","url":null,"abstract":"<p><strong>Purpose: </strong>The goal of the current study was to clarify the potential molecular mechanism underlying the protective effects of silymarin (SIL) administration against diazinon-induced subacute nephrotoxicity, with a special emphasis on the role of the Kelch-like-associated protein-1 (Keap1)-nuclear factor erythroid 2-related factor 2 (Nrf2)-heme oxygenase-1 (HO-1) signaling pathway in minimizing the oxidative stress induced by diazinon (DZN).</p><p><strong>Methods: </strong>Five equal groups of thirty adult male Wistar rats were created at random. Group 1 (G1) was maintained under typical control conditions and administered saline intragastrically (I/G) once daily for 4 weeks; G2 was administered olive oil I/G for 4 weeks; G3 was I/G administered silymarin daily for 4 weeks; G4 was I/G administered diazinon daily for 4 weeks. G5 was I/G administered silymarin daily 1 h before the I/G administration of the diazinon for 4 weeks. Blood samples were collected at the end of the experiment for the determination of complete blood cell count, and kidney function tests. Kidney specimens were collected for the evaluation of the oxidative markers, mRNA gene expression, protein markers, and histopathological examination.</p><p><strong>Results: </strong>SIL reduced the renal dysfunction caused by DZN by restoring urea and creatinine levels, as well as oxidative indicators. Although the expression of Keap-1 was also elevated, overexpression of Nrf2 also enhanced the expression of HO-1, a crucial target enzyme of Nrf2.</p><p><strong>Conclusions: </strong>SIL is hypothesized to potentially aid in the prevention and management of nephrotoxicity caused by DZN.</p>","PeriodicalId":12329,"journal":{"name":"Forensic Toxicology","volume":null,"pages":null},"PeriodicalIF":2.8,"publicationDate":"2024-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141906326","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}