Toxicology Reports最新文献

{"title":"Assessing human exposure to organic contaminants in fish: A modeling approach integrating chemical bioconcentration and food thermal processing.","authors":"Jie Xiong, Yuan Zhang, Zijian Li","doi":"10.1016/j.toxrep.2024.101805","DOIUrl":"https://doi.org/10.1016/j.toxrep.2024.101805","url":null,"abstract":"<p><p>An increasing number of chemicals found in the environment potentially pose a threat to organisms such as fish. Models for risk assessment are vital resources that enable possible measurements of the hazards associated with chemical exposure. Traditional monitoring techniques and experimental procedures, however, are unable to keep up with the compounds that are becoming more and more implicated in environmental problems. Furthermore, a significant amount of data invariably results in inaccuracies. Here, we proposed an integrated approach that combines machine learning and fuzzy logic mathematical methods, assessing the risks associated with chemical exposure from contaminated fish with the least amount of data entry possible. We predicted the concentrations of organic contaminants in the environment, serving as a baseline for quantifying the fuzzy risks during household thermal processing of the fish. With a mean <math> <msup><mrow><mi>R</mi></mrow> <mrow><mn>2</mn></mrow> </msup> </math> value of 0.78, concentration of chemicals in the aquatic environment emerged as the most influential factor in predicting bioconcentration factors. Heptachlor, Endosulfan-sulfate, Endrin, and Endrin aldehyde are four high-risk pesticides throughout the entire processing process compared to others. The findings underscore the importance of considering processing methods and environmental factors in order to ensure food safety.</p>","PeriodicalId":23129,"journal":{"name":"Toxicology Reports","volume":"13 ","pages":"101805"},"PeriodicalIF":0.0,"publicationDate":"2024-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11609693/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142772575","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":"Fisetin attenuates AlCl₃-induced neurodegeneration by modulating oxidative stress and inflammatory cytokine release in adult albino wistar rats.","authors":"Emeka Anyanwu G, Jacinta Nwachukwu I, Rademene Oria S, Kosisochukwu Obasi K, Precious Ekwueme E, Nto Nto J, Chinyere Anyanwu N","doi":"10.1016/j.toxrep.2024.101812","DOIUrl":"https://doi.org/10.1016/j.toxrep.2024.101812","url":null,"abstract":"<p><strong>Aim: </strong>Natural flavonoids have powerful antioxidant and anti-inflammatory activities against neurodegenerative diseases. Fisetin is a powerful flavonoid that targets a variety of neurological disorders. Aluminum (Al) has been linked to several neurological conditions, such as Parkinsons disease, autism, and Alzheimer's disease (AD). This study was designed to assess the modulatory role of fisetin in reversing oxidative stress and neuroinflammation caused by Aluminum chloride (AlCl3) induced neurological conditions in rats.</p><p><strong>Methods: </strong>Adult male Wistar were randomly divided into eight groups of four animals per group. Group 1; the control group received phosphate-buffered saline, group 2 received 100 mg/kg/bodyweight of aluminum chloride, and group 3,4, and 5 received 25, 50, and 75 mg/kg/bodyweight of fisetin respectively for 21 days. Groups 6, 7, and 8 received 25, 50, and 75 mg/kg/bodyweight of fisetin for 14 days followed by 100 mg/kg/bodyweight of aluminum chloride for 7 days respectively. The administration was via the oral route. Following treatment, the rats were euthanized, and biochemical alterations were observed by measuring the serum levels of Glutathione S-Transferase (GST) and Malondialdehyde (MDA) for oxidative stress and Interleukin-6 (IL-6) for neuroinflammation. Furthermore, histopathological evaluations of the thalamus were carried out using routine Hematoxylin and Eosin (H&E) and Cresyl Fast Violet (CFV) techniques while expressions of Glial Fibrillary Acidic Protein (GFAP) for astrocytes, and Ionized Calcium Binding Adapter Molecule 1 (IBA1) for microglia, were examined by immunohistochemical methods.</p><p><strong>Results: </strong>The findings in the AlCl₃ group indicated a rise in lipid peroxidation, decreased antioxidant activity, altered thalamic histomorphology, and increased expression of GFAP and IBA1 markers for astrocytes and microglia, respectively. These effects were mitigated in the Fisetin pretreated groups.</p><p><strong>Conclusion: </strong>These results imply that fisetin can attenuate AlCl₃-induced neurodegeneration possibly by mitigating oxidative stress and neuroinflammation.</p>","PeriodicalId":23129,"journal":{"name":"Toxicology Reports","volume":"13 ","pages":"101812"},"PeriodicalIF":0.0,"publicationDate":"2024-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11609245/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142772593","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":"Investigating the toxicity of malachite green and copper sulfate in brine shrimp: <i>In-vivo</i> and computational study.","authors":"Haja Nazeer Ahamed, Ismail Y, Irfan Navabshan, Mohammed Zaidh S, Shanmugarajan Ts, Ilham Jaleel, Thameemul Ansari Lh","doi":"10.1016/j.toxrep.2024.101811","DOIUrl":"10.1016/j.toxrep.2024.101811","url":null,"abstract":"<p><p>Colour is crucial for enhancing the appetizing value and consumer acceptance of food products. The commonly used food colourants and food preservatives such as Malachite Green (MG) and Copper Sulfate (CS) can cause severe health problems. This study investigates the toxicity of these food-grade colourants through acute exposure using <i>in vivo</i> cytotoxicity using the brine shrimp model including 3D surface analysis (3DSA) and <i>in-silico</i> studies Brine shrimp were treated with various concentrations of MG and CS. The cytotoxic effect was confirmed by brine shrimp lethality assay and 3DSA. Molecular docking and Molecular Dynamic simulation were done using hAChE binding cavity. Results showed that concentrations (2.5-10 µg/ml) of MG and CS significantly decreased locomotor behaviour within 1 h, while higher concentrations (10-100 µg/ml) caused high mortality rates. Morphological studies revealed that there is a significant reduction (p<0.05) in shrimp length treated with MG and CS. The 3DSA indicates that there is an inappropriate surface of the shrimp morphology. Interestingly, MG-treated shrimps had shown significant inhibition of AChE in homogenates, indicating cholinergic nerve-mediated toxicity. Computational studies showed MG confined active binding with human acetylcholinesterase (hAChE), with a binding energy MMGBSA of -51.3 kcal/mol. MD simulation confirmed reversible binding stability inside the hAChE pocket. It can be concluded that acute exposure to brine shrimps with MG and CS exhibited cytotoxicity as evidenced by the increase in mortality of the shrimps. This study further warrants the investigation of MG and CS residues from commonly used fruits and vegetables and their putative toxic effect using <i>in-vivo</i> studies.</p>","PeriodicalId":23129,"journal":{"name":"Toxicology Reports","volume":"13 ","pages":"101811"},"PeriodicalIF":0.0,"publicationDate":"2024-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11617903/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142786711","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":"Novel therapeutic effects of rifaximin in combination with methylprednisolone for LPS-induced ‎oxidative stress and inflammation in mice‎: ‎An <i>in vivo</i> study.","authors":"Marwa Salih Al-Naimi, Ahmed R Abu-Raghif, Hayder Adnan Fawzi","doi":"10.1016/j.toxrep.2024.101808","DOIUrl":"10.1016/j.toxrep.2024.101808","url":null,"abstract":"<p><p>Cytokine-releasing syndrome (CRS) is a special form of ‎‎systemic inflammatory response syndrome provoked by ‎factors ‎like viral infections and certain immunomodulatory drugs.‎ To elucidate the potential ‎role of rifaximin (RIF) and its combination with methylprednisolone (MP) against the development and ‎progression of CRS in ‎mice.‎ This experiment consists of two parts: protective and therapeutic interventions. The protective experiment: in the induction group, mice received an intraperitoneal injection (IP) of 5 mg/kg lipopolysaccharide (LPS) without intervention. The other group received various drugs before the induction by three days, then observed for an additional two days (50 mg/kg MP, 50 mg/kg RIF, and a combination of 25 mg/kg RIF with 25 mg/kg MP. The second part of the study involves the therapeutic potential; all groups received similar doses of drugs to that received in the prevention groups, except LPS induction was given first, and after one hour, the mice received daily doses of the drugs for five days. At the end of the experiment, blood and tissue samples were obtained. Mice treated with RIF and its combination with MP showed improved serum TNF-α, IL-6, IL-8, IL-1β, INF-γ, MDA, and GSH in both prevention and therapeutic groups. Histopathologically, mice treated with rifaximin and its combination with MP ameliorates the tissue damage in both lung and liver tissues following LPS induction. In conclusion, rifaximin showed protective and therapeutic effects in LPS-induced cytokine storms in mice through anti-inflammatory and antioxidant mechanisms, and its combination with methylprednisolone showed additive/ synergistic action.</p>","PeriodicalId":23129,"journal":{"name":"Toxicology Reports","volume":"13 ","pages":"101808"},"PeriodicalIF":0.0,"publicationDate":"2024-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11617758/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142786641","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":"Necroptosis and autophagy in cisplatinum-triggered nephrotoxicity: Novel insights regarding their prognostic and diagnostic potential.","authors":"Mai O Kadry, Rehab M Abdel-Megeed","doi":"10.1016/j.toxrep.2024.101807","DOIUrl":"10.1016/j.toxrep.2024.101807","url":null,"abstract":"<p><p>Necroptosis is an innovative class of programmed autophagy (Atg) and necrosis; considered as a type of homeostatic housekeeping machinery that have observed an escalating concern due to its power in alleviating Cisplatinum-induced nephrotoxicity. This article elucidated in details the prospective role of both autophagy and necroptosis on Cisplatinum-triggered nephrotoxicity and investigating more potent therapy via lactoferrin and Ti-NPS conjugation. Cisplatinum is a commonly used chemotherapeutic drug; one of the limiting adverse actions of cisplatinum is renal toxicity. Upon cisplatinum administration, autophagy is highly stimulated in the kidney to shield against nephrotoxicity. Atg is a lysosomal degradation process which discards detorirated proteins to retain cell homeostasis. This article summarizes necroptosis progress in reconizing cisplatinum nephrotoxicity and debates how this progress can help in discovering more potent therapy via lactoferrin and Ti-NPS conjugation via monitoring autophagy and apoptotic biomarkers X-box-binding protein 1 <i>(XBP),</i> C/EBP homologous protein <i>(CHOP),</i> hypoxanthine phosphoribosyltransferase-1 <i>(HPRT),</i> FKBP prolyl isomerase 1B <i>(FKBP),</i> Cellular myelocytomatosis oncogene <i>(C-myc),</i> tumor suppressor gene <i>(P53)</i> and tumor necrosis factor <i>(TNF-α)</i>. Cisplatinum nephrotoxicity was conducted in rat model via an oral dose of (2 mg/kg BW) for one month furthermore a comparative study was conducted among TiNPs-loaded Cisplatinum and Lactoferrin loaded Cisplatinum. Loaded drug delivery system counteracted Cisplatinum triggered nephrotoxicity via controlling autophagy and apoptotic <i>XBP, CHOP, HPRT, FKBP, C-myc,</i> P53 and TNF-α signaling pathway.</p>","PeriodicalId":23129,"journal":{"name":"Toxicology Reports","volume":"13 ","pages":"101807"},"PeriodicalIF":0.0,"publicationDate":"2024-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11600652/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142740727","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":"Pesticide pollution in India: Environmental and health risks, and policy challenges.","authors":"Urvashi Kashyap, Shivani Garg, Pooja Arora","doi":"10.1016/j.toxrep.2024.101801","DOIUrl":"10.1016/j.toxrep.2024.101801","url":null,"abstract":"<p><p>Intensive agriculture practices in India to meet the food demand of the increasing population have led to the use of agrochemicals such as pesticides in higher quantities to increase productivity resulting in contamination of the environment. Pesticides control pests, weeds, and diseases in plants, animals, and humans. Despite bans on pesticides such as organochlorides (OC), organophosphate (OP), or synthetic pyrethroids ranging from minimal to excessive, are detected in soil, surface water, and groundwater often exceeding WHO and BIS safety limits. The predominantly found pesticides were DDT, HCH, Endosulfan, malathion, chlorpyrifos, atrazine, endrin, cypermethrin, dichlorvos, etc. Different ranges of pesticides were detected in different states (Kashmir, UP, Tamil Nadu, Kerala, Rajasthan, Haryana, Assam, Madhya Pradesh, etc.) of India, which demonstrate that pesticides can persist in the environment and later can show bioaccumulation in the food chain. The article explores the consequences of this pollution such as biomagnification, bioaccumulation, and risks to human health and ecological integrity. This article also covers the adverse effects of pesticides such as carcinogenic, teratogenic, mutagenic, and endocrine-disrupting properties along with the importance of developing new policies or strengthening the current policies and regulations to monitor the use of pesticides.</p>","PeriodicalId":23129,"journal":{"name":"Toxicology Reports","volume":"13 ","pages":"101801"},"PeriodicalIF":0.0,"publicationDate":"2024-11-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11615616/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142781165","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":"An assessment of the prevalence of Aflatoxin M1 level in milk and milk powder based on high performance liquid chromatography and dietary risk assessment.","authors":"Yaser Almasoud, Manar Alwelaie, Zeyad Aldosari, Sarah Alotaibi, Abdullah Alsayari, Ghada Alzyadi, Mohammed Almutairi, Sulaiman Alajel, Abdullah Al Tamim, Hibah Alharbi","doi":"10.1016/j.toxrep.2024.101787","DOIUrl":"https://doi.org/10.1016/j.toxrep.2024.101787","url":null,"abstract":"<p><p>Milk is susceptible to Aflatoxin M1 (AFM1) contamination, mainly through consumption of contaminated animal's feed. The natural occurrence of aflatoxin M1 (AFB1) has been surveyed in samples of milk and milk powder. Samples collected from different regions of Saudi Arabia during the period from 2013 to 2021 were subjected to high-performance liquid chromatography analysis, and (AFB1) was quantified with detection limits of 0.5 µg/kg. The Saudi Food and Drug Authority has taken strong actions to limit AFM1 contamination, increase aflatoxin control, and modify the regulations. A study analyzed 363 randomly collected milk samples (168 milk, 195 milk powder) from Saudi Arabia using LC-MS/MS. Out of the 363 samples, 20 were positive for AFM1, with 343 were within the limits. One out of the 168 milk samples and 19 out of the 195 milk powder samples exceeded the limits, with seven originating from Saudi Arabia. The highest AFM1 concentration (3.97 µg/kg) was found in the Saudi samples. Saudi Arabia's mycotoxin regulations significantly reduced AFM1 contamination in milk, which is not considered a serious health hazard.</p>","PeriodicalId":23129,"journal":{"name":"Toxicology Reports","volume":"13 ","pages":"101787"},"PeriodicalIF":0.0,"publicationDate":"2024-11-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11609700/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142772571","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":"The impact of methamphetamine on liver injury in Iraqi male addicts.","authors":"Nawar S Mohammed, Zahraa Q Ali, Aseel Sameer Mohamed, Sazan Abdulwahab Mirza","doi":"10.1016/j.toxrep.2024.101806","DOIUrl":"https://doi.org/10.1016/j.toxrep.2024.101806","url":null,"abstract":"<p><p>Methamphetamine (METH) is a powerful stimulant that affects neurochemical processes controlling heart rate, appetite, blood pressure, body temperature, and wakefulness, making it highly susceptible to abuse. Liver enzymes such as ALT, AST, ALP, and GGT are crucial for liver function. Albumin, a protein synthesized by healthy liver cells, serves as an indicator of chronic liver disease. Additionally, hepatocytes produce bile acids, which are essential for the secretion of bile salts into the bile canaliculi. Disruption in this secretion results in the accumulation of bile salts in the canaliculi, leading to intrahepatic cholestasis. METH-induced liver toxicity involves disruptions in hepatic metabolism, oxidative stress, and increased body temperature, affecting cellular processes such as cell division and the cell cycle and potentially accelerating liver cell apoptosis. The study explores the link between liver toxicity and hepatocyte damage in Iraqi males suffering from addiction. This is a case-control study, conducted at Ibn-Rushed Psychiatric Hospital in Baghdad from July 2023 to February 2024, involved 196 males, with addiction durations exceeding 24 months with varying degrees of methamphetamine (METH) addiction. The study included 187 healthy male controls with no history of drug addiction. Participants were aged 18-40 years. Diagnosis was confirmed using a drug test screening card administered by a specialist. The study included liver function tests (ALT, AST, ALP, and GGT), total bilirubin, and albumin concentration assessments. Significant differences were observed between the addicts and controls, particularly a marked decrease in serum albumin concentration in the addicted males. The ROC curve classification model at various thresholds demonstrated that liver enzymes, especially ALT, ALP, and GGT, exhibited increased sensitivity to METH addiction. A histopathological examination was conducted on a deceased 38-year-old male who had a six-year history of chronic amphetamine addiction to confirm liver injury and the resulting elevation of liver enzymes. The findings of this study indicate that METH greatly affects liver function, suggested to the importance of following a preventative measures and effective treatment approaches for monitoring METH addiction progress.</p>","PeriodicalId":23129,"journal":{"name":"Toxicology Reports","volume":"13 ","pages":"101806"},"PeriodicalIF":0.0,"publicationDate":"2024-11-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11609243/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142772610","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":"Comprehensive risk-benefit assessment of chemicals: A case study on glyphosate.","authors":"Alberto Boretti","doi":"10.1016/j.toxrep.2024.101803","DOIUrl":"10.1016/j.toxrep.2024.101803","url":null,"abstract":"<p><p>The integrity of environmental toxicology is undermined by selective risk assessments that focus intently on certain chemicals while overlooking others. Glyphosate, one of the most widely used herbicides, serves as a case study of how regulatory decisions can be shaped by incomplete or biased evidence. This paper argues for a holistic approach to toxicology, calling for balanced assessments that consider both health risks and societal benefits. It critically examines current regulatory practices concerning glyphosate, investigating its association with non-Hodgkin's lymphoma and its positive effects on agricultural productivity and food security. While definitive evidence linking glyphosate to cancer remains inconclusive, its role in enhancing crop yields, by as much as 20 % in some regions, has had measurable benefits for food security and public health. The paper advocates for regulatory frameworks that transparently weigh these societal benefits against potential health risks, particularly in settings of occupational exposure, where the need for balanced assessment is especially pressing. Through a narrative review of major studies, this paper underscores the need for transparency, accountability, and evidence-based approaches in environmental regulation. Such practices are essential for crafting policies that not only mitigate risk but also promote global food security and well-being. By integrating both risks and benefits into the regulatory process, the study proposes an inclusive and data-driven approach to chemical policy that aligns with the broader goals of sustainability and public health.</p>","PeriodicalId":23129,"journal":{"name":"Toxicology Reports","volume":"13 ","pages":"101803"},"PeriodicalIF":0.0,"publicationDate":"2024-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11600065/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142740725","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":"Nephroprotective effects of the soluble guanylyl cyclase stimulator, riociguat in doxorubicin-induced acute kidney injury in rats.","authors":"Raya Al-Maskari, Aly M Abdelrahman, Haytham Ali, Priyadarsini Manoj, Yousuf Al Suleimani","doi":"10.1016/j.toxrep.2024.101800","DOIUrl":"10.1016/j.toxrep.2024.101800","url":null,"abstract":"<p><p>This study aimed to investigate the potential protective effects of riociguat, a soluble guanylyl cyclase (sGC) stimulator, on kidney function and structure in rats with acute kidney injury (AKI) induced by the chemotherapeutic drug doxorubicin (DX). Rats were subjected to a single intraperitoneal injection of DX (13.5 mg/kg) on the 5th day, either alone or in combination with low-dose riociguat (3 mg/kg/day), or high-dose riociguat (10 mg/kg/day) for 8 consecutive days. Various markers related to kidney function, oxidative stress, and inflammation were measured in plasma and urine. Kidney tissues were examined histopathologically. DX-induced nephrotoxicity was characterized by increased plasma urea, creatinine, uric acid and neutrophil gelatinase-associated lipocalin (NGAL). DX also decreased creatinine clearance and albumin levels and increased urinary N-acetyl-β-D-glucosaminidase (NAG) activity. Furthermore, DX increased the inflammatory markers interleukin 1 beta (IL-1 β), interleukin 6 (IL-6) and tumor necrosis factor alpha (TNF-α). DX further induced oxidative stress injury evidenced by decreased glutathione reductase (GR) activity, total antioxidant capacity (TAC), superoxide dismutase (SOD) and catalase levels and increased malondialdehyde (MDA) levels. Concomitant treatment with riociguat ameliorated these DX-induced changes with parallel histopathological improvements but the effects were more favorable with high-dose riociguat. The observed renoprotective effects of riociguat can be partly attributed to the anti-inflammatory and anti-oxidant properties of this drug.</p>","PeriodicalId":23129,"journal":{"name":"Toxicology Reports","volume":"13 ","pages":"101800"},"PeriodicalIF":0.0,"publicationDate":"2024-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11600010/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142740728","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}