Drug and Chemical Toxicology最新文献

{"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}

{"title":"Dermatoprotective effect of <i>Moringa oleifera</i> leaf extract on sodium valproate-induced skin damage in rats.","authors":"Gülsüm Elik, Sehkar Oktay, Ismet Burcu Turkyilmaz, Burcin Alev-Tuzuner, Umar Faruk Magaji, Ozlem Sacan, Refiye Yanardag, Aysen Yarat","doi":"10.1080/01480545.2024.2369586","DOIUrl":"10.1080/01480545.2024.2369586","url":null,"abstract":"<p><p>Valproic acid is an antiepileptic drug associated with skin-related issues like excessive hair growth, hair loss, and skin rashes. In contrast, <i>Moringa oleifera</i>, rich in nutrients and antioxidants, is gaining popularity worldwide for its medicinal properties. The protective properties of <i>M. oleifera</i> extract against skin-related side effects caused by valproic acid were investigated. Female rats were divided into control groups and experimental groups such as moringa, sodium valproate, and sodium valproate + moringa groups. A 70% ethanolic extract of moringa (0.3 g/kg/day) was given to moringa groups, and a single dose of sodium valproate (0.5 g/kg/day) was given to valproate groups for 15 days. In the skin samples, antioxidant parameters (such as glutathione, glutathione-S-transferase, superoxide dismutase, catalase, and total antioxidant capacity), as well as oxidant parameters representing oxidative stress (i.e. lipid peroxidation, sialic acid, nitric oxide, reactive oxygen species, and total oxidant capacity), were examined. Additionally, boron, hydroxyproline, sodium-potassium ATPase, and tissue factor values were determined. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis was also carried out for protein analysis in the skin samples. The results showed that moringa could increase glutathione, total antioxidant capacity, sodium-potassium ATPase, and boron levels, while decreasing lipid peroxidation, sialic acid, nitric oxide, total oxidant capacity, reactive oxygen species, hydroxyproline, and tissue factor levels. These findings imply that moringa possesses the potential to mitigate dermatological side effects.</p>","PeriodicalId":11333,"journal":{"name":"Drug and Chemical Toxicology","volume":" ","pages":"1257-1266"},"PeriodicalIF":2.1,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141562947","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":"Human red blood cell acetylcholinesterase activity: a revisit after fifteen years.","authors":"Pucheng Ke, Ralph A Stidham, Marisol S Castaneto, Adrienne M Forbes, Robert L Fathke, Robert B Crochet, Jeremy W Lewis, Matthew D Wegner, Stephanie L Mont","doi":"10.1080/01480545.2024.2329752","DOIUrl":"10.1080/01480545.2024.2329752","url":null,"abstract":"<p><p>Human red blood cell acetylcholinesterase (RBC-AChE) activity is valuable for detecting potential exposure to cholinesterase inhibiting substances (CIS). A reliable population-based RBC-AChE activity reference range is critical for early and massive clinical and occupational toxicology screening. Previous published studies were often limited to small numbers of subjects, various testing methods, and crude statistical data analyses. We tested 4818 adult subjects with a well-established 17-minute modified Michel method over a 2-year period. We conducted a retrospective data analysis and systematically investigated on the influences to testing values from gender, age, age group, and their combinations and interactions. No significant difference was observed in the testing values between males (mean, medium, interquartile range = 0.76, 0.76, 0.71-0.80 ΔpH/h, respectively) and females (mean, medium, interquartile range = 0.76, 0.76, 0.71-0.81 ΔpH/hour, respectively), when gender was the only factor considered (<i>p</i> = 0.7238). However, with age progression, male testing values exhibited a consistent upward trend, while females did not show any clear patterns. Linear regression analysis of the data revealed that gender, age, and age group more or less affected testing values either as independent variables or with their combinations and interactions. However, more potential factors need to be included to achieve better testing value predictions. We recommend the toxicological testing community to adopt a new set of age group specific RBC-AChE activity reference ranges for males (0.68-0.80, 0.69-0.81, 0.70-0.83, 0.71-0.84, and 0.73-0.87 ΔpH/h for 18-29, 30-39, 40-49, 50-59, and ≥60 years old, respectively) while keeping the current reference range (0.63-0.89 ΔpH/hour) for females.</p>","PeriodicalId":11333,"journal":{"name":"Drug and Chemical Toxicology","volume":" ","pages":"1050-1057"},"PeriodicalIF":2.1,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140174082","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":"Water-soluble phenolics from <i>Phoenix dactylifera</i> fruits as potential reno-protective agent against cisplatin-induced toxicity: pre- and post-treatment strategies.","authors":"Omowumi Oyeronke Adewale, Roseline Fadera Oyelola, Oluwatosin Adefunke Adetuyi, Oluwaseun Abraham Adebisi, Damilare Adedayo Adekomi, Johnson Olaleye Oladele","doi":"10.1080/01480545.2024.2329762","DOIUrl":"10.1080/01480545.2024.2329762","url":null,"abstract":"<p><p>Nephrotoxicity is the major side effect of cisplatin, an effective platinum-based chemotherapeutic drug that is applicable in the treatment of several solid-tissue cancers. Studies have indicated that certain water-soluble phenolics offer renal protection. Thus, this study investigates the role of pre and post-treatment of rats with water-soluble phenolics from <i>Phoenix dactylifera</i> (PdP) against nephrotoxicity induced by cisplatin. Rats were either orally pretreated or post-treated with 200 mg/kg body weight of PdP before or after exposure to a single therapeutic dose of cisplatin (5 mg/kg body weight) for 7 successive days intraperitoneally. The protective effects of PdP against Cisplatin-induced nephrotoxicity was based on the evaluation of various biochemical and redox biomarkers, together with histopathological examination of kidney tissues. The composition, structural features, and antioxidative influence of PdP were determined based on chromatographic, spectroscopic, and in vitro antioxidative models. Cisplatin single exposure led to a substantial increase in the tested renal function biomarkers (uric acid, creatinine, and urea levels), associated with an increase in malondialdehyde indicating lipid peroxidation and a significant decline (<i>p</i> < 0.05) in reduced glutathione (GSH) levels in the renal tissue when compared with the control group. A marked decline exists in the kidney antioxidant enzymes (catalase, SOD, and GPx). Nevertheless, treatment with PdP significantly suppressed the heightened renal function markers, lipid peroxidation, and oxidative stress. Spectroscopic analysis revealed significant medicinal phenolics, and in vitro tests demonstrated antioxidative properties. Taken together, results from this study indicate that pre- and/or post-treatment strategies of PdP could serve therapeutic purposes in cisplatin-induced renal damage.</p>","PeriodicalId":11333,"journal":{"name":"Drug and Chemical Toxicology","volume":" ","pages":"1058-1071"},"PeriodicalIF":2.1,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140287115","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}