Toxicology Reports最新文献

{"title":"Naringin ameliorates high-fat diet-induced hepatotoxicity and dyslipidemia in experimental rat model via modulation of anti-oxidant enzymes, AMPK and SERBP-1c signaling pathways.","authors":"Sweata Sarkar, Sanjib Ghosh, Maharaj Biswas","doi":"10.1016/j.toxrep.2025.102062","DOIUrl":"10.1016/j.toxrep.2025.102062","url":null,"abstract":"<p><p>High-fat diet causes elevation of steatosis, dyslipidemia and oxidative stress which eventually leads to hepatic injury in the form of non-alcoholic fatty liver disease (NAFLD). Naringin, a natural flavonoid, having tremendous potentiality including antioxidant, anti-inflammatory, hypolipidemic role. Based on this proposition, we investigated the role of naringin in hepatotoxicity and its possible underlying mechanism caused by high-fat diet for prolonged time. Fifteen Wistar rats were divided into three groups: Group A (CON) received normal diet; Group B (HFD) was administered with high-fat diet for 16 weeks; and Group C (THN) was treated with naringin (100 mg/kg B.W.) for last 6 weeks after induction of obesity. After autopsy, various parameters were studied like gravimetry, serum biochemistry, ROS activity, anti-oxidant enzymes, genes expression (AMPK and SREBP-1C), histochemistry, histopathology and ultrastructure of hepatic tissue. In HFD group, Masson's trichome stain intensity increased 6.8-folds, indicating the onset of liver fibrosis; ROS generation and lipid peroxidation (TBARS) were significantly (p < 0.01) increased, whereas SOD and CAT were decreased by 36.7 % and 49.7 %, respectively. Furthermore, these parameters were remained normal in THN group. Besides, HFD group displayed extreme elevation in hepatic SREBP-1C expression (147 %) and downregulation of AMPK gene (77 %) compared to control. The ultrastructural study revealed most important and new insight of this study where HFD induced extreme reticule stress in hepatic tissue which was significantly improved by the treatment of naringin. These findings demonstrate that the naringin may be used as a potential therapeutic agent to combat obesity related hyperlipidemia and NAFLD.</p>","PeriodicalId":23129,"journal":{"name":"Toxicology Reports","volume":"14 ","pages":"102062"},"PeriodicalIF":0.0,"publicationDate":"2025-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12167040/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144302897","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":"Assembled human microbiome and metabolome in chronic kidney disease: Dysbiosis a double-edged sword interlinking Circ-YAP1, Circ-APOE & Circ-SLC8A1.","authors":"Eman A Zaki, Sherif M Afifi, Naglaa M Ammar, Mai O Kadry","doi":"10.1016/j.toxrep.2025.102058","DOIUrl":"10.1016/j.toxrep.2025.102058","url":null,"abstract":"<p><p>Dysbiosis is an alteration in microbiota diversity previously elucidated in patients with chronic kidney disease (CKD). Relationship between dysbiosis and CKD is bidirectional; Uremic milieu disturbs the human microbiota on the other hand, gut metabolites influence CKD development. As a result, we outline the possible contribution of microbiota in the pathophysiology, diagnosis and monitoring of CKD. A growing body of research indicates that changes in circular RNAs (circ-RNAs) were observed in CKD with pathogenic implications, including modifying intracellular signaling, exaggerating oxidative stress, cellular apoptosis and inflammation. Additionally, Circ-RNAs exhibit promising role in clinical settings for monitoring, diagnosis, prognostication, and treatment of CKD. Herein blood samples were collected from 60 Egyptian patients with CKD as well as 60 healthy volunteers who served as controls. Following clinical evaluations, OPLS-DA and PCA GC-MS analysis were performed to detect metabolite perturbations. The levels of toxic uremic metabolites, such as urea, hexanedioic acid, ribonic acid, dodecanoic acid, pyrimidine, 1H-indole, 1H-indole-3-acetic acid, butanoic acid, L-cystine, and benzaldehyde linked to renal fibrosis were found to be elevated. Conversely, Reno-protective metabolites, such as short-chain fatty acids; 1H-indole were found to be negatively correlated with indole propionic acid, acetic acid, 2-propenoic acid, tryptophan, tyrosine, and glucitol (AUC 0.65) derived from the gut flora. CKD patients clarified an alteration both gene and protein expression of circRNAs (Circ-YAP1, circ-APOE, and circ-SLC8A1)/mTOR. Moreover, these biomarkers had a significant correlation with clinical investigations such as Creatinine, Glomerular filtration rate (GFR) and albumin/Creatinine (A/C) ratio. These results shed some light on the metabolic biomarkers that are associated with CKD and novel insights into metabolomics/microbiota/Circ-YAP1/circ-APOE/circ-SLC8A1/mTOR interlinked with disease prognosis/diagnosis that could be translated into clinically relevance.</p>","PeriodicalId":23129,"journal":{"name":"Toxicology Reports","volume":"14 ","pages":"102058"},"PeriodicalIF":0.0,"publicationDate":"2025-05-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12163407/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144302894","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":"Human health risks of heavy metals contamination of a water-soil-vegetables farmland system in Toke Kutaye of West Shewa, Ethiopia.","authors":"Getacho Feyisa, Birhanu Mekassa, Lemessa B Merga","doi":"10.1016/j.toxrep.2025.102061","DOIUrl":"10.1016/j.toxrep.2025.102061","url":null,"abstract":"<p><p>Contamination of foods with heavy metals poses significant threats to human health. In this study, human health risks of heavy metals contaminated vegetables (cabbage, onion and green pepper) from irrigation farmlands in Toke Kutaye, Ethiopia were evaluated. Wet acid digestion of vegetables, supporting soil and irrigation water samples were employed prior to FAAS determination of heavy metals (Fe, Zn, Cu, Mn, Co, Cr, Ni, Cd and Pb). The measured average values of the studied heavy metals ranged from < 0.01-2.52 ± 0.06 mg/L, 2.25 ± 0.19-131.31 ± 0.13 mg/kg, and < 0.01-18.21 ± 0.17 mg/kg for water, soil and vegetable samples, respectively. The average concentration of the studied heavy metals in the vegetable samples were arranged in the order of Zn>Cu>Fe>Mn>Co>Ni>Pb>Cr>Cd. The heavy metals accumulation in the vegetables followed the order of cabbage > onion > green pepper. The mean values of Pb in the vegetables exceeded the WHO/FAO guideline value. The possible sources of the heavy metals were agrochemicals, domestic sewage wastes, manures and geogenic processes. The hazard quotient (HQ) and hazard index (HI) based human health risk assessment results indicated that the individual metals and their mixture could pose insignificant non-carcinogenic risk (HQ and HI < 1) to consumers. However, cancer risk assessment values for the individual Ni metal, and the mixture of Ni, Cr and Pb exceeded the threshold limit for both children and adults. These results highlight possible chronic carcinogenic risks due to exposure to heavy metals via consumption of contaminated vegetables from the study area, which requires the concern of the consumers and regulatory bodies.</p>","PeriodicalId":23129,"journal":{"name":"Toxicology Reports","volume":"14 ","pages":"102061"},"PeriodicalIF":0.0,"publicationDate":"2025-05-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12163411/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144302896","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 rs140668532 SNP in GSK-3β gene as a potential biomarker for Alzheimer's disease: Insights from computational modeling.","authors":"İrem Gülfem Albayrak, Belkıs Atasever Arslan","doi":"10.1016/j.toxrep.2025.102060","DOIUrl":"10.1016/j.toxrep.2025.102060","url":null,"abstract":"<p><p>Glycogen synthase kinase-3 beta (GSK-3β) is well recognized for its role in diverse physiological processes, including apoptosis, mitochondrial function, and gene transcription regulation. The precise regulation of GSK-3β activity is critical for maintaining neuronal health, and dysregulation may result in disturbances in neurological functions. Polymorphisms in the GSK-3β gene may increase susceptibility to neurodegenerative disorders. To assess the structural and functional consequences of deleterious SNPs in GSK-3β, various in silico approaches was utilized. Analysis identified 27 deleterious SNPs in the GSK-3β gene, among which 10 were classified as damaging by SIFT, PolyPhen-2, and MutPred2. The Project Hope software simulated ten harmful mutations in the GSK-3β gene. The pathways associated with neurodegeneration involving the GSK-3β gene and its interacting genes were identified through the KEGG and GeneMANIA databases, respectively. The V317F mutation was shown to reduce GSK-3β inhibition by highly selective inhibitory ligand PF04802367 (PF-367) and impair the GSK-3β-Tau interaction. The influence of GSK3β on Aβ formation suggests that the V317F mutation has a tau-independent neurodegenerative impact. The experimental investigation of the V317F mutant GSK-3β's effect on neurodegeneration may enhance the understanding of the biomarker potential of rs140668532 in Alzheimer's disease.</p>","PeriodicalId":23129,"journal":{"name":"Toxicology Reports","volume":"14 ","pages":"102060"},"PeriodicalIF":0.0,"publicationDate":"2025-05-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12163410/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144302898","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":"Drugs or dissection? Unraveling a diagnostic puzzle in the ED: A case report on Tizanidine-Nifedipine interaction.","authors":"Muhammad Abd Ur Rehman, Maaz Uddin Mohammed, Muhammad Abdul Mannan, Waleed Salem","doi":"10.1016/j.toxrep.2025.102055","DOIUrl":"10.1016/j.toxrep.2025.102055","url":null,"abstract":"<p><p>Lower back pain is among the top ten reasons patients visit the emergency department (ED). Tizanidine, a centrally acting alpha-2 adrenergic receptor agonist, is commonly prescribed for managing spasticity in patients with cerebral or spinal injuries. It is also used as an effective treatment for nonspecific lower back pain. One of the most critical and life-threatening causes of lower back pain is abdominal aortic dissection, particularly in patients with hypertension. Nifedipine, a 1,4-dihydropyridine calcium channel blocker (CCB), is a widely used oral antihypertensive and antianginal agent. It lowers systemic vascular resistance and dilates coronary arteries by inhibiting calcium ion (Ca²⁺) entry into the smooth muscle cells of small arteries (arterioles), thereby reducing systemic blood pressure and improving myocardial oxygen delivery. We report a compelling case of a male patient presenting to the ED with high blood pressure and lower back pain. Shortly after the administration of tizanidine and nifedipine, his blood pressure dropped significantly within an hour. Initially suspected to be a ruptured abdominal aortic dissection, the cause was later identified as a drug-drug interaction. The synergistic effects of tizanidine and nifedipine resulted in a rapid and critical drop in blood pressure. The Drug Interaction Probability Scale (DIPS) score of 4 suggests the hypotensive episode was possibly caused by a drug interaction. This case also highlights the importance of point of care ultrasound (POCUS) and repeated examinations in excluding life-threatening conditions like aortic rupture.</p>","PeriodicalId":23129,"journal":{"name":"Toxicology Reports","volume":"14 ","pages":"102055"},"PeriodicalIF":0.0,"publicationDate":"2025-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12163400/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144302895","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":"Analysis of pesticide residues in tomatoes from the tomato field and markets of KPK, Pakistan and their potential risk to human health.","authors":"Syeda Nazish-Ali, Nazia Rafique, Touqeer Taj, Saif Ullah, Farrakh Mehboob","doi":"10.1016/j.toxrep.2025.102059","DOIUrl":"10.1016/j.toxrep.2025.102059","url":null,"abstract":"<p><p>The study was designed to get a real time picture of pesticide residues in tomato samples from the fields of two districts of Khyber Pakhtunkhwa and the markets of Islamabad, Pakistan. A citrate buffered QuEChERS method was validated for forty-nine multiclass pesticides belonging to carbamates, neonicotinoids, organophosphates, pyrethroids, triazines and triazoles on LC-MS/MS. The method's limits of detection and the quantification with the validated method ranged from 0.001 to 0.01 mg/kg and 0.01-0.1 mg/kg, respectively. Fifty one samples were analyzed with the validated method, and 58.8 % (n = 30) of the analyzed samples were found contaminated. Out of these contaminated samples, 83.3 % (n-25) were field samples, and 16.7 % (n = 5) were market samples. Four (7.8 %) field samples were found non-compliant with the European Union's Maximum Residue Limits (EU-MRLs). The frequently detected pesticides were imidacloprid and tebuconazole. Thiamethoxam, tebuconazole, pyraclostrobin, metalaxyl, and chlorpyrifos, were the pesticides that exceeded the EU-MRLs. The residues of detected pesticides were found to pose a very low health risk to consumers.</p>","PeriodicalId":23129,"journal":{"name":"Toxicology Reports","volume":"14 ","pages":"102059"},"PeriodicalIF":0.0,"publicationDate":"2025-05-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12171806/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144317920","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":"Protective effect of omega-3 on reducing doxorubicin toxicity in preclinical trials.","authors":"Marcelo Henrique de Paiva, Silvio de Almeida-Junior, Cristiane Buzatto Garcia, Poliana Marques Pereira, João Guilherme Martins, Flávio Henrique Rodrigues Stante, Tiago Machado Carneiro Lucera, Fernanda Gosuen Gonçalves Dias, Ricardo Andrade Furtado, Daniel Paulino Junior","doi":"10.1016/j.toxrep.2025.102056","DOIUrl":"10.1016/j.toxrep.2025.102056","url":null,"abstract":"<p><p>The use of chemotherapeutic agents, such as doxorubicin, is often associated with severe adverse effects, making it essential to develop therapeutic strategies that can attenuate or reduce their toxicity. This study aimed to investigate the effects of omega-3 in mitigating the damage induced by doxorubicin. Rabbits received doxorubicin (1 mg/kg, twice weekly for six weeks) with or without omega-3 (500, 1000, or 2000 mg/kg), administered concomitantly. An additional group received omega-3 alone (2000 mg/kg). Hematological, biochemical, genotoxic (micronucleus assay), cardiological (electrocardiogram, echocardiogram, and markers), and histopathological parameters were assessed. Os resultados mostraram que o tratamento com doxorrubicina isolada induziu caquexia nos animais. O tratamento com ômega-3 melhora parâmetros como ganho de peso, fração de ejeção cardíaca, encurtamento sistólico ventricular, marcadores cardíacos CK-MB e Troponina I, área do ventrículo esquerdo e parâmetros histopatológicos (inflamação, edema, dano celular e fibras musculares), sugerindo um efeito protetor. Além disso, o ômega-3 exibiu atividade antigenotóxica, evidenciada pela redução de micronúcleos. Esses achados indicam que o ômega-3 pode servir como um complemento eficaz à quimioterapia, reduzindo a toxicidade da doxorrubicina.</p>","PeriodicalId":23129,"journal":{"name":"Toxicology Reports","volume":"14 ","pages":"102056"},"PeriodicalIF":0.0,"publicationDate":"2025-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12159444/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144286537","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":"Unveiling the molecular interactions between bisphenol A and the cell surface Toll-like receptors: Implications for immune health.","authors":"Prem Rajak, Abhratanu Ganguly","doi":"10.1016/j.toxrep.2025.102057","DOIUrl":"10.1016/j.toxrep.2025.102057","url":null,"abstract":"<p><p>Microplastic pollution is an emerging threat to the human health. In nature, microplastics release several compounds of toxicological importance. Among them, bisphenol A (BPA), a widely used additive in plastic production, is an important one. Upon breakdown, microplastics release significant amounts of BPA in air, water, and soil. Humans may be exposed to BPA through nasal, oral, and dermal routes. BPA is linked to oxidative stress, physiological disturbance, and chronic diseases. Moreover, it may target the immune system. Toll-like receptors (TLRs) are important mediators of both innate and adaptive immunity and recognize microbial signature molecules to trigger signaling cascades employed in anti-microbial defense mechanism. Inhibition of TLR-mediated signaling can result in compromised immunity. Hence, the present work aims to investigate the inhibitory potential of BPA against cell surface TLRs. For this study, a molecular docking approach using the AutoDock vina algorithm was employed to analyze the docking potential of BPA with the surface-associated TLRs. Results have revealed that BPA binds to TLR1, TLR2, TLR4, TLR5, and TLR6 with affinity ranging from -4.3 to -7.3 kcal/mol. Structural analyses of the docked complexes have suggested that BPA binds to TLR through conventional H-bonds. Van der Waals and other hydrophobic interactions further stabilized the docked complexes. Notably, C-H bonds were also apparent in some docked conformations. Hence, results of the present study equivocally suggest that BPA can potentially bind to the cell surface TLRs through various bonds and interactions. Such interactions may modulate TLR-mediated signaling and immunity in organisms.</p>","PeriodicalId":23129,"journal":{"name":"Toxicology Reports","volume":"14 ","pages":"102057"},"PeriodicalIF":0.0,"publicationDate":"2025-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12163412/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144302899","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":"Comparative pharmacological analysis of fam-trastuzumab deruxtecan-nxki and sacituzumab govitecan-hziy: Two recently developed chemotherapies in the crucial battle against breast cancer.","authors":"Amjad Z Alrosan, Isra Dmour, Aseel O Rataan, Ghaith B Heilat, Khaled Alrosan","doi":"10.1016/j.toxrep.2025.102054","DOIUrl":"10.1016/j.toxrep.2025.102054","url":null,"abstract":"<p><p>This study provides a detailed pharmacological evaluation of the recently approved antibody-drug conjugates (ADCs), fam-trastuzumab deruxtecan-nxki and sacituzumab govitecan-hziy, focusing on their adverse event (AE) profiles post-approval by the United States Food and Drug Administration (US FDA) for breast cancer (BC) treatment. By assessing their safety profiles, this study aims to provide clinically relevant insights into their impact and highlight the necessity for ongoing post-marketing surveillance. AE data were extracted from the US FDA's Adverse Event Reporting System (FAERS) (2019-2023), focusing on reports filed after each drug's approval, and descriptive statistical methods were used to classify and compare AE frequencies for both therapies. FAERS recorded eight AEs for fam-trastuzumab deruxtecan-nxki and thirteen for sacituzumab govitecan-hziy, despite the latter's later approval. AEs linked to fam-trastuzumab deruxtecan-nxki were musculoskeletal and infection-related, while sacituzumab govitecan-hziy showed broader systemic effects (musculoskeletal, gastrointestinal, cardiovascular, and dermatological). One patient receiving fam-trastuzumab deruxtecan-nxki experienced elevated ALT levels, suggesting potential hepatic involvement. While both therapies demonstrate therapeutic promise, continuous safety monitoring is essential. The FAERS dataset's demographic limitations highlight the need for more comprehensive post-marketing surveillance to assess long-term AE risks and optimize BC treatment safety.</p>","PeriodicalId":23129,"journal":{"name":"Toxicology Reports","volume":"14 ","pages":"102054"},"PeriodicalIF":0.0,"publicationDate":"2025-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12152638/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144276002","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":"Combined vitamin D and coconut oil are promising protective approaches against aluminum-induced testicular damage in rats.","authors":"Fatma A Al-Nefeiy","doi":"10.1016/j.toxrep.2025.102051","DOIUrl":"10.1016/j.toxrep.2025.102051","url":null,"abstract":"<p><p>Exposure to high levels of aluminum (Al) is a widespread environmental problem where its use is continuously increasing. Al may play a substantial role in male fertility decline. This study was designed experimentally in rats to explore the protective effect of both vitamin D (VD) and virgin coconut oil (VCO) against aluminum chloride (AlCl₃) on the biochemical and histopathological changes of the testis. Male rats were divided into 7 groups: Control group, VD group, VCO group, AlCl3-treated group, AlCl3 co-treated with VD group, AlCl3 co-treated with VCO group, AlCl₃ co-treated with both VD and VCO group. After six weeks of treatment, the rats of each group were sacrificed where blood and testicular samples were assembled and processed for different biochemical and histopathological studies. The results showed that AlCl₃ reduced body weight gain, testis weights, reproductive hormones (FSH, LH, testosterone), and antioxidant enzymes (SOD, GPx, CAT), while elevating oxidative stress (MDA). These effects were notably reversed by VD, VCO, or their combination, with combined therapy showing the greatest improvement. Histologically, AlCl₃ caused severe testicular damage, including disrupted seminiferous tubules, degenerated spermatogenic cells, interstitial fibrosis, and Leydig cell loss, findings partially restored by VD or VCO and nearly normalized with their combination. Immunohistochemistry further confirmed these improvements, with combined treatment reducing caspase-3 (apoptosis) and restoring Ki-67 (proliferation) expression. In conclusion, AlCl₃ exposure impaired testicular function by disrupting hormone levels, antioxidant defenses, and tissue integrity. VD and VCO, especially in combination, effectively counteracted these effects, restoring hormonal balance, antioxidant status, and normal tissue structure with reducing apoptosis and enhancing proliferation. Collectively, these findings suggest that VD and VCO synergistically counteract AlCl₃-induced testicular toxicity, offering anti-inflammatory, antioxidant, anti-apoptotic, and proliferative mechanisms.</p>","PeriodicalId":23129,"journal":{"name":"Toxicology Reports","volume":"14 ","pages":"102051"},"PeriodicalIF":0.0,"publicationDate":"2025-05-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12152672/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144276001","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}