Drug and Chemical Toxicology最新文献

{"title":"Toxicological evaluation of LivLonga^®, a polyherbal combination, in rodents.","authors":"Anju Majeed, Anjali Pandey, Smitha Thazhathidath, Sarang Bani","doi":"10.1080/01480545.2024.2420729","DOIUrl":"https://doi.org/10.1080/01480545.2024.2420729","url":null,"abstract":"<p><p>There has been keen interest on herbs and phytoconstituents with hepatoprotective property to help restore healthy liver function. Ayurveda, the ancient Indian traditional system of medicine mentions about <i>Curcuma longa</i>, <i>Garcinia indica</i> and <i>Piper nigrum</i> which are reported to have hepatoprotective activity. Apart from supporting metabolism, liver plays pivotal role in numerous bodily processes, immune functions to digestion, detoxification, and storage of nutrients. Factors such as sedentary lifestyle, viral infections, drugs/chemicals, high calorie diet, excess intake of alcohol etc have adverse impact on normal functioning of liver. Development of novel herbal combination with standards of safety and efficacy can help manage liver ailments and protect liver health. LivLonga^® is a polyherbal combination of scientifically validated ingredients- curcuminoids, garcinol and piperine to support healthy liver function. The present work was conducted to evaluate toxicity of LivLonga^® using <i>in vivo</i> models when administered orally. The acute, subacute, and subchronic toxicity studies were carried out in accordance with the test guidelines established by the Organization for Economic Cooperation and Development. A single-dose acute oral toxicity produced no toxic effects after 14 days of treatment. Four-week (subacute) and 3-months (subchronic) oral toxicity studies were conducted and observed no abnormal clinical signs, no alterations in the body weight, hematology and biochemical parameters or gross and histopathological changes. Thus, oral administration of LivLonga^® showed no signs of toxicity when dosed orally to rats, with a no observed adverse effect level (NOAEL) of 600 mg/kg/day.</p>","PeriodicalId":11333,"journal":{"name":"Drug and Chemical Toxicology","volume":" ","pages":"1-14"},"PeriodicalIF":2.1,"publicationDate":"2024-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142582192","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":"The nephroprotective effect of Quercetin in Cyclophosphamide-induced renal toxicity might be associated with MAPK/ERK and NF-κB signal modulation activity.","authors":"Ugur Seker, Deniz Evrim Kavak, Fatma Zehra Dokumaci, Sefa Kizildag, Sevgi Irtegun-Kandemir","doi":"10.1080/01480545.2024.2347541","DOIUrl":"10.1080/01480545.2024.2347541","url":null,"abstract":"<p><p>The present study aimed to examine the protective effect of quercetin (QUE) on cyclophosphamide (CTX)-induced nephrotoxicity. For that purpose, 24 mice were divided into four groups (Control, QUE, CTX, and CTX + QUE). The CTX and CTX + QUE groups received 200 mg/kg of cyclophosphamide on the 1^st and 7^th days. The QUE and CTX + QUE groups were treated with 50 mg/kg of quercetin daily for 14 days. At the end of the experiment, the animals were sacrificed, and kidney samples were analyzed. The results indicated that CTX leads to severe morphological degenerations and disruption in renal function. Serum BUN, Creatinine, Uric acid, tissue Bax, Caspase 3, TNF-α and IL-1β expression levels were upregulated in the CTX group compared to Control and QUE groups (<i>p</i> < 0.05). Although MAPK/ERK phosphorylation level is not affected in CTX group, there was a significant increase in CTX + QUE group (<i>p</i> < 0.05), but the NF-κB was significantly suppressed in this group (<i>p</i> < 0.01). The RT-qPCR results showed that the cyt-c and the Bax/Bcl-2 ratio mRNA expression folds were upregulated in the CTX group (<i>p</i> < 0.01), which was downregulated in the CTX + QUE group. However, there was a significant difference in the CTX + QUE group compared to the Control and QUE groups (<i>p</i> < 0.01). The findings showed that administering quercetin along with cyclophosphamide alleviated renal injury by regulating apoptotic and inflammatory expression. Moreover, the administration of quercetin and cyclophosphamide could synergistically improve renal function test results, and activate cellular responses, which upmodulate MAPK/ERK phosphorylation and suppression of NF-κB.</p>","PeriodicalId":11333,"journal":{"name":"Drug and Chemical Toxicology","volume":" ","pages":"1165-1174"},"PeriodicalIF":2.1,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140897782","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":"Investigation of the role of K_ATP channels in the cytotoxic effect of cypermethrin on rat-derived aortic smooth muscle cells.","authors":"Fatma Söğüt, Coşar Uzun, Deniz Kibar, Ülkü Çömelekoğlu","doi":"10.1080/01480545.2024.2352082","DOIUrl":"10.1080/01480545.2024.2352082","url":null,"abstract":"<p><p>We investigate role of ATP sensitive potassium (K_ATP) channel in cytotoxic effect of cypermethrin on rat aortic smooth muscle cells. Cytotoxicity analysis was performed at 0, 0.1, 0.5, 10, 50, and 100 µM concentrations of cypermethrin and the cell index (CI) was calculated. K_ATP currents were recorded using patch clamp technique for 50 and 100 µM concentrations and channel conductivity was determined by obtaining current-voltage characteristics. No cytotoxic effect was observed in the first 72 hours. At the 96th hour, only at 100 µM concentration, the CI value decreased significantly compared to control group and at 120 and 144th hours, it was observed that the CI value decreased significantly at all concentrations. Currents and conductivities were significantly decreased at 50 and 100 µM concentrations. Results gave clues that cypermethrin causes a cytotoxic effect on vascular smooth muscles and that K_ATP channels may have a role in the emergence of this effect.</p>","PeriodicalId":11333,"journal":{"name":"Drug and Chemical Toxicology","volume":" ","pages":"1218-1225"},"PeriodicalIF":2.1,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140921519","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":"New oxomethacrylate and acetamide: synthesis, characterization, and their computational approaches: molecular docking, molecular dynamics, and ADME analyses.","authors":"Verda Çoban, Nevin Çankaya, Serap Yalçın Azarkan","doi":"10.1080/01480545.2024.2349651","DOIUrl":"10.1080/01480545.2024.2349651","url":null,"abstract":"<p><p>The compounds 2-chloro-N-(3-methoxyphenyl)acetamide (m-acetamide) and 2-(3-methoxyphenylamino)-2-oxoethyl methacrylate (3MPAEMA) were synthesized in this study for the first time in the literature. FTIR, ¹H, and ¹³C NMR spectroscopic techniques were used to characterize it. Subsequently, computational techniques were used to assess various ADME factors, such as drug-likeness properties, bioavailability score, and adherence to Lipinski's rule. Finally, molecular docking experiments were conducted with the human topoisomerase α2 (TOP2A) protein to verify and validate the reliability and stability of the docking procedure. The results of the docking scores, which quantify binding affinity, indicated that these derivatives exhibited a stronger affinity for TOP2A.</p>","PeriodicalId":11333,"journal":{"name":"Drug and Chemical Toxicology","volume":" ","pages":"1175-1184"},"PeriodicalIF":2.1,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140921526","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":"Neuroprotective potential of solanesol against tramadol induced zebrafish model of Parkinson's disease: insights from neurobehavioral, molecular, and neurochemical evidence.","authors":"Md Reyaz Alam, Vaishali Dobhal, Shamsher Singh","doi":"10.1080/01480545.2024.2355542","DOIUrl":"10.1080/01480545.2024.2355542","url":null,"abstract":"<p><p>Parkinson's disease (PD) is a prevalent neurodegenerative disorder characterized by the loss of dopaminergic neurons in the substantia nigra pars compacta (SNpc) and subsequent depletion of dopamine in the striatum. Solanesol, an alcohol that acts as a precursor to coenzyme Q10, possesses potential applications in managing neurological disorders with antioxidant, anti-inflammatory, and neuromodulatory potential. In this study, a zebrafish model was employed to investigate the effects of solanesol in tramadol induced PD like symptoms. Zebrafish were administered tramadol injections (50 mg/kg) over a 20-day period. Solanesol was administered at doses of 25, 50, and 100 mg/kg, three hours prior to tramadol administration from day 11 to day 20. Behavioral tests assessing motor coordination were conducted on a weekly basis using open field and novel diving tank apparatus. On day 21, the zebrafish were euthanized, and brain tissues were examined for markers of oxidative stress, inflammation, and neurotransmitters level. Chronic tramadol treatment resulted in motor impairment, reduced antioxidant enzyme levels, enhanced release of proinflammatory cytokines in the striatum, and disrupted neurotransmitter balance. However, solanesol administration mitigated these effects and exhibited a neuroprotective effect against neurodegenerative alterations in the zebrafish model of PD. This was evident through improvements in behavior, modulation of biochemical markers, attenuation of neuroinflammation, restoration of neurotransmitters level, and enhancement of mitochondrial activity. The histopathological study also confirmed that solanesol dose dependently restored neuronal cell density which confirmed its neuroprotective potential. Further investigations are required to elucidate the underlying mechanisms of solanesol neuroprotective effects and evaluate its efficacy in human patients.</p>","PeriodicalId":11333,"journal":{"name":"Drug and Chemical Toxicology","volume":" ","pages":"1241-1256"},"PeriodicalIF":2.1,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141466897","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":"Livogrit prevents Amiodarone-induced toxicity in experimental model of human liver (HepG2) cells and <i>Caenorhabditis elegans</i> by regulating redox homeostasis.","authors":"Acharya Balkrishna, Vivek Gohel, Nishit Pathak, Kunal Bhattacharya, Rishabh Dev, Anurag Varshney","doi":"10.1080/01480545.2024.2320189","DOIUrl":"10.1080/01480545.2024.2320189","url":null,"abstract":"<p><p>Treatment with cationic amphiphilic drugs like Amiodarone leads to development of phospholipidosis, a type of lysosomal storage disorder characterized by excessive deposition of phospholipids. Such disorder in liver enhances accumulation of drugs and its metabolites, and dysregulates lipid profiles, which subsequently leads to hepatotoxicity. In the present study, we assessed pharmacological effects of herbal medicine, Livogrit, against hepatic phospholipidosis-induced toxicity. Human liver (HepG2) cells and <i>in vivo</i> model of <i>Caenorhabditis elegans</i> (N2 and CF1553 strains) were used to study effect of Livogrit on Amiodarone-induced phospholipidosis. In HepG2 cells, Livogrit treatment displayed enhanced uptake of acidic pH-based stains and reduced phospholipid accumulation, oxidative stress, AST, ALT, cholesterol levels, and gene expression of SCD-1 and LSS. Protein levels of LPLA2 were also normalized. Livogrit treatment restored Pgp functionality which led to decreased cellular accumulation of Amiodarone as observed by UHPLC analysis. In <i>C. elegans</i>, Livogrit prevented ROS generation, fat-6/7 gene overexpression, and lysosomal trapping of Amiodarone in N2 strain. SOD-3::GFP expression in CF1553 strain normalized by Livogrit treatment. Livogrit regulates phospholipidosis by regulation of redox homeostasis, phospholipid anabolism, and Pgp functionality hindered by lysosomal trapping of Amiodarone. Livogrit could be a potential therapeutic intervention for amelioration of drug-induced phospholipidosis and prevent hepatotoxicity.</p>","PeriodicalId":11333,"journal":{"name":"Drug and Chemical Toxicology","volume":" ","pages":"987-1003"},"PeriodicalIF":2.1,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139995865","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":"Investigating the impact of external application of formalin and potassium permanganate on hematological, immunological, and biochemical profiles in <i>Labeo rohita</i> fingerlings.","authors":"Lukesh Kumar Banjare, Himadri Saha, Arpit Acharya, Md Idrish Raja Khan","doi":"10.1080/01480545.2024.2318654","DOIUrl":"10.1080/01480545.2024.2318654","url":null,"abstract":"<p><p>The present study aimed to elucidate the suitability of formalin and KMnO₄ as therapeutics for fish diseases in Indian major carp, <i>Labeo rohita</i>, while considering their impact on fish stress levels. Acute toxicity tests revealed that the 96-hour LC₅₀ values for formalin and KMnO₄ were 66.58 ppm and 2.89 ppm, respectively. Sub-lethal concentrations of formalin (6.65 ppm, 3.32 ppm, and 2.21 ppm) and KMnO₄ (0.289 ppm, 0.145 ppm, and 0.096 ppm), along with control groups, were administered to the fish for different exposure periods (24, 48, 72, and 96 hours) and different hematological, biochemical, and immunological parameters were analyzed. The findings demonstrated that formalin exposure resulted in a significant decrease (<i>p</i> < 0.05) in hematological parameters, immunological parameters, and serum protein levels. Conversely, formalin exposure led to significant increases (<i>p</i> < 0.05) in serum glucose, SGOT, SGPT, and ALP levels. In contrast, KMnO₄ exposure significantly decreased (<i>p</i> < 0.05) hematological parameters and serum protein levels, while significantly increasing (<i>p</i> < 0.05) immunological parameters. To evaluate curative efficacy, challenge studies were conducted using three sub-lethal concentrations of formalin and KMnO₄ against <i>Aeromonas hydrophila</i> (ATCC 7966) infection. Based on the aforementioned results, the recommended doses of formalin and KMnO₄ were found to be 6.65 ppm and 0.289 ppm, respectively.</p>","PeriodicalId":11333,"journal":{"name":"Drug and Chemical Toxicology","volume":" ","pages":"974-986"},"PeriodicalIF":2.1,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140174083","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":"Pre-clinical and cellular safety assessment of oral administered DHA rich microalgae oil from <i>Schizochytrium</i> sp. (Strain ATCC-20889): acute, sub-chronic and genotoxicity.","authors":"Shubham Thakur, Harmanpreet Singh, Sunil Sharma, Manjot Kaur, Amrinder Singh, Arvinder Kaur, Subheet Kumar Jain","doi":"10.1080/01480545.2024.2308835","DOIUrl":"10.1080/01480545.2024.2308835","url":null,"abstract":"<p><p>The lack of toxicity data for DHA-rich oil from <i>Schizochytrium</i> sp. (Strain ATCC-20889) leads to its exclusion from the Qualified Presumption of Safety list. Therefore, present study addresses toxicity evaluation of DHA-rich microalgae oil using <i>ex-vivo</i> (cytotoxicity assay) and <i>in-vivo</i> methods (acute (OECD 423 guidelines), sub-chronic (OECD 452 guidelines), and genotoxicity assay). The <i>ex-vivo</i> results showed >90% cell viability of Caco-2 cells after 48 h of treatment (200 µg/mL of DHA). Additionally, the <i>in-vivo</i> acute toxicity study found that microalgae oil was nontoxic and classified under category 5 molecule according to OECD 423 guidelines with a highest degree of safety at 2000 mg/kg b.w. The <i>in-vivo</i> sub-chronic study revealed no significant mortality and changes in feed intake, body weight, haematological, biochemical, neurological, and urine parameters after repeated 180-days administration of DHA-rich microalgae oil at 250 mg/kg, 500 mg/kg, and 1000 mg/kg. Moreover, histopathology evaluation, comet assay, chromosomal aberration, and micronuclei assay also confirmed the nontoxic behavior of DHA-rich oil. Thus, the results from the <i>ex-vivo</i> and <i>in-vivo</i> studies indicate that DHA-rich oil from <i>Schizochytrium</i> sp. (Strain ATCC-20889) is safe for use as a novel food, and can be included in infants, adults, pregnant women, and children formula.</p>","PeriodicalId":11333,"journal":{"name":"Drug and Chemical Toxicology","volume":" ","pages":"876-888"},"PeriodicalIF":2.1,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139680891","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":"Testing the detoxification power of black cumin oil (<i>Nigella sativa</i>) over cypermethrin insecticide effects in rainbow trout (<i>Oncorhynchus mykiss</i>) at multiple scales.","authors":"Veysel Karani Gültekin, Muhammed Atamanalp, Arzu Ucar, Gonca Alak, Veysel Parlak","doi":"10.1080/01480545.2024.2311279","DOIUrl":"10.1080/01480545.2024.2311279","url":null,"abstract":"<p><p>This study investigated the curative effect of black cumin oil (<i>Nigella sativa</i>, NS), which is a phytotherapeutic agent against to cypermethrin (CYP), which is known to have adverse effects on rainbow trout (<i>Oncorhynchus mykiss</i>)'s behavioral changes, oxidative stress-mediated neurotoxicity, hematotoxicity and hepatotoxicity parameters.At the end of the trial period; (i) evaluation of critical swimming speed (U_crit) (ii) hematology indices [white blood cell (WBC), red blood cell (RBC), hemoglobin (Hgb), hematocrit (Hct), mean cell volume (MCV), mean cell hemoglobin) (MCH), mean cell hemoglobin concentration (MCHC)] (iii) Elucidation of the mechanism of functional damage in brain tissue of <i>O. mykiss</i> by neurological parameter [acetylcholinesterase (AChE)] (iv) Evaluation of oxidative damage in oxidative stress-mediated neurotoxicity and hepatotoxicity in liver, gill and brain tissue of <i>O. mykiss</i> with antioxidant enzymes [(Superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), Glutathione (GSH)] and [(detection by means of malondialdehyde (MDA)] (v) Obtaining applicable data in the toxicological field using a multi-biomarker approach to investigate the modulation of NS administration via target markers in the physiological pathway of <i>O. mykiss</i> were aimed.As a result of CYP application, it was determined that the Ucrit value of <i>O. mykiss</i> decreased significantly. It was determined that the changes in the values of RBC, Hgb and Hct, which are among the hematology parameters examined in the blood tissue, were statistically significant (<i>p</i> < 0.05). It was determined that WBC value was inhibited by CYP application and NS tried to make a positive contribution to WBC. It was determined that the AChE activity of <i>O. mykiss</i> in the brain tissue had a statistically significant inhibition in the CYP-treated group (<i>p</i> < 0.05). SOD, CAT, GPx, enzyme activities were found to be inhibited by CYP application and were statistically significant (<i>p</i> < 0.05). Acute toxicity of CYP was determined by antioxidant enzyme biomarkers in gill tissue. In the results obtained; While inhibitions were determined in SOD, CAT, GPx activities compared to the control group, an induction occurred in MDA value.NS administration was noted to be an important modulator of the SOD-CAT system against CYP exposure at both concentrations. Thus, it can be said that it indirectly functions as an effective antioxidant through the NS receptor protein and structurally stimulates the synthesis and activity of antioxidative enzymes under oxidative stress.</p>","PeriodicalId":11333,"journal":{"name":"Drug and Chemical Toxicology","volume":" ","pages":"909-922"},"PeriodicalIF":2.1,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139702080","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":"Acute exposure of zebrafish (<i>Danio rerio</i>) adults to <i>psychotria carthagenensis</i> leaf extracts: chemical profile, lack of genotoxicity and histological changes.","authors":"Giovana Coutinho Zulin Nascimento, Rosemary Matias, Ana Luisa Miranda-Vilela, Katyuce Souza Farias, Denise Brentan Silva, Gilberto Gonçalves Facco, Mirra Angelina Neres da Silva, Carla Letícia Gediel Rivero-Wendt","doi":"10.1080/01480545.2024.2367560","DOIUrl":"10.1080/01480545.2024.2367560","url":null,"abstract":"<p><p><i>Psychotria carthagenensis</i> is a shrubby plant, often consumed by traditional populations in religious rituals. Previous studies have shown that this plant's infusion can inhibit the activity of Acetylcholinesterase (AChE) in rats. Despite the therapeutic potential, there is a lack of research regarding its possible toxicological and genotoxic effects. Hence, this study aimed to analyze the chemical profile of the ethanol extract from <i>P. carthagenensis</i> leaves by LC-DAD-MS and assess its possible toxicity and genotoxicity in zebrafish (<i>Danio rerio</i>). Adult zebrafish (N = 9/group) were exposed at different concentrations and the LC₅₀ was calculated. Frequencies of micronucleus (MN) and nuclear abnormalities (NA) were estimated for genotoxic effects, and degree of tissue changes (DTC) was used to assess the liver and gill histopathology. From the LC-DAD-MS analyses, the identified compounds included <i>N</i>-fructosyl valine, ethyl hexoside, 5-<i>O-E</i>-caffeoylquinic acid, <i>N-</i>feruloylagmatime, roseoside, di-O-deoxyhexoyl-hexosyl quercetin, loiolide, and oleamide. The calculated values of LC₅₀ did not vary significantly during the time of exposure. At the concentrations of 1.25, 2.5, 3.75, 5, 7.5, 10 and 15 mg/L, there was no genotoxicity, and only low to moderate toxicity for the tissues was observed, despite mortality of 100% at doses of 20-100 mg/L of <i>P. carthagenensis</i> ethanolic leaf extract. There were changes in cytoplasm of hepatocytes at 1.25 mg/L, and karyorrhexis, karyolysis and megalocytosis at 10 mg/L. In the gills, the alterations were primary lamellar hyperplasia in all concentrations, and at 10 mg/L, secondary lamellar edema and vascular hyperemia were common. Additionally, the chemical composition of <i>P. carthagenensis</i> was expanded.</p>","PeriodicalId":11333,"journal":{"name":"Drug and Chemical Toxicology","volume":" ","pages":"1358-1368"},"PeriodicalIF":2.1,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141476181","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}