Journal of Toxicology最新文献

{"title":"Paclitaxel Induces Neurotoxicity by Disrupting Tricarboxylic Acid Cycle Metabolic Balance in the Mouse Hippocampus.","authors":"Xi Liu,&nbsp;Changmeng Cui,&nbsp;Wenxue Sun,&nbsp;Junjun Meng,&nbsp;Jinxiu Guo,&nbsp;Linlin Wu,&nbsp;Beibei Chen,&nbsp;Dehua Liao,&nbsp;Pei Jiang","doi":"10.1155/2023/5660481","DOIUrl":"https://doi.org/10.1155/2023/5660481","url":null,"abstract":"<p><strong>Objective: </strong>It is well known that paclitaxel (PTX)-induced neurotoxicity seriously affects the quality of life of patients and is the main reason for reducing the dose of chemotherapy or even stopping chemotherapy. The current data are limited, and further information is required for practice and verification. The aims of this study were to clarify the molecular mechanism underlying PTX-induced neurotoxicity by combining <i>in vivo</i> and <i>in vitro</i> metabolomics studies and provide new targets for the prevention and treatment of PTX-induced neurotoxicity.</p><p><strong>Methods: </strong>In the <i>in vivo</i> study, a PTX-induced neurotoxicity mouse model was established by intraperitoneal injection of PTX (6 mg/kg every three days) for two consecutive weeks. After verification by water maze tests and HE staining of pathological sections, hippocampal metabolites were measured and the differential metabolites and related metabolic pathways were identified by multivariate statistical analysis. In the <i>in vitro</i> study, we investigated the effects of PTX on mouse hippocampal neuron cells, assessing the concentration and time of administration by MTT assays. After modeling, the relevant metabolites in the TCA cycle were quantified by targeted metabolomics using stable isotope labeling. Finally, the key enzymes of the TCA cycle in tissues and cells were verified by RT-PCR.</p><p><strong>Results: </strong>Administration of PTX to model mice resulted in neurological damage, shown by both water-maze tests and hippocampal tissue sections. Twenty-four metabolites and five associated metabolic pathways were found to differ significantly between the hippocampal tissues of the model and control groups. These included metabolites and pathways related to the TCA cycle and pyruvate metabolism. Metabolomics analysis using stable isotope labeling showed significant changes in metabolites associated with the TCA cycle compared with the control group (<i>P</i> < 0.05). Finally, RT-PCR verified that the expression of key enzymes in the TCA cycle was changed to different degrees in both hippocampal tissues and cells.</p><p><strong>Conclusion: </strong>Our results showed that PTX neurotoxicity in hippocampal tissue and neuron cells was associated with inhibition of the TCA cycle. This inhibition leads to brain insufficiency and impaired metabolism, resulting in various neurotoxic symptoms.</p>","PeriodicalId":17421,"journal":{"name":"Journal of Toxicology","volume":"2023 ","pages":"5660481"},"PeriodicalIF":2.9,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10423086/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9998197","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Polycyclic Aromatic Hydrocarbons in Soil and Vegetation of Niger Delta, Nigeria: Ecological Risk Assessment.","authors":"Esther Amaka Okoye,&nbsp;Anthonet N Ezejiofor,&nbsp;Ify L Nwaogazie,&nbsp;Chiara Frazzoli,&nbsp;Orish E Orisakwe","doi":"10.1155/2023/8036893","DOIUrl":"https://doi.org/10.1155/2023/8036893","url":null,"abstract":"<p><p>The Niger Delta, Nigeria, is noted for crude oil exploration. Whereas there seems to be a handful of data on soil polycyclic aromatic hydrocarbon (PAH) levels in this area, there is a paucity of studies that have evaluated soil and vegetation PAHs simultaneously. The present study has addressed this information gap. Fresh <i>Panicum maximum</i> (Jacq) (guinea grass), <i>Pennisetum purpureum</i> Schumach (elephant grass), <i>Zea mays</i> (L.) (maize), and soil samples were collected in triplicate from Choba, Khana, Trans-Amadi, Eleme, Uyo, and Yenagoa. PAHs determination was carried out using GC-MS. The percentage composition of the molecular weight distribution of PAHs, the molecular ratio of selected PAHs for identification of possible sources, and the isomeric ratio and total index of soil were evaluated. <i>Pennisetum purpureum</i> Schumach (elephant grass) from Uyo has the highest (10.0 mg·kg^-1) PAH while <i>Panicum maximum</i> (Jacq) (guinea grass) has the highest PAH (32.5 mg·kg^-1 from Khana. <i>Zea mays</i> (L.) (maize) from Uyo (46.04%), <i>Pennisetum purpureum</i> Schumach (elephant grass) from Trans-Amadi (47.7%), guinea grass from Eleme (49.2%), and elephant grass from Choba (39.9%) contained the highest percentage of high molecular weight (HMW) PAHs. Soil samples from Yenagoa (53.5%) and Khana (55.3%) showed the highest percentage of HMW PAHs. The total index ranged 0.27-12.4 in Uyo, 0.29-8.69 in Choba, 0.02-10.1 in Khana, 0.01-5.53 in Yenagoa, 0.21-9.52 in Eleme, and 0.13-8.96 in Trans-Amadi. The presence of HMW PAHs and molecular diagnostic ratios suggest PAH pollution from pyrogenic and petrogenic sources. Some soils in the Niger Delta show RQ_(NCs) values higher than 800 and require remediation to forestall ecohealth consequences.</p>","PeriodicalId":17421,"journal":{"name":"Journal of Toxicology","volume":"2023 ","pages":"8036893"},"PeriodicalIF":2.9,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10374382/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9912038","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Evaluating the Impact of Commonly Used Pesticides on Honeybees (<i>Apis mellifera</i>) in North Gonder of Amhara Region, Ethiopia.","authors":"Zewdie Abay,&nbsp;Amssalu Bezabeh,&nbsp;Alemayehu Gela,&nbsp;Asaminew Tassew","doi":"10.1155/2023/2634158","DOIUrl":"https://doi.org/10.1155/2023/2634158","url":null,"abstract":"<p><p>Global honeybee losses and colony decline are becoming continuous threat to the apicultural industry, as well as, for food security and environmental stability. Although the putative causes are still unclear, extensive exposure of bees to pesticides could be the possible factor for worldwide colony losses. This study was aimed at evaluating the impact of nine commonly used pesticide incidents on adult worker honeybees (<i>A. mellifera</i>) under the laboratory condition, in North Gonder of Amhara region, Ethiopia. Feeding test, contact test, and fumigation tests were carried out for each pesticide following the standard procedures, and each pesticide toxicity was compared to the standard toxic chemical, dimethoate 40% EC (positive control), and to 50% honey solution (negative control). The results revealed that all the tested pesticides caused significant deaths of the experimental bees (<i>P</i> < 0.05) in all the tests when compared to the negative control. Diazinon 60% EC, endosulfan 35% EC, and malathion 50% EC were appeared highly toxic causing 100% mortality of bees, while chlorsulfuron 75% WG killed 90% of the experimental bees as tested via feeding. On the other hand, agro-2, 4-D and its mixture with glycel 41% EC are moderately toxic, and mancozeb 80% WP and glycel 41% EC were slightly toxic to honeybees as compared to the positive control (dimethoate 40% EC). Suddenly, diazinon 60% EC and malathion 50% EC triggered 100% mortality of bees, while endosulfan 35% EC and chlorsulfuron 75% WG caused 63.63% and 90.82% of bee mortality, respectively, when evaluated via contact test. The fumigation test also showed that chlorsulfuron 75% WG, diazinon 60% EC, and endosulfan 35% EC caused 100%, 86.7%, and 65.6% mortality rate of bees. Our result also highlighted that tested LD₅₀ of all pesticide incidents were significantly lower than the manufacturer-based LD_50. This shows that local honeybees <i>A. m. jemenetica</i> are extremely sensitive to commonly used agricultural pesticides, which may affect the colony level due to the intensive application of these pesticides in Ethiopia.</p>","PeriodicalId":17421,"journal":{"name":"Journal of Toxicology","volume":"2023 ","pages":"2634158"},"PeriodicalIF":2.9,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10081893/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9336683","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Acute and Subchronic Oral Toxicity Evaluation of Herbal Formulation: <i>Piper crocatum</i> Ruiz and Pav., <i>Typhonium flagelliforme</i> (Lodd.) Blume, and <i>Phyllanthus niruri</i> L. in Sprague-Dawley Rats.","authors":"Retno Murwanti,&nbsp;A Nurrochmad,&nbsp;Andayana P Gani,&nbsp;Ediati Sasmito,&nbsp;Angela E Edwina,&nbsp;Mayang K Chandra,&nbsp;F H Suryawan,&nbsp;A R Wardana,&nbsp;Natalia,&nbsp;Jelita L S R Budiningsih","doi":"10.1155/2023/7511397","DOIUrl":"https://doi.org/10.1155/2023/7511397","url":null,"abstract":"<p><strong>Background: </strong>The product combination of <i>Piper crocatum</i> Ruiz. and Pav., <i>Phyllanthus niruri</i> Linn., and <i>Typhonium flagelliforme</i> (Lodd.) BL ethanolic extract (SKM) exerts immunomodulatory activity. However, the toxicity profile of the combination has never been investigated.</p><p><strong>Objective: </strong>This study aimed to establish the acute toxicity profile of the SKM product on Sprague-Dawley (SD) rats and its subchronic toxicity profile on female SD rats.</p><p><strong>Method: </strong>The acute and subchronic toxicity tests were conducted in accordance with OECD 423 and OECD 408, respectively.</p><p><strong>Result: </strong>The SKM product was safe up to 5000 mg/kg b.w. in male and female SD rats. In repeated doses of SKM for 90 days, the administration of 22.5, 45, and 90 mg/kg b.w. per day of the SKM product to female SD rats did not affect clinical signs, body weight, food and water consumption, hematological parameters, clinical chemical parameters, urinalysis, relative organ weights, and gross pathological and histopathological features compared with the control group.</p><p><strong>Conclusion: </strong>Analyses of these results suggest that the long-term oral administration of the SKM product for 90 days does not cause subchronic toxicity.</p>","PeriodicalId":17421,"journal":{"name":"Journal of Toxicology","volume":"2023 ","pages":"7511397"},"PeriodicalIF":2.9,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9831695/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10527550","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Zinc Chloride Can Mitigate the Alterations in Metallothionein and Some Apoptotic Proteins Induced by Cadmium Chloride in Mice Hepatocytes: A Histological and Immunohistochemical Study.","authors":"Enas Nihad Bayram,&nbsp;Nahla A Al-Bakri,&nbsp;Hanady S Al-Shmgani","doi":"10.1155/2023/2200539","DOIUrl":"https://doi.org/10.1155/2023/2200539","url":null,"abstract":"<p><p>The heavy metal cadmium is extremely harmful to both humans and animals. Zinc supplementation protects the biological system and reduces cadmium-induced toxicity. This study aimed to determine whether zinc chloride (ZnCl₂) could protect male mice with the damaged liver induced by cadmium chloride (CdCl₂). The protective role of zinc chloride and expression of the metallothionein (MT), Ki-67, and Bcl-2 apoptotic proteins in hepatocytes were studied after subchronic exposure of mice to cadmium chloride for 21 days. Thirty male mice were randomly categorized into 6 groups (5 mice/group) as follows: a control group that did not receive any treatment, a group given ZnCl₂ at 10 mg/kg alone, and two groups received ZnCl₂ (10 mg/kg) in combination with CdCl₂ at two concentrations (1.5 and 3 mg/kg), while the last two groups received CdCl₂ alone at 1.5 and 3 mg/kg, respectively. Immunohistochemical examination revealed a decrease in Ki-67 expression in Kupffer and endothelial cells, which reflected cell proliferation downregulation accompanied by MT increased expression. However, the Bcl-2 was ameliorated and reduced to demonstrate an enhanced rate of necrosis rather than apoptosis. Furthermore, histopathological results showed significant alteration such as hepatocytes with a pyknotic nucleus, infiltration of inflammatory cells around the central vein, and the presence of many binucleated hepatocytes. Zinc chloride treatment resulted in histological and morphological improvements that were average in the expression of apoptosis proteins modifications induced by cadmium. Our findings revealed that the positive effects of zinc might be linked to the high metallothionein expression and enhanced cell proliferation. Furthermore, at low-dose exposure, cadmium-induced damage to cells could be more closely related to necrosis rather than apoptosis.</p>","PeriodicalId":17421,"journal":{"name":"Journal of Toxicology","volume":"2023 ","pages":"2200539"},"PeriodicalIF":2.9,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9925264/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10727509","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"L-Carnitine Prevents Behavioural Alterations in Ketamine-Induced Schizophrenia in Mice: Possible Involvement of Oxidative Stress and Inflammation Pathways.","authors":"Mehrasa Ebrahimi,&nbsp;Nematollah Ahangar,&nbsp;Ehsan Zamani,&nbsp;Fatemeh Shaki","doi":"10.1155/2023/9093231","DOIUrl":"https://doi.org/10.1155/2023/9093231","url":null,"abstract":"<p><p>Schizophrenia is a chronic mental complaint known as cognitive impairment. There has been evidence that inflammation and oxidative stress play a main role in schizophrenia pathophysiology. This study aimed to investigate the effects of l-carnitine, as a potent antioxidant, on the treatment of behavioural and biochemical disturbances in mice with ketamine-induced schizophrenia. In this study, schizophrenia was induced in mice by ketamine (25 mg/kg/day, <i>i.p</i>). Before induction of schizophrenia, mice were treated with l-carnitine (100, 200, and 400 mg/kg/day, <i>i.p</i>). Then, behavioural impairments were evaluated by open field (OF) assessment and social interaction test (SIT). After brain tissue isolation, reactive oxygen species (ROS), glutathione concentration (GSH), lipid peroxidation (LPO), protein carbonyl oxidation, superoxide dismutase activity (SOD), and glutathione peroxidase activity (GPx) were assessed as oxidative stress markers. Furthermore, inflammatory biomarkers such as tumour necrosis factor alpha (TNF-<i>α</i>) and nitric oxide (NO) were evaluated in brain tissue. Our results showed ketamine increased inflammation and oxidative damage in brain tissue that was similar to behaviour disorders in mice. Interestingly, l-carnitine significantly decreased oxidative stress and inflammatory markers compared with ketamine-treated mice. In addition, l-carnitine prevented and reversed ketamine-induced alterations in the activities of SOD and GPx enzymes in mice's brains. Also, improved performance in OFT (locomotor activity test) and SIT was observed in l-carnitine-treated mice. These data provided evidence that, due to the antioxidant and anti-inflammatory effects of l-carnitine, it has a neuroprotective effect on mice model of schizophrenia.</p>","PeriodicalId":17421,"journal":{"name":"Journal of Toxicology","volume":"2023 ","pages":"9093231"},"PeriodicalIF":2.9,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10289879/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10075887","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Acute and Subacute Toxicity of <i>Rhamnus prinoides</i> Leaves on Histopathology of Liver, Kidney, and Brain Tissues, and Biochemical Profile of Rats.","authors":"Melese Shenkut Abebe","doi":"10.1155/2023/3105615","DOIUrl":"https://doi.org/10.1155/2023/3105615","url":null,"abstract":"<p><p><i>Rhamnus prinoides</i> is used as a traditional medicinal plant to treat pneumonia, sprain, gonorrhea, rheumatism, and ringworm infections as well as for the preparation of local beverages in Ethiopia. It has a widespread antioxidant, antimalarial, antimicrobial, wound healing, and anti-inflammatory activities. These activities are due to the presence of alkaloids, steroids, triterpenes, tannins, flavonoids, flavones, phenols, and glycosides. This study aimed to investigate acute and subacute toxicity of <i>R. prinoides</i> leaves on histopathology of the liver, kidney, and brain tissues, and biochemical profiles of rats. For the acute toxicity study, female rats were treated with <i>R. prinoides</i> at a dose of 5000 mg/kg body weight and followed-up for 14 days. In the subacute toxicity study, four groups of rats were used. The first three groups, respectively, received 250, 500, and 1000 mg/kg body weight of <i>R. prinoides</i> extract and the fourth group was a control group. Signs of toxicity, food intake, and weight was recorded. At necropsy, organ weight measurement and macroscopic and microscopic evaluations of the liver, kidney, and brain were carried out. Different clinical chemistry profiles of rats were also measured. Single-dose oral administration of <i>R. prinoides</i> extract at 5000 mg/kg produced no mortality indicating the LD₅₀ is greater than 5000 mg/kg body weight. A four week administration of <i>R. prinoides</i> extract did not bring deleterious outcomes on the food consumption and weight gain of rats. Moreover, gross examination, histopathological evaluation, and weight measurement conducted on the liver, kidney, and brain did not reveal treatment related changes. The biochemical analysis showed no significant difference between the treatment and control groups. Consumption of <i>R. prinoides</i> leaf for 4 weeks might not have a toxic effect in rats. However, further investigations upon long-term administration should be conducted to have a wider safety margin.</p>","PeriodicalId":17421,"journal":{"name":"Journal of Toxicology","volume":"2023 ","pages":"3105615"},"PeriodicalIF":2.9,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9876683/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10582221","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sublethal Effects of Cadmium on the Osmoregulatory and Acid-Base Parameters of Tilapia (<i>Oreochromis niloticus</i>) at Various Times.","authors":"Agoes Soegianto,&nbsp;Bambang Yulianto,&nbsp;Carolyn Melissa Payus,&nbsp;Moch Affandi,&nbsp;Wildanun Mukholladun,&nbsp;Khudrotul Nisa Indriyasari,&nbsp;Ary Marchellina,&nbsp;Nailul Muthiati Rahmatin","doi":"10.1155/2023/2857650","DOIUrl":"https://doi.org/10.1155/2023/2857650","url":null,"abstract":"<p><strong>Background: </strong>Cadmium (Cd) can contaminate aquatic environments as a result of anthropogenic activity. Cd accumulates quickly in the tissues of fish and has the potential to affect their physiology, including osmoregulation and acid-base balance. Therefore, the purpose of this study was to examine the sublethal effects of Cd on the osmoregulation and acid-base balance of tilapia <i>Oreochromis niloticus</i> at different times.</p><p><strong>Methods: </strong>Fish were exposed to sublethal concentrations of Cd (1 and 2 mg/L) for 4 and 15 days. At the end of the experiment, fish were collected from each treatment to examine the levels of Cd and carbonic anhydrase (CA) in the gills, plasma osmolality, ions, blood pH, pCO₂, pO₂, and hematological parameters.</p><p><strong>Results: </strong>Cd concentrations in gills rose with increasing Cd concentrations in the medium and exposure time. Cd inhibited respiration by generating metabolic acidosis, decreasing gill CA, reducing pO₂, plasma osmolality, Cl^-, and K⁺, particularly at 2 mg/L for 4 days and 1 and 2 mg/L for 15 days. Red blood cell (RBC), hemoglobin (Hb), and hematocrit (Ht) levels decreased as Cd levels in water and exposure duration increased.</p><p><strong>Conclusion: </strong>Cd inhibits respiration, lowers RCB, Hb, and Ht levels and decreases ionic and osmotic regulation. All of these impairments can limit a fish's ability to provide appropriate oxygen to its cells, hence diminishing its physical activity and productivity.</p>","PeriodicalId":17421,"journal":{"name":"Journal of Toxicology","volume":"2023 ","pages":"2857650"},"PeriodicalIF":2.9,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9988379/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9082899","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Acute and Repeated Dose 28-Day Oral Toxicity Study of the Aqueous Extracts from the Leafy Stem and Fruit of <i>Pedalium murex</i> D.Royen EX.L in Wistar Rats.","authors":"Gérard Bessan Dossou-Agoin,&nbsp;Maxime Machioud Sangaré-Oumar,&nbsp;Téniola Isabelle Sacramento,&nbsp;Mariette Sindété,&nbsp;Egnon Jacques Hougbénou-Houngla,&nbsp;Nounagnon Darius Tossavi,&nbsp;Simon Azonbakin,&nbsp;Adam Gbankoto","doi":"10.1155/2023/2962905","DOIUrl":"https://doi.org/10.1155/2023/2962905","url":null,"abstract":"<p><strong>Background: </strong><i>Pedalium murex</i> (<i>P. murex</i>) is used in folk medicine for treatment of male infertility. However, scientific data on its safety are limited.</p><p><strong>Objective: </strong>This study was carried out to assess the acute and repeated dose 28-day oral toxicity of the aqueous extracts from <i>P. murex</i> leafy stem and fruit in Wistar rats.</p><p><strong>Methods: </strong>The acute toxicity test was performed according to the line 423 of the Organization for Economic Cooperation and Development (OECD) guidelines. The rats were randomly divided into three groups (<i>n</i> = 3). The control group received distilled water, while the experimental groups were given at a single dose, 5000 mg/kg of each extract. The repeated dose 28-day oral toxicity was performed according to the line 407 of the OECD guidelines. 35 rats divided into 7 groups of 5 male rats each were daily treated for 28 days with each extract at 200 mg/kg, 400 mg/kg, and 800 mg/kg, respectively. The in-life parameters were recorded during the follow-up. At the end of this study, organ weights, hematology, biochemistry, and histology parameters were analyzed.</p><p><strong>Results: </strong>In the acute oral toxicity test, there was no morbidity or mortality related to the treatments. Both extracts belong therefore to category 5 of the globally harmonized system (GHS) of classification. In the repeated dose 28-day oral toxicity test, both extracts did not alter animal's behavior. However, both extract administration led to proteinuria and renal damages.</p><p><strong>Conclusion: </strong><i>P. murex</i> leafy stem and fruit aqueous extracts exhibited potential nephrotoxicity. Therefore, care should be taken when they are used over an extended period.</p>","PeriodicalId":17421,"journal":{"name":"Journal of Toxicology","volume":"2023 ","pages":"2962905"},"PeriodicalIF":2.9,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10382242/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9910002","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Toxicological Assessments of a Proprietary Blend of Punica granatum Fruit Rind and Theobroma cacao Seed Extracts: Acute, Subchronic, and Genetic Toxicity Studies","authors":"Ravi Kumar Madireddy, K. V. Alluri, Venkateswarlu Somepalli, T. Golakoti, K. Sengupta","doi":"10.1155/2022/3903943","DOIUrl":"https://doi.org/10.1155/2022/3903943","url":null,"abstract":"LN18178 (Tesnor®) is a standardized, proprietary composition of aqueous ethanol extracts of Punica granatum fruit rind and Theobroma cacao seeds. The present study demonstrates a broad-spectrum toxicological evaluation of LN18178 utilizing in vitro and in vivo preclinical models following the Organization for Economic Cooperation and Development (OECD) guidelines for testing chemicals. Wistar rats did not show any clinical signs of toxicity and morbidity in acute oral and dermal toxicity tests with the median lethal dose (LD50) values of at least 5000 mg/kg and 2000 mg/kg body weight, respectively. LN18178 was nonirritating to the skin and eyes of the treated rabbits. In a ninety-day subchronic repeated oral dose toxicity study, the LN18178-treated Wistar rats did not show dose-related signs of toxicity on their body weight, food consumption, organ weights, hematology, and clinical chemistry parameters. The estimated no-observed-adverse-effect level (NOAEL) of LN18178 in male and female rats was 2500 mg/kg body weight. The observations from the bacterial reverse mutation test, in vitro chromosomal aberration assay, micronucleus assay in mouse bone marrow erythrocytes, and in vitro mouse lymphoma TK+/− gene mutation assay suggest that LN18178 is neither mutagenic nor clastogenic. In summary, the present study demonstrates that oral consumption of the herbal blend LN18178 does not show signs of toxicity; also it does not elicit genetic toxicity in the standard preclinical models.","PeriodicalId":17421,"journal":{"name":"Journal of Toxicology","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2022-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41950513","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}