{"title":"Comparable hepatocellular metabolomic signatures under glucose and palmitic acid treatment relative to butyrate in relation to metabolic dysfunction-associated fatty liver disease.","authors":"Priyankar Dey","doi":"10.1080/13813455.2025.2500651","DOIUrl":"https://doi.org/10.1080/13813455.2025.2500651","url":null,"abstract":"<p><strong>Introduction: </strong>Among the dietary factors, glucose, and fatty acids are known to trigger fatty liver disease, while butyrate attenuates steatosis.</p><p><strong>Objective: </strong>To decipher the hepatocellular altered metabolome under nutrient perturbation relevant to fatty liver disease.</p><p><strong>Methods: </strong>HepG2 cells were cultured under the influence of sub-lethal doses of glucose, palmitic acid (PA), and butyrate. Following the treatment, intracellular metabolites were extracted and derivatized for GCMS analysis. Chemical class enrichment, metabolic pathway analysis, and metabolomic interactome analysis were undertaken.</p><p><strong>Results: </strong>Glucose, PA and butyrate caused loss of cell viability at 160 mM, 1600 µM, and 40 mM concentration, respectively. A total of 39, 47, 52, and 51 metabolites were identified in control, glucose, PA, and butyrate, respectively, among which 2-ethylhexanoic acid in control and 2-ethylhexan-1-ol in glucose, PA and butyrate were the most abundant metabolites. Pathways related to the mitochondrial electron transport chain were highly enriched in glucose and PA treatments, leading to increased free radicals. The metabolites identified under glucose and PA treatment were linked to the metabolomic markers of metabolic liver diseases.</p><p><strong>Conclusion: </strong>Our data showed that the hepatocellular metabolome of HepG2 cells under glucose and PA treatment is closely related, while the metabolome and pathways associated with butyrate treatment are associated with energy metabolism and alleviation of fatty liver.</p>","PeriodicalId":8331,"journal":{"name":"Archives of Physiology and Biochemistry","volume":" ","pages":"1-11"},"PeriodicalIF":2.5,"publicationDate":"2025-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144075757","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Raoudha Abbassi, Hafsia Bouzenna, Riadh Badraoui, Mohammad Atwan, Faten Brahmi, Anouer Feriani, Arif J Siddiqui, Mohd Adnan, Ahmed Mohajja, Sirine Choura, Mohamed Chamkha, Najla Hfaiedh
{"title":"Heptaminol-induced metabolic liver and cardiac injuries in rats: phytochemical screening, experimental, computational modelling and pharmacological study of <i>phoenix dactylifera</i> seeds.","authors":"Raoudha Abbassi, Hafsia Bouzenna, Riadh Badraoui, Mohammad Atwan, Faten Brahmi, Anouer Feriani, Arif J Siddiqui, Mohd Adnan, Ahmed Mohajja, Sirine Choura, Mohamed Chamkha, Najla Hfaiedh","doi":"10.1080/13813455.2025.2504169","DOIUrl":"https://doi.org/10.1080/13813455.2025.2504169","url":null,"abstract":"<p><p><b>Introduction:</b> Heptaminol (HEP) is widely used and characterized by liver and cardiac risk factors, dysregulated prooxidant-antioxidant balance, and inflammation. This study aimed to study the phytochemical composition of date seeds of <i>Phoenix dactylifera</i> (DSPE) by GC-MS analysis and to assess the <i>in vitro</i> antioxidant, anticoagulant and ACE activities.</p><p><p><b>Methods:</b> The hepato and cardiotoprotective effect against HEP-induced toxicity in rats have been assessed using biochemical, histological and computational assays.</p><p><p><b>Results:</b> HEP increased the body weight, associated significant increases in total cholesterol, triglycerides, total and direct bilirubin, alkaline phosphatase, creatinine kinase-MB, ACE, and troponin-T, exhibited changes in ECG pattern, including ST-segment elevation, and increased rate of TBARS with decreases in the antioxidant enzymatic. DSPE improved these biomarkers alterations through anti-oxidative and anti-coagulant activities, which were confirmed by histopathological examinations. The computational findings supported the in vivo results and showed that DSPE compounds bound Hypoxia-Inducible Factor (HIF-1α) and Insulin-Like Growth Factor (IGF1) with acceptable affinities and molecular interactions.</p><p><p><b>Conclusion:</b> DSPE had hepato and cardioprotective effects against HEP-induced heart and liver injuries. DSPE can be used to prevent acute thrombosis due to its different bioactive compounds.</p>","PeriodicalId":8331,"journal":{"name":"Archives of Physiology and Biochemistry","volume":" ","pages":"1-15"},"PeriodicalIF":2.5,"publicationDate":"2025-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144075758","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Selenium deficiency modulates neonatal pulmonary alveolar development via mitochondrial ROS accumulation and oxidative stress mediated by STAT3 inhibition.","authors":"Hong-Yan Tan, Yao-Lin Xiang, Mei-Juan Tan, Chao-Ce Fang, Ya-Ping Zhang, Fen Peng","doi":"10.1080/13813455.2025.2502451","DOIUrl":"https://doi.org/10.1080/13813455.2025.2502451","url":null,"abstract":"<p><p><b>Context</b>: Recent findings suggest that Selenium (Se) deficiency in neonates may hinder pulmonary alveolar development, but the underlying molecular mechanisms remain underexplored.</p><p><p><b>Objective</b>: This study utilised a neonatal mouse model to investigate the effects of dietary Se deficiency on pulmonary alveolar development.</p><p><p><b>Materials and methods</b>: Techniques such as quantitative PCR, Western blotting, and immunohistochemistry were employed to assess gene and protein expression related to alveolar development and oxidative stress markers. Mitochondrial ROS accumulation was quantified using MitoSOX staining, and the activity of sirtuin 3 (STAT3), a key transcription factor involved in oxidative stress responses, was analysed.</p><p><p><b>Results</b>: Our findings indicate that Se-deficient neonates exhibit significantly impaired alveolar development characterised by reduced alveolar number and surface area. These structural alterations were associated with increased mitochondrial ROS levels and oxidative stress. Furthermore, Se deficiency resulted in decreased STAT3 phosphorylation, suggesting a mechanism whereby Se influences alveolar development through modulation of STAT3 activity and mitochondrial function.</p><p><p><b>Discussion and conclusion</b>: Se plays a critical role in neonatal pulmonary development by modulating oxidative stress and mitochondrial dynamics via the STAT3 pathway. The study underscores the potential of Se supplementation as a strategic intervention to promote alveolar maturation and prevent pulmonary disorders in neonates. Further research is recommended to explore the therapeutic thresholds and timing of Se administration to optimize pulmonary outcomes.</p>","PeriodicalId":8331,"journal":{"name":"Archives of Physiology and Biochemistry","volume":" ","pages":"1-13"},"PeriodicalIF":2.5,"publicationDate":"2025-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144075759","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Cholecalciferol alleviates testicular dysfunction in experimental hyperthyroidism via antioxidant, anti-inflammatory and antiapoptotic effects.","authors":"Heba Rady Salem, Hend Ahmed Kasem","doi":"10.1080/13813455.2025.2503479","DOIUrl":"https://doi.org/10.1080/13813455.2025.2503479","url":null,"abstract":"<p><strong>Background: </strong>This study aimed to investigate the possible protective effect of cholecalciferol against testicular dysfunction in L-thyroxine-induced hyperthyroid rat model.</p><p><strong>Methods: </strong>Twenty-four adult male rats were divided into three groups: control, hyperthyroid, and hyperthyroid cholecalciferol treated. At the end of four weeks, serum samples were collected for measurement of thyroid hormones, testosterone, and serum inflammatory markers (interleukin-6 and tumour necrosis factor-alpha). Thereafter, malondialdehyde and antioxidant enzymes were assessed in the testicular homogenate. Also, histological and immunohistochemical studies of the testicular tissues were done.</p><p><strong>Results: </strong>The current results showed lower serum testosterone and testes weight in hyperthyroid rats than control group, with significantly elevated serum inflammatory markers, and disturbed oxidant/antioxidant status in the testicular tissues. This was associated with structural abnormalities. Immunohistochemical study showed upregulation of caspase-3 and downregulation of proliferating cell nuclear antigen (PCNA) in hyperthyroid rats. Cholecalciferol supplementation significantly improved the testicular dysfunction and the testicular pathological features in the hyperthyroid rats. It significantly decreased the levels of serum inflammatory markers and malondialdehyde levels. Also, cholecalciferol supplementation increased the activity of the antioxidant enzymes in the testicular tissue, downregulated caspase-3 and upregulated PCNA in the testicular tissues.</p><p><strong>Conclusion: </strong>Cholecalciferol could ameliorate pathophysiological changes in rat testes of hyperthyroid rats.</p>","PeriodicalId":8331,"journal":{"name":"Archives of Physiology and Biochemistry","volume":" ","pages":"1-10"},"PeriodicalIF":2.5,"publicationDate":"2025-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143953246","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Zacchaeus S Ololade, Iyadunni A Anuoluwa, Olayinka F Onifade, Adewumi I Adeagbo, Olawumi T Oyebanji, Ademola O Asaju, John C Eze
{"title":"Evaluation of <i>Annona muricata</i> for hepatoprotection, hematological assessment and inhibitor of TGFβR1 in liver diseases.","authors":"Zacchaeus S Ololade, Iyadunni A Anuoluwa, Olayinka F Onifade, Adewumi I Adeagbo, Olawumi T Oyebanji, Ademola O Asaju, John C Eze","doi":"10.1080/13813455.2025.2499840","DOIUrl":"https://doi.org/10.1080/13813455.2025.2499840","url":null,"abstract":"<p><strong>Background: </strong>This study was conducted to assess the hepatoprotective potential of Annona muricata flower (AMF) using albino rats' model.</p><p><strong>Materials and methods: </strong>Liver function assays such as alkaline phosphatase (ALP), alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin (TBILI), antioxidants, haematology (HGB), histology, inhibition of transforming growth factor beta receptor I (TGFβR1) and antibacterial assays were investigated.</p><p><strong>Results and discussion: </strong>Induction with acetaminophen gave rise to a significant increase (p < 0.05) in serum of liver enzymes of ALT, AST, ALP and TBILI in the acetaminophen (APAP) only group, which indicates hepatocellular injury, whereas AMF attenuated liver enzymes level. The histological assessment confirmed that AMF possesses blood-enhancing ability. AMF significantly showed inhibition of TGFβR1. AMF was active against all the tested bacteria with high zones of inhibition.</p><p><strong>Conclusion: </strong>This study provides information on the uses of AMF as a natural product for hepatoprotection and other therapeutic purposes.</p>","PeriodicalId":8331,"journal":{"name":"Archives of Physiology and Biochemistry","volume":" ","pages":"1-18"},"PeriodicalIF":2.5,"publicationDate":"2025-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143960041","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Ji-Hyun Kim, Hyo Jeong Seo, Byeong Wook Noh, Mei Tong He, Yung-Hyun Choi, Eun Ju Cho, Jeong Sook Noh
{"title":"Protective effects of <i>Cuscuta chinensis</i> Lam. extract against learning and memory dysfunction induced by streptozotocin and amyloid β<sub>25-35</sub> <i>in vivo</i> model.","authors":"Ji-Hyun Kim, Hyo Jeong Seo, Byeong Wook Noh, Mei Tong He, Yung-Hyun Choi, Eun Ju Cho, Jeong Sook Noh","doi":"10.1080/13813455.2025.2502861","DOIUrl":"https://doi.org/10.1080/13813455.2025.2502861","url":null,"abstract":"<p><p>Alzheimer's disease (AD) is associated with hyperglycaemia and amyloid beta (Aβ) accumulation. In the present study, we investigated whether an aqueous extract of <i>Cuscuta chinensis</i> Lam. (CCWE) improved cognitive disorder in a hyperglycaemic and cognitive-impaired mouse model. Hyperglycaemia was induced by streptozotocin (STZ, 50 mg/kg) and a single intracerebroventricular injection of Aβ<sub>25-35</sub> (25 nM) was performed. The Aβ<sub>25-35</sub>-injected hyperglycaemic mice were then administered CCWE (100 or 200 mg/kg/day) for 14-d. The protective effects of the CCWE were evaluated by behavioural tests and western blot analysis. The bioactive compounds in CCWE were isolated by UPLC-QTOF/MS analysis. The administration of CCWE improved the learning and memory function in STZ/Aβ<sub>25-35</sub>-injected mice. Moreover, CCWE positively regulated the amyloidogenic pathway-related proteins and insulin signalling-related proteins. The bioactive components in CCWE were also identified. These findings suggest the possibility of CCWE as a potential candidate for the dual-targeting treatment of hyperglycaemia and AD.</p>","PeriodicalId":8331,"journal":{"name":"Archives of Physiology and Biochemistry","volume":" ","pages":"1-13"},"PeriodicalIF":2.5,"publicationDate":"2025-05-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143964563","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Mayra Dias Rodrigues, Brenda Francisconi Diaz, Fernando Henrique Borges, Rhauany Pelisson Guergolette, Larissa Rugila Dos Santos Stopa, Ernane Torres Uchoa, Glaura Scantamburlo Alves Fernandes, Karla Bigetti Guergoletto, Graziela Scalianti Ceravolo
{"title":"Preconceptional treatment with açaí juçara (<i>Euterpe edulis</i> Martius) in advanced-age female rats did not interfere with metabolic parameters and redox balance during pregnancy.","authors":"Mayra Dias Rodrigues, Brenda Francisconi Diaz, Fernando Henrique Borges, Rhauany Pelisson Guergolette, Larissa Rugila Dos Santos Stopa, Ernane Torres Uchoa, Glaura Scantamburlo Alves Fernandes, Karla Bigetti Guergoletto, Graziela Scalianti Ceravolo","doi":"10.1080/13813455.2025.2497260","DOIUrl":"https://doi.org/10.1080/13813455.2025.2497260","url":null,"abstract":"<p><p>The consumption of açaí has been shown to be beneficial to health. This study aimed to evaluate the effects of juçara açai (JU, <i>Euterpe edulis Martius</i>) administration before gestation on the biometric, metabolic, and oxidative status in pregnant rats of advanced maternal age. Healthy female Wistar rats were treated with JU pulp via gavage from postnatal day 168 to 210. After treatment, the rats were mated, and during the 20 days of pregnancy, they were evaluated for body weight (BW), glucose tolerance, adipose tissue and liver weight, the lipid profile, and hepatic oxidative status. At birth, the offspring were weighed and counted. It was observed that JU reduced just maternal glycaemia. The maternal preconceptional treatment did not affect offspring BW. These results suggest that JU could be a safe nutritional intervention during the preconception period in advanced maternal age.</p>","PeriodicalId":8331,"journal":{"name":"Archives of Physiology and Biochemistry","volume":" ","pages":"1-9"},"PeriodicalIF":2.5,"publicationDate":"2025-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143960119","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Hamid Alizadeh, Ahmad Parsaeifar, Roohollah Mohammadi Mirzaei
{"title":"Meteorin-like protein (Metrnl): a key exerkine in exercise-mediated cardiovascular health.","authors":"Hamid Alizadeh, Ahmad Parsaeifar, Roohollah Mohammadi Mirzaei","doi":"10.1080/13813455.2025.2497272","DOIUrl":"https://doi.org/10.1080/13813455.2025.2497272","url":null,"abstract":"<p><strong>Context: </strong>Cardiovascular diseases (CVDs) remain a leading global cause of mortality, necessitating non‑pharmacological interventions such as exercise. Meteorin‑like protein (Metrnl), an exercise‑induced myokine and adipokine, has emerged as a critical mediator of exercise‑mediated cardiovascular benefits, though its specific mechanisms and clinical implications remain underexplored.</p><p><strong>Objective: </strong>This review synthesizes current evidence on Metrnl's role as a key exerkine in cardiovascular health, focusing on its exercise‑induced regulatory mechanisms, tissue‑specific effects, and therapeutic potential for CVD management.</p><p><strong>Methods: </strong>A comprehensive analysis of preclinical and clinical studies was conducted, encompassing molecular, metabolic, and anti‑inflammatory pathways linked to Metrnl. Literature from PubMed, Scopus, and Web of Science was systematically reviewed to evaluate Metrnl's role in exercise‑mediated cardiovascular adaptations.</p><p><strong>Results: </strong>Exercise‑induced Metrnl enhances endothelial function, vascular remodeling, and metabolic regulation via AMPK, PPARγ, and KIT receptor signaling. It promotes glucose/lipid metabolism, angiogenesis, and anti‑inflammatory responses, reducing atherosclerotic risks and improving cardiac repair post‑infarction. Clinically, Metrnl levels correlate with CVD severity, acting as a biomarker for risk stratification. Acute exercise elevates Metrnl, while chronic training effects vary by modality and population. Paradoxically, elevated plasma Metrnl in acute cardiac events predicts adverse outcomes, whereas reduced levels in chronic conditions (e.g., diabetes, heart failure) reflect metabolic dysregulation.</p><p><strong>Discussion: </strong>Metrnl bridges exercise benefits to cardiovascular health through inter‑organ crosstalk, yet discrepancies exist in its chronic exercise‑mediated regulation. Its dual role as a protective mediator and stress‑responsive biomarker underscores context‑dependent interpretations. Unresolved questions include receptor specificity, tissue autonomy, and therapeutic delivery strategies.</p><p><strong>Conclusion: </strong>Metrnl is a pivotal exerkine with promising diagnostic and therapeutic potential for CVDs. Translating its exercise‑mediated benefits into clinical applications requires further human trials to validate mechanisms and optimize interventions. Harnessing Metrnl could revolutionize strategies for CVD prevention and rehabilitation, leveraging exercise's molecular advantages.</p>","PeriodicalId":8331,"journal":{"name":"Archives of Physiology and Biochemistry","volume":" ","pages":"1-15"},"PeriodicalIF":2.5,"publicationDate":"2025-04-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143966131","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Miran M Harhash, Amr A Zahra, Omayma O Abdelaleem, Nermeen A Fouad, Hassan S El Sayed
{"title":"Serum levels of miR-34, miR-182 and miR-378 as novel diagnostic biomarkers in Behçet patients and their relation to disease activity and severity.","authors":"Miran M Harhash, Amr A Zahra, Omayma O Abdelaleem, Nermeen A Fouad, Hassan S El Sayed","doi":"10.1080/13813455.2025.2497266","DOIUrl":"https://doi.org/10.1080/13813455.2025.2497266","url":null,"abstract":"<p><strong>Background: </strong>Behçet Disease (BD) is a chronic multi-systemic vasculitis of relapsing and remitting nature. Many recent studies have denoted the role of micro RNAs (MiRNAs) in the pathogenesis of BD.</p><p><strong>Subjects and methods: </strong>Blood samples were withdrawn from 50 BD patients and 40 age and sex-matched healthy individuals in this study.</p><p><strong>Results: </strong>Serum expression levels of miR-34a and miR-182 were significantly elevated in BD patients when compared to controls, <i>p</i> < .001. However, serum expression levels of miR-378 were significantly decreased in BD patients compared to controls, <i>p</i> < .001. miR-182 serum levels were also found to be elevated in active BD patients compared to patients in inactive state (<i>p</i> = .022). We found a significant association between miR-34 levels and joint affection in BD patients as well as a significant relation between miR-182 levels and each of neurological manifestations and genital ulcerations. In addition, a statistically significant positive correlations were proved in the current results between miR-182 expression and BDCAF score (<i>r</i> = 0.419, <i>p</i> = .002) as well as severity score (<i>r</i> = 0.358, <i>p</i> = .011).</p><p><strong>Conclusion: </strong>Our study denoted that the three miRNAs; miR-34a, miR-182, and miR-378 possibly play a crucial role in the pathogenesis of BD. The distinction of their serum levels between patients and healthy individuals suggested their potentiality as promising biomarkers for BD.</p>","PeriodicalId":8331,"journal":{"name":"Archives of Physiology and Biochemistry","volume":" ","pages":"1-10"},"PeriodicalIF":2.5,"publicationDate":"2025-04-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143962641","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Protective role of butylated hydroxyanisole (BHA) and hydroxytoluene (BHT) against oxidative stress-induced inflammatory response in carbon tetrachloride-induced acute hepatorenal toxicity.","authors":"Barsha Dassarma, Santanu Kar Mahapatra, Dilip Kumar Nandi, Somnath Gangopadhyay, Saptadip Samanta","doi":"10.1080/13813455.2025.2493105","DOIUrl":"https://doi.org/10.1080/13813455.2025.2493105","url":null,"abstract":"<p><strong>Background: </strong>Any toxicity initially damages the hepatic system, followed by renal dysfunction. Previously, it was established that carbon tetrachloride (CCl<sub>4</sub>) intoxication severely damaged hepatocytes. Moreover, CCl<sub>4</sub>-mediated toxicity significantly impacted immune functions and influenced the inflammatory response, with mitochondrial dysfunction. The present study focused on the levels of inflammatory markers and mitochondrial dysfunction, as well as the protective role of BHA and BHT.</p><p><strong>Methods: </strong>In the present study, hepatorenal dysfunction was developed in experimental rats by applying a subcutaneous injection of CCl<sub>4</sub> with a dose of 230 mg/kg bwt/rat/day. The level of immune toxicity was determined by measuring C-reactive protein (CRP), IL-6, 12, TNF-α, IL-10, and TGF-β in CCl4 intoxicated group and pretreated BHA and BHT groups. ROS generation and MMP were also measured in hepatic and renal cells using flow cytometric technique.</p><p><strong>Results: </strong>The level of toxicity was determined by a significant increase of CRP (407.29%), IL-6 (525.65%), IL-12 (1026.54%), and TNF-α (1007.33%) in CCl<sub>4</sub> intoxicated group, while IL-10 and TGF-β were significantly decreased 84.65% and 66.36%, respectively. CCl<sub>4</sub> intoxication caused decreased mitochondrial membrane potential and high levels of intracellular ROS generation. Pretreatment with BHA (0.5 mg/kg/bwt) and BHT (0.8 mg/kg/bwt) significantly (<i>p</i><0.001, <i>p</i><0.05) reduced inflammatory markers in the CCl4-treated group, restored mitochondrial membrane potential and decreased intracellular ROS levels.</p><p><strong>Conclusion: </strong>BHA and BHT treatment could restrict the higher concentration of pro-inflammatory markers by scavenging ROS. Therefore, the study suggested that supplementation of BHA and BHT could be an alternative treatment for preventing hepatorenal dysfunctions.</p>","PeriodicalId":8331,"journal":{"name":"Archives of Physiology and Biochemistry","volume":" ","pages":"1-8"},"PeriodicalIF":2.5,"publicationDate":"2025-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143959890","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}