Pub Date : 2026-01-16DOI: 10.1016/j.toxrep.2026.102207
Natasha Sura Anak Lubau , Vinod Balasubramaniam , Christina Gertrude Yap , Alina Arulsamy , Vetriselvan Subramaniyan
Karanjin (KRN) is a benzofuran flavonoid derived from Pongamia pinnata seeds, known for its antihyperglycemic and anti-inflammatory properties. Despite its traditional use, comprehensive toxicological data are limited. This study evaluated the acute and subacute oral toxicity of KRN in Sprague Dawley rats. In the acute study, single doses of 5, 500, or 2000 mg/kg were administered, and animals were observed for 14 days. In the subacute study, daily doses of 5, 50, or 250 mg/kg were given for 28 days. Clinical signs, body weight, food and water intake were monitored throughout. At termination, organs (liver, kidney, heart, etc.) were weighed, blood was analysed for biochemical parameters (ALT, AST, ALP, total protein, albumin, lipids), and tissues were examined histopathologically. No mortality or treatment-related clinical signs occurred at any dose. Body weight, food/water intake, and organ weights did not differ significantly between treated and control groups. Serum biochemical values remained within normal limits, showing only minor, non-dose-dependent variations. Histopathology revealed normal architecture of major organs without evidence of necrosis, inflammation, or degeneration. These findings demonstrate a wide margin of safety for oral KRN and support its potential for further pharmacological development.
{"title":"Acute and subacute oral toxicity assessment of Karanjin in Sprague Dawley rats","authors":"Natasha Sura Anak Lubau , Vinod Balasubramaniam , Christina Gertrude Yap , Alina Arulsamy , Vetriselvan Subramaniyan","doi":"10.1016/j.toxrep.2026.102207","DOIUrl":"10.1016/j.toxrep.2026.102207","url":null,"abstract":"<div><div>Karanjin (KRN) is a benzofuran flavonoid derived from <em>Pongamia pinnata</em> seeds, known for its antihyperglycemic and anti-inflammatory properties. Despite its traditional use, comprehensive toxicological data are limited. This study evaluated the acute and subacute oral toxicity of KRN in Sprague Dawley rats. In the acute study, single doses of 5, 500, or 2000 mg/kg were administered, and animals were observed for 14 days. In the subacute study, daily doses of 5, 50, or 250 mg/kg were given for 28 days. Clinical signs, body weight, food and water intake were monitored throughout. At termination, organs (liver, kidney, heart, etc.) were weighed, blood was analysed for biochemical parameters (ALT, AST, ALP, total protein, albumin, lipids), and tissues were examined histopathologically. No mortality or treatment-related clinical signs occurred at any dose. Body weight, food/water intake, and organ weights did not differ significantly between treated and control groups. Serum biochemical values remained within normal limits, showing only minor, non-dose-dependent variations. Histopathology revealed normal architecture of major organs without evidence of necrosis, inflammation, or degeneration. These findings demonstrate a wide margin of safety for oral KRN and support its potential for further pharmacological development.</div></div>","PeriodicalId":23129,"journal":{"name":"Toxicology Reports","volume":"16 ","pages":"Article 102207"},"PeriodicalIF":0.0,"publicationDate":"2026-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146022731","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}
The increasing global use of Mitragyna speciosa (Kratom) necessitates a thorough safety assessment, particularly regarding the genotoxic potential of its key alkaloids. This study employed an integrated in silico and in vitro approach to evaluate the genotoxicity of a well-characterized, semi-synthetically enhanced Kratom preparation (SKP) enriched in 7-hydroxymitragynine (7-OHMG; 56.31 % of total composition). Computational predictions using the OECD QSAR Toolbox and VEGA-QSAR platform indicated a lack of genotoxic activity for the major Kratom alkaloids (mitragynine, paynantheine, speciogynine, 7-hydroxymitragynine, and speciociliatine) across various in vitro and in vivo endpoints. However, several DNA-binding structural alerts were identified, particularly under metabolic activation, and prediction reliability ranged from low to moderate. To empirically verify these findings, an in vitro cytokinesis-block micronucleus (CBMN) assay was conducted in human TK6 cells following OECD Test Guideline 487. The extract induced concentration-dependent cytotoxicity. A statistically significant increase in micronucleus frequency was observed only at the highest concentration tested (125 µg/mL) under short-term (4 h) exposure conditions, both with and without S9 metabolic activation. Excessive cytotoxicity prevented analysis at high concentrations during long-term (24 h) exposure. Importantly, a complementary bacterial reverse mutation assay (Ames test) conducted on the identical extract showed no mutagenic activity up to 5000 µg/plate across five strains. In conclusion, while a weak positive chromosomal effect was noted at a highly cytotoxic concentration, the overall weight of evidence—including negative in silico predictions, negative Ames results, and limited in vitro micronucleus response—suggests that this 7-OHMG-enriched Kratom preparation does not present a significant genotoxic hazard under the conditions tested. This study underscores the value of a combined computational and experimental workflow for the robust genotoxicity assessment of complex natural products.
{"title":"Genotoxicity risk assessment of a 7-hydroxymitragynine-enriched Kratom preparation: An integrated in silico and in vitro approach","authors":"Nathaphat Harnkit , Tiyanee Sahad , Ittiya Noonate , Phatiphan Primpai , Sarayut Radapong , Weerachai Pipatrattanaseree , Pornchai Sincharoenpokai , Pramote Chamnanpuen","doi":"10.1016/j.toxrep.2026.102206","DOIUrl":"10.1016/j.toxrep.2026.102206","url":null,"abstract":"<div><div>The increasing global use of <em>Mitragyna speciosa</em> (Kratom) necessitates a thorough safety assessment, particularly regarding the genotoxic potential of its key alkaloids. This study employed an integrated in silico and in vitro approach to evaluate the genotoxicity of a well-characterized, semi-synthetically enhanced Kratom preparation (SKP) enriched in 7-hydroxymitragynine (7-OHMG; 56.31 % of total composition). Computational predictions using the OECD QSAR Toolbox and VEGA-QSAR platform indicated a lack of genotoxic activity for the major Kratom alkaloids (mitragynine, paynantheine, speciogynine, 7-hydroxymitragynine, and speciociliatine) across various in vitro and in vivo endpoints. However, several DNA-binding structural alerts were identified, particularly under metabolic activation, and prediction reliability ranged from low to moderate. To empirically verify these findings, an in vitro cytokinesis-block micronucleus (CBMN) assay was conducted in human TK6 cells following OECD Test Guideline 487. The extract induced concentration-dependent cytotoxicity. A statistically significant increase in micronucleus frequency was observed only at the highest concentration tested (125 µg/mL) under short-term (4 h) exposure conditions, both with and without S9 metabolic activation. Excessive cytotoxicity prevented analysis at high concentrations during long-term (24 h) exposure. Importantly, a complementary bacterial reverse mutation assay (Ames test) conducted on the identical extract showed no mutagenic activity up to 5000 µg/plate across five strains. In conclusion, while a weak positive chromosomal effect was noted at a highly cytotoxic concentration, the overall weight of evidence—including negative in silico predictions, negative Ames results, and limited in vitro micronucleus response—suggests that this 7-OHMG-enriched Kratom preparation does not present a significant genotoxic hazard under the conditions tested. This study underscores the value of a combined computational and experimental workflow for the robust genotoxicity assessment of complex natural products.</div></div>","PeriodicalId":23129,"journal":{"name":"Toxicology Reports","volume":"16 ","pages":"Article 102206"},"PeriodicalIF":0.0,"publicationDate":"2026-01-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145977348","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}
Pub Date : 2026-01-14DOI: 10.1016/j.toxrep.2026.102205
Protais Mukunzi , Ben Shalom Byishimo , Ekom Monday Etukudo , Hyppolyte Iradukunda , Darius Benimana , Ibe Michael Usman , Augustin Oviosun , Comfort Ojochenemi Usman , David Ikwuka , Wusa Makena , Victor Bassey Archibong
In recent time, the use of medicinal plants in the management of human disease conditions has gained immense attention. The aim of the present review was to explore the phytochemical composition and anti-Alzheimer potential of medicinal plants from Central and West Africa. A structured systematic approach was used to conduct the present systematic review of articles. Scopus, PubMed, and Web of Science were searched using the following search terms combined by Boolean operators: (“Alzheimer’s disease” OR “Neurodegenerative disease” OR "Nervous system diseases") AND (“Extract” OR "herbs" OR “Plant”) AND (“West Africa” OR “Central Africa” OR “Africa”) on the 6th of July 2024 without any filters. Following the conclusion of the title, abstract, and full text screening, only 13 articles were included. Most of the included studies (10/13, 77 %) were conducted between 2014 and 2024. Geographically, 9 (69 %) studies were conducted in Nigeria. Plants identified in the present study include: Solanum macrocarpon, Solanum nigru, Pteleopsis suberosa, Macrosphyra longistyl, Beta vulgaris, Persea americana, Syzygium aromaticum, Citrullus lanatus, Cucumeropsis mannii, Lagenaria siceraria, Achyranthes aspera Linn., Tithonia diversifolia. These plants were found to contain Luteolin, Catechin, Decanoic acid methyl ester, 11,14-Eicosadienoic acid methyl ester, Caffeic acid, Syringic acid, Azelaic acid. The plant-derived phytochemicals were reported to modulate critical Alzheimer’s disease (AD) pathways, notably oxidative stress, acetylcholinesterase (AChE) inhibition, and neuroinflammation. In conclusion, Central and West African medicinal plants represent a rich reservoir of multifunctional neuroprotective metabolites capable of targeting diverse AD pathways.
近年来，药用植物在人类疾病状况管理中的应用获得了极大的关注。本综述旨在探讨中非和西非药用植物的植物化学成分及其抗阿尔茨海默病的潜力。采用结构化的系统方法对文章进行系统评价。Scopus， PubMed和Web of Science在2024年7月6日使用布尔运算符组合的以下搜索词进行搜索：（“阿尔茨海默病”或“神经退行性疾病”或“神经系统疾病”）和（“提取物”或“草药”或“植物”）和（“西非”或“中非”或“非洲”），没有任何过滤器。在结束题目、摘要和全文筛选之后，只有13篇文章被纳入。大多数纳入的研究（10/13,77 %）是在2014 - 2024年间进行的。从地理上看，在尼日利亚进行了9项（69 %）研究。本研究鉴定的植物包括：大龙葵、黑龙葵、羽绒拟南芥、长柱大龙葵、甜菜、美洲波斯、香薷、瓜柳、甘露黄瓜、木犀草、牛膝牛膝。，金银花。这些植物含有木犀草素、儿茶素、癸酸甲酯、11,14-二十二烯酸甲酯、咖啡酸、丁香酸、壬二酸。据报道，植物源性植物化学物质可调节阿尔茨海默病（AD）的关键途径，特别是氧化应激、乙酰胆碱酯酶（AChE）抑制和神经炎症。综上所述，中非和西非药用植物具有丰富的多功能神经保护代谢物，能够靶向不同的AD通路。
{"title":"Phytochemical composition and anti-Alzheimer potential of medicinal plants from Central and West Africa: Systematic review","authors":"Protais Mukunzi , Ben Shalom Byishimo , Ekom Monday Etukudo , Hyppolyte Iradukunda , Darius Benimana , Ibe Michael Usman , Augustin Oviosun , Comfort Ojochenemi Usman , David Ikwuka , Wusa Makena , Victor Bassey Archibong","doi":"10.1016/j.toxrep.2026.102205","DOIUrl":"10.1016/j.toxrep.2026.102205","url":null,"abstract":"<div><div>In recent time, the use of medicinal plants in the management of human disease conditions has gained immense attention. The aim of the present review was to explore the phytochemical composition and anti-Alzheimer potential of medicinal plants from Central and West Africa. A structured systematic approach was used to conduct the present systematic review of articles. Scopus, PubMed, and Web of Science were searched using the following search terms combined by Boolean operators: (“Alzheimer’s disease” OR “Neurodegenerative disease” OR \"Nervous system diseases\") AND (“Extract” OR \"herbs\" OR “Plant”) AND (“West Africa” OR “Central Africa” OR “Africa”) on the 6th of July 2024 without any filters. Following the conclusion of the title, abstract, and full text screening, only 13 articles were included. Most of the included studies (10/13, 77 %) were conducted between 2014 and 2024. Geographically, 9 (69 %) studies were conducted in Nigeria. Plants identified in the present study include: <em>Solanum macrocarpon</em>, <em>Solanum nigru, Pteleopsis suberosa, Macrosphyra longistyl, Beta vulgaris, Persea americana, Syzygium aromaticum, Citrullus lanatus, Cucumeropsis mannii, Lagenaria siceraria, Achyranthes aspera Linn., Tithonia diversifolia.</em> These plants were found to contain Luteolin, Catechin, Decanoic acid methyl ester, 11,14-Eicosadienoic acid methyl ester, Caffeic acid, Syringic acid, Azelaic acid. The plant-derived phytochemicals were reported to modulate critical Alzheimer’s disease (AD) pathways, notably oxidative stress, acetylcholinesterase (AChE) inhibition, and neuroinflammation. In conclusion, Central and West African medicinal plants represent a rich reservoir of multifunctional neuroprotective metabolites capable of targeting diverse AD pathways.</div></div>","PeriodicalId":23129,"journal":{"name":"Toxicology Reports","volume":"16 ","pages":"Article 102205"},"PeriodicalIF":0.0,"publicationDate":"2026-01-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145977241","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}
This study evaluated the effects of berberine nanoemulsion (BNE) against nephrotoxicity induced by bisphenol A (BPA), a plastic chemical, in rats during the pre-puberty stage. Thirty-six male Wistar rats (23-day-old) were randomly allocated to six groups (n = 6): Group 1 (Control). Group 2 (BPA): BPA (200 mg/kg) and saline. Groups 3 (BNE 5) and 4 (BNE 10): BNE (5 and 10 mg/kg,). Groups 5 (BPA + BNE 5) and 6 (BPA + BNE 10): BPA with BNE (5 and 10 mg/kg). After 30 days, kidney samples were obtained for histopathological and biochemical tests. BPA increased serum urea, uric acid, creatinine (Cr), blood urea nitrogen (BUN), and kidney levels of malondialdehyde (MDA), nitric oxide (NO), interleukin-6 (IL-6), interleukin-1β (IL-1β), and tumor necrosis factor-α (TNF-α) versus controls. BPA decreased estimated glomerular filtration rate (eGFR), reduced glutathione (GSH), and superoxide dismutase (SOD) activity. BNE (10 mg/kg) reversed these changes to near-control levels. Histopathology showed lumen obliteration of renal tubules, dilated vessels, glomerular atrophy, and large capsular space in the BPA group. Less inflammation and improved glomerular architecture were seen in the BPA + BNE10 group. In conclusion, BNE (10 mg/kg) significantly alleviated BPA-induced oxidative stress, inflammation and histopathological changes in the kidney of rats during the pre-puberty stage due to its antioxidant and anti-inflammatory effects. This finding confirms the safety and efficacy of BNE in nephrotoxic model during pre-puberty stage. It can be suggested to investigate this agent in clinical study as a possible therapeutic approach.
{"title":"Berberine nanoemulsion against nephrotoxicity induced by bisphenol a in rats during pre-puberty stage","authors":"Shahnaz Rajabi , Atena Mansouri , Tahora Fakhrtaha , Parisa Sadighara , Fariborz Samini , Saeed Samarghandian , Tahereh Farkhondeh","doi":"10.1016/j.toxrep.2026.102203","DOIUrl":"10.1016/j.toxrep.2026.102203","url":null,"abstract":"<div><div>This study evaluated the effects of berberine nanoemulsion (BNE) against nephrotoxicity induced by bisphenol A (BPA), a plastic chemical, in rats during the pre-puberty stage. Thirty-six male Wistar rats (23-day-old) were randomly allocated to six groups (n = 6): Group 1 (Control). Group 2 (BPA): BPA (200 mg/kg) and saline. Groups 3 (BNE 5) and 4 (BNE 10): BNE (5 and 10 mg/kg,). Groups 5 (BPA + BNE 5) and 6 (BPA + BNE 10): BPA with BNE (5 and 10 mg/kg). After 30 days, kidney samples were obtained for histopathological and biochemical tests. BPA increased serum urea, uric acid, creatinine (Cr), blood urea nitrogen (BUN), and kidney levels of malondialdehyde (MDA), nitric oxide (NO), interleukin-6 (IL-6), interleukin-1β (IL-1β), and tumor necrosis factor-α (TNF-α) versus controls. BPA decreased estimated glomerular filtration rate (eGFR), reduced glutathione (GSH), and superoxide dismutase (SOD) activity. BNE (10 mg/kg) reversed these changes to near-control levels. Histopathology showed lumen obliteration of renal tubules, dilated vessels, glomerular atrophy, and large capsular space in the BPA group. Less inflammation and improved glomerular architecture were seen in the BPA + BNE10 group. In conclusion, BNE (10 mg/kg) significantly alleviated BPA-induced oxidative stress, inflammation and histopathological changes in the kidney of rats during the pre-puberty stage due to its antioxidant and anti-inflammatory effects. This finding confirms the safety and efficacy of BNE in nephrotoxic model during pre-puberty stage. It can be suggested to investigate this agent in clinical study as a possible therapeutic approach.</div></div>","PeriodicalId":23129,"journal":{"name":"Toxicology Reports","volume":"16 ","pages":"Article 102203"},"PeriodicalIF":0.0,"publicationDate":"2026-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146173139","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}
Pub Date : 2026-01-08DOI: 10.1016/j.toxrep.2026.102204
Elaf Mahmood Shihab , Saba Naseer Abbas , Saja Majeed Shareef , Rana Jawad Hasan , Khulood Majid Alsaraf , Hayder Adnan Fawzi
Purpose
Azilsartan, a unique angiotensin II receptor blocker (ARB) with an oxo-oxadiazole ring, exhibits antioxidant and anti-inflammatory properties, but its role in ferroptosis-mediated AKI remains unexplored. This study investigates whether azilsartan protects against FA-induced AKI in male mice by attenuating ferroptosis, modulating iron metabolism, and suppressing inflammatory signaling.
Methods
42 male C57BL/6 J mice were randomized into six groups: control, FA-induced AKI, three azilsartan doses (1, 3, 5 mg/kg), and ferrostatin-1 (Fer-1) as a positive control. Azilsartan or Fer-1 was administered for 7 days before FA injection (250 mg/kg, i.p.) and continued for 3 days post-induction. Renal function (serum urea, creatinine), ferroptosis markers (GPX4, MDA, Nrf2, SLC7A11, HO-1), iron-handling proteins (ferritin, TfR1), inflammatory mediators (TNF-α, NF-κB p65), and histopathology were assessed.
Results
FA-AKI caused marked renal dysfunction, elevated KIM-1, lipid peroxidation, depletion of GPX4, downregulation of Nrf2/HO-1/SLC7A11 and TfR1, reduction of transferrin levels, and inflammatory activation. Azilsartan improved renal function and histology in a dose-dependent manner, restored GPX4, reduced MDA, upregulated Nrf2/HO-1/SLC7A11 and TfR1, increased ferritin levels, and suppressed TNF-α/NF-κB. High-dose azilsartan achieved effects comparable to those of Fer-1.
Conclusion
Azilsartan confers potent protection against FA-induced AKI by activating the Nrf2/HO-1/SLC7A11/GPX4 axis, reducing lipid peroxidation, normalizing iron metabolism, and attenuating inflammation. These findings support azilsartan’s potential as a repurposed therapy for ferroptosis-driven renal injury.
{"title":"Azilsartan as a novel anti-ferriptotic agent via the upregulation of the Nrf2/HO-1/SLC7A11/GPX4 axis and downregulation of inflammatory pathways in folic acid-induced acute kidney injury in male mice","authors":"Elaf Mahmood Shihab , Saba Naseer Abbas , Saja Majeed Shareef , Rana Jawad Hasan , Khulood Majid Alsaraf , Hayder Adnan Fawzi","doi":"10.1016/j.toxrep.2026.102204","DOIUrl":"10.1016/j.toxrep.2026.102204","url":null,"abstract":"<div><h3>Purpose</h3><div>Azilsartan, a unique angiotensin II receptor blocker (ARB) with an oxo-oxadiazole ring, exhibits antioxidant and anti-inflammatory properties, but its role in ferroptosis-mediated AKI remains unexplored. This study investigates whether azilsartan protects against FA-induced AKI in male mice by attenuating ferroptosis, modulating iron metabolism, and suppressing inflammatory signaling.</div></div><div><h3>Methods</h3><div>42 male C57BL/6 J mice were randomized into six groups: control, FA-induced AKI, three azilsartan doses (1, 3, 5 mg/kg), and ferrostatin-1 (Fer-1) as a positive control. Azilsartan or Fer-1 was administered for 7 days before FA injection (250 mg/kg, i.p.) and continued for 3 days post-induction. Renal function (serum urea, creatinine), ferroptosis markers (GPX4, MDA, Nrf2, SLC7A11, HO-1), iron-handling proteins (ferritin, TfR1), inflammatory mediators (TNF-α, NF-κB p65), and histopathology were assessed.</div></div><div><h3>Results</h3><div>FA-AKI caused marked renal dysfunction, elevated KIM-1, lipid peroxidation, depletion of GPX4, downregulation of Nrf2/HO-1/SLC7A11 and TfR1, reduction of transferrin levels, and inflammatory activation. Azilsartan improved renal function and histology in a dose-dependent manner, restored GPX4, reduced MDA, upregulated Nrf2/HO-1/SLC7A11 and TfR1, increased ferritin levels, and suppressed TNF-α/NF-κB. High-dose azilsartan achieved effects comparable to those of Fer-1.</div></div><div><h3>Conclusion</h3><div>Azilsartan confers potent protection against FA-induced AKI by activating the Nrf2/HO-1/SLC7A11/GPX4 axis, reducing lipid peroxidation, normalizing iron metabolism, and attenuating inflammation. These findings support azilsartan’s potential as a repurposed therapy for ferroptosis-driven renal injury.</div></div>","PeriodicalId":23129,"journal":{"name":"Toxicology Reports","volume":"16 ","pages":"Article 102204"},"PeriodicalIF":0.0,"publicationDate":"2026-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145977345","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}
Hemp-derived cannabinoids (CBDs) such as Δ8- and Δ10-tetrahydrocannabinol (THC) in cannabis e-cigarettes have been growing in popularity among youth, causing great concern for their health effects. Previous novel lung injury outbreaks, such as E-cigarette or Vaping Use-Associated Lung Injury (EVALI), were associated with the rising use of e-cigarettes and vaping products. Toxicological studies have revealed that chronic exposure to cannabis vapor can cause adverse brain and pulmonary effects. Hemp products are classified as cannabis and set a limit of no more than 0.3 % Δ9-THC, while products containing more than 0.3 % are defined as ‘marijuana.’ This has led to the proliferation of hemp-derived intoxicating cannabinoids, such as Δ8- and Δ10-THC, in addition to cannabidiol (CBD), cannabinol (CBN), cannabigerol (CBG), and Δ9-THC appearing in combination products. CBD frequently serves as a significant component of hemp-derived formulations, making it a central consideration for toxicological and regulatory evaluation as well. This phenomenon poses significant health risks to youth because these newer THC isomers and products are currently unregulated and not well-researched, yet they are still widely available. Therefore, we have examined the pharmacology, toxicity, potential therapeutic uses and possible health risks of several THC and hemp-derived cannabinoids. This review draws insightful highlights to the public health consequences of secondary exposures to CBD and THC, and their molecular mechanisms of action. It underscores the urgency for a regulatory oversight over unregulated cannabinoid markets to prevent toxicity of vaping-related health crises and other rapidly emerging cannabis health disorders, like the cannabinoid hyperemesis syndrome (CHS).
{"title":"Toxicity and health effects of delta-8, delta-9, and delta-10-tetrahydrocannabinol and unregulated cannabinoids in vaping products","authors":"Karen Lin, Yehao Sun, Rhea Raghu, Parth Suharu, Felix Effah, Irfan Rahman","doi":"10.1016/j.toxrep.2026.102202","DOIUrl":"10.1016/j.toxrep.2026.102202","url":null,"abstract":"<div><div>Hemp-derived cannabinoids (CBDs) such as Δ8- and Δ10-tetrahydrocannabinol (THC) in cannabis e-cigarettes have been growing in popularity among youth, causing great concern for their health effects. Previous novel lung injury outbreaks, such as E-cigarette or Vaping Use-Associated Lung Injury (EVALI), were associated with the rising use of e-cigarettes and vaping products. Toxicological studies have revealed that chronic exposure to cannabis vapor can cause adverse brain and pulmonary effects. Hemp products are classified as cannabis and set a limit of no more than 0.3 % Δ9-THC, while products containing more than 0.3 % are defined as ‘marijuana.’ This has led to the proliferation of hemp-derived intoxicating cannabinoids, such as Δ8- and Δ10-THC, in addition to cannabidiol (CBD), cannabinol (CBN), cannabigerol (CBG), and Δ9-THC appearing in combination products. CBD frequently serves as a significant component of hemp-derived formulations, making it a central consideration for toxicological and regulatory evaluation as well. This phenomenon poses significant health risks to youth because these newer THC isomers and products are currently unregulated and not well-researched, yet they are still widely available. Therefore, we have examined the pharmacology, toxicity, potential therapeutic uses and possible health risks of several THC and hemp-derived cannabinoids. This review draws insightful highlights to the public health consequences of secondary exposures to CBD and THC, and their molecular mechanisms of action. It underscores the urgency for a regulatory oversight over unregulated cannabinoid markets to prevent toxicity of vaping-related health crises and other rapidly emerging cannabis health disorders, like the cannabinoid hyperemesis syndrome (CHS).</div></div>","PeriodicalId":23129,"journal":{"name":"Toxicology Reports","volume":"16 ","pages":"Article 102202"},"PeriodicalIF":0.0,"publicationDate":"2026-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145977347","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}
Pub Date : 2026-01-05DOI: 10.1016/j.toxrep.2026.102200
Julio César Mantilla-Pardo , Juan David García-Valencia , Juan Pablo Fernández-Cubillos
Kambo is a natural secretion obtained from the Amazonian frog Phyllomedusa bicolor, traditionally used in ritualistic and alternative medicine practices for its purported purifying and immunostimulatory effects. Acute intoxication has been associated with neuropsychiatric manifestations, electrolyte disturbances, and systemic complications; however, involvement of the peripheral nervous system has not been previously confirmed by electrodiagnostic studies. We report the case of a 40-year-old man with no prior medical history who developed rapidly progressive quadriparesis and facial diparesis four days after subcutaneous self-application of Kambo venom. Cerebrospinal fluid analysis demonstrated albuminocytologic dissociation, and nerve conduction studies revealed an acute demyelinating motor polyneuropathy with conduction block and preserved sensory conduction. Due to clinical deterioration and risk of respiratory failure, the patient required intensive care management. He initially underwent five sessions of plasmapheresis with limited improvement, followed by intravenous immunoglobulin at a dose of 0.4 g/kg/day for five days, resulting in partial neurological recovery. At three-month follow-up, he persisted with residual motor deficits without sensory involvement. This case represents, to our knowledge, the first electrodiagnostically confirmed report of acute polyneuropathy associated with Kambo poisoning. Clinicians should be aware that Kambo intoxication may extend beyond central neuropsychiatric effects to involve the peripheral nervous system, and early recognition with consideration of immunomodulatory therapy may be warranted.
{"title":"Acute polyneuropathy associated with Kambo poisoning: An unusual case report","authors":"Julio César Mantilla-Pardo , Juan David García-Valencia , Juan Pablo Fernández-Cubillos","doi":"10.1016/j.toxrep.2026.102200","DOIUrl":"10.1016/j.toxrep.2026.102200","url":null,"abstract":"<div><div>Kambo is a natural secretion obtained from the Amazonian frog Phyllomedusa bicolor, traditionally used in ritualistic and alternative medicine practices for its purported purifying and immunostimulatory effects. Acute intoxication has been associated with neuropsychiatric manifestations, electrolyte disturbances, and systemic complications; however, involvement of the peripheral nervous system has not been previously confirmed by electrodiagnostic studies. We report the case of a 40-year-old man with no prior medical history who developed rapidly progressive quadriparesis and facial diparesis four days after subcutaneous self-application of Kambo venom. Cerebrospinal fluid analysis demonstrated albuminocytologic dissociation, and nerve conduction studies revealed an acute demyelinating motor polyneuropathy with conduction block and preserved sensory conduction. Due to clinical deterioration and risk of respiratory failure, the patient required intensive care management. He initially underwent five sessions of plasmapheresis with limited improvement, followed by intravenous immunoglobulin at a dose of 0.4 g/kg/day for five days, resulting in partial neurological recovery. At three-month follow-up, he persisted with residual motor deficits without sensory involvement. This case represents, to our knowledge, the first electrodiagnostically confirmed report of acute polyneuropathy associated with Kambo poisoning. Clinicians should be aware that Kambo intoxication may extend beyond central neuropsychiatric effects to involve the peripheral nervous system, and early recognition with consideration of immunomodulatory therapy may be warranted.</div></div>","PeriodicalId":23129,"journal":{"name":"Toxicology Reports","volume":"16 ","pages":"Article 102200"},"PeriodicalIF":0.0,"publicationDate":"2026-01-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145926066","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}
Pub Date : 2026-01-02DOI: 10.1016/j.toxrep.2026.102199
Cherdsak Boonyong , Pannapa Powthong
Imidacloprid is frequently detected as a residue in food commodities, raising concerns about potential human health risks. Previous findings remain fragmented, and no study has systematically elucidated the primary human target organs and underlying mechanisms using an integrative systems toxicology framework. We applied a human-specific network toxicology approach to characterize imidacloprid-induced toxicity comprehensively. By integrating target prediction and ADME/toxicity models (ADMETlab 3.0, admetSAR 3.0, and ProTox 3.0), the study identified three primary human-relevant toxicity endpoints (respiratory toxicity, liver injury, and genotoxicity/carcinogenicity). Protein-protein interaction, GO, and KEGG pathway analyses revealed that MAPK, NF-κB, JAK-STAT, UPR-ER stress, and Wnt signaling networks may be key pathways involved in oxidative stress, inflammatory signaling, cell-cycle dysregulation, and apoptosis. Molecular docking analysis further supported relatively stronger predicted binding of imidacloprid to several upstream regulatory proteins, including PTGS2 (COX-2), NOS3 (eNOS), APC, CDH1 (cadherin-1 or E-cadherin), AR, HSPA5 (GRP78 or BiP), HSP90AA1 (HSP90α), JAK2, and RELA (p65), whereas downstream signaling proteins such as MAPK14 (p38α), MAPK1 (ERK2), MAPK3 (ERK1), NFKB1 (p50/p105), WNT3A (Wnt), TNF (TNF-α), ESR1 (ERα), and BCL2 exhibited moderate predicted binding. Although these findings are derived from computational analyses and do not establish functional disruption, the coordinated involvement of upstream and downstream signaling hubs suggests possible mechanisms through which imidacloprid exposure may influence multiple organ systems. Taken together, this study provides a systems-level, hypothesis-generating framework to support future experimental validation and human health risk assessment.
{"title":"Prediction of primary human targets and toxicity mechanisms of imidacloprid using integrative In Silico approaches","authors":"Cherdsak Boonyong , Pannapa Powthong","doi":"10.1016/j.toxrep.2026.102199","DOIUrl":"10.1016/j.toxrep.2026.102199","url":null,"abstract":"<div><div>Imidacloprid is frequently detected as a residue in food commodities, raising concerns about potential human health risks. Previous findings remain fragmented, and no study has systematically elucidated the primary human target organs and underlying mechanisms using an integrative systems toxicology framework. We applied a human-specific network toxicology approach to characterize imidacloprid-induced toxicity comprehensively. By integrating target prediction and ADME/toxicity models (ADMETlab 3.0, admetSAR 3.0, and ProTox 3.0), the study identified three primary human-relevant toxicity endpoints (respiratory toxicity, liver injury, and genotoxicity/carcinogenicity). Protein-protein interaction, GO, and KEGG pathway analyses revealed that MAPK, NF-κB, JAK-STAT, UPR-ER stress, and Wnt signaling networks may be key pathways involved in oxidative stress, inflammatory signaling, cell-cycle dysregulation, and apoptosis. Molecular docking analysis further supported relatively stronger predicted binding of imidacloprid to several upstream regulatory proteins, including PTGS2 (COX-2), NOS3 (eNOS), APC, CDH1 (cadherin-1 or E-cadherin), AR, HSPA5 (GRP78 or BiP), HSP90AA1 (HSP90α), JAK2, and RELA (p65), whereas downstream signaling proteins such as MAPK14 (p38α), MAPK1 (ERK2), MAPK3 (ERK1), NFKB1 (p50/p105), WNT3A (Wnt), TNF (TNF-α), ESR1 (ERα), and BCL2 exhibited moderate predicted binding. Although these findings are derived from computational analyses and do not establish functional disruption, the coordinated involvement of upstream and downstream signaling hubs suggests possible mechanisms through which imidacloprid exposure may influence multiple organ systems. Taken together, this study provides a systems-level, hypothesis-generating framework to support future experimental validation and human health risk assessment.</div></div>","PeriodicalId":23129,"journal":{"name":"Toxicology Reports","volume":"16 ","pages":"Article 102199"},"PeriodicalIF":0.0,"publicationDate":"2026-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145925978","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}
Zearalenone (ZEN), an estrogenic mycotoxin produced by Fusarium species, poses persistent challenges to food and feed safety due to its potent toxicological effects and widespread occurrence in cereal-based products. This study investigated the protective efficacy of activated carbon (AC) derived from pistachio shells, an abundant agricultural by-product against ZEN-induced toxicity in mice. Pistachio shell carbon was prepared through chemical activation and comprehensively characterized using SEM, FTIR spectroscopy, and BET surface area analysis. Activation increased surface area from 4.1 to 275.9 m²/g and enhanced pore volume from 0.009 to 0.26 cm³/g, confirming substantial improvements in adsorptive architecture. Forty BALB/c mice were assigned to four dietary treatments: control, ZEN-contaminated diet, and ZEN diets supplemented with non-activated or activated carbon (0.5 g/kg). ZEN exposure markedly reduced weight gain, feed intake, antioxidant enzyme activity (GPx, SOD, CAT), and jejunal villus morphology, while elevating serum ALT, AST, and ALP activities. Supplementation with activated carbon significantly ameliorated these adverse effects, restoring growth performance, improving antioxidant status, normalizing liver enzymes, and enhancing intestinal integrity. Histopathological observations corroborated reduced mucosal damage in AC-treated mice. These findings demonstrate that pistachio shell–based activated carbon is a potent, sustainable, and low-cost mycotoxin adsorbent capable of mitigating ZEN toxicity. The study highlights a promising strategy for simultaneous agricultural waste valorization and enhancement of food and feed safety systems.
{"title":"Activated carbon from pistachio shells: A promising approach to improve health metrics in mice with zearalenone exposure","authors":"Faezeh Oskoueian , Kimia Asadi , Zeinab Javanshir , Saeed Heidarisani , Samira Bozorgi Kasgari , Helia Ghafaripour , Ehsan Karimi , Ehsan Oskoueian","doi":"10.1016/j.toxrep.2025.102197","DOIUrl":"10.1016/j.toxrep.2025.102197","url":null,"abstract":"<div><div>Zearalenone (ZEN), an estrogenic mycotoxin produced by Fusarium species, poses persistent challenges to food and feed safety due to its potent toxicological effects and widespread occurrence in cereal-based products. This study investigated the protective efficacy of activated carbon (AC) derived from pistachio shells, an abundant agricultural by-product against ZEN-induced toxicity in mice. Pistachio shell carbon was prepared through chemical activation and comprehensively characterized using SEM, FTIR spectroscopy, and BET surface area analysis. Activation increased surface area from 4.1 to 275.9 m²/g and enhanced pore volume from 0.009 to 0.26 cm³/g, confirming substantial improvements in adsorptive architecture. Forty BALB/c mice were assigned to four dietary treatments: control, ZEN-contaminated diet, and ZEN diets supplemented with non-activated or activated carbon (0.5 g/kg). ZEN exposure markedly reduced weight gain, feed intake, antioxidant enzyme activity (GPx, SOD, CAT), and jejunal villus morphology, while elevating serum ALT, AST, and ALP activities. Supplementation with activated carbon significantly ameliorated these adverse effects, restoring growth performance, improving antioxidant status, normalizing liver enzymes, and enhancing intestinal integrity. Histopathological observations corroborated reduced mucosal damage in AC-treated mice. These findings demonstrate that pistachio shell–based activated carbon is a potent, sustainable, and low-cost mycotoxin adsorbent capable of mitigating ZEN toxicity. The study highlights a promising strategy for simultaneous agricultural waste valorization and enhancement of food and feed safety systems.</div></div>","PeriodicalId":23129,"journal":{"name":"Toxicology Reports","volume":"16 ","pages":"Article 102197"},"PeriodicalIF":0.0,"publicationDate":"2025-12-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145925977","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}
Pub Date : 2025-12-23DOI: 10.1016/j.toxrep.2025.102194
Majid Farhadi , Behrouz Beiranvand
Heavy metals (HMs) bonded to PM (Particulate Matter) are a significant component of rural air pollution. They're primarily released from fossil fuel combustion and the operational decay of automobiles, leading to their considerable presence in roadway dust. This study aims to examine the concentration and seasonal effects on HM emissions in rural air. The pooled mean concentrations for As (7.81 ng m-³), Cd (4.42 ng m-³), and Pb (60.97 ng m-³) were statistically significant. Pb concentrations were exceptionally high in some rural areas of China, with mean values over 500 ng m-³ reported in two studies. Studies showed notably high levels of Pb, Cu, and Zn, with some sites having exceptional concentrations. The analysis also found significant seasonal variations, with many HMs showing higher concentrations in winter, which is likely due to increased coal combustion for heating. Seasonal analysis in China revealed higher concentrations of several HMs in winter, likely due to increased coal combustion for heating. In spring, road and soil dust from natural phenomena such as dust storms was a primary source of HMs.
与颗粒物（PM）结合的重金属（HMs）是农村空气污染的重要组成部分。它们主要从化石燃料燃烧和汽车的运行衰变中释放出来，导致它们在道路灰尘中大量存在。本研究旨在探讨农村空气中HM排放的浓度和季节效应。砷（7.81 ng m-³）、镉（4.42 ng m-³）和铅（60.97 ng m-³）的混合平均浓度具有统计学意义。中国一些农村地区的铅浓度异常高，两项研究报告的平均值超过500 ng m-³。研究表明，铅、铜和锌的含量明显偏高，有些地方的浓度异常。分析还发现了显著的季节变化，许多HMs在冬季浓度较高，这可能是由于取暖用煤燃烧增加。中国的季节分析显示，几种HMs的浓度在冬季较高，可能是由于取暖用煤燃烧增加。在春季，沙尘暴等自然现象产生的道路和土壤粉尘是HMs的主要来源。
{"title":"A meta-analysis on particulate matter-associated heavy metals in rural air: Concentration, seasonal variability, and pollution sources","authors":"Majid Farhadi , Behrouz Beiranvand","doi":"10.1016/j.toxrep.2025.102194","DOIUrl":"10.1016/j.toxrep.2025.102194","url":null,"abstract":"<div><div>Heavy metals (HMs) bonded to PM (Particulate Matter) are a significant component of rural air pollution. They're primarily released from fossil fuel combustion and the operational decay of automobiles, leading to their considerable presence in roadway dust. This study aims to examine the concentration and seasonal effects on HM emissions in rural air. The pooled mean concentrations for As (7.81 ng m<sup>-</sup>³), Cd (4.42 ng m<sup>-</sup>³), and Pb (60.97 ng m<sup>-</sup>³) were statistically significant. Pb concentrations were exceptionally high in some rural areas of China, with mean values over 500 ng m<sup>-</sup>³ reported in two studies. Studies showed notably high levels of Pb, Cu, and Zn, with some sites having exceptional concentrations. The analysis also found significant seasonal variations, with many HMs showing higher concentrations in winter, which is likely due to increased coal combustion for heating. Seasonal analysis in China revealed higher concentrations of several HMs in winter, likely due to increased coal combustion for heating. In spring, road and soil dust from natural phenomena such as dust storms was a primary source of HMs.</div></div>","PeriodicalId":23129,"journal":{"name":"Toxicology Reports","volume":"16 ","pages":"Article 102194"},"PeriodicalIF":0.0,"publicationDate":"2025-12-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145926064","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}
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