Naunyn-schmiedebergs Archives of Pharmacology最新文献

{"title":"A novel nanoformulation of parthenolide coated with polydopamine shows selective cytotoxicity and induces apoptosis in gastric cancer cells","authors":"Parisa Karimian Ensaf, Mohammad Taghi Goodarzi, Masoud Homayouni Tabrizi, Ali Neamati, Samira Sadat Hosseinyzadeh","doi":"10.1007/s00210-023-02907-6","DOIUrl":"https://doi.org/10.1007/s00210-023-02907-6","url":null,"abstract":"<p>An anticancer agent derived from a natural product, parthenolide (PN), was studied to formulate PN into poly(lactic-co-glycolic acid) (PLGA). Polydopamine (PDA) was employed to modify the surface of PN-PLGA. Following characterization, the PN-PLGA-PDA was evaluated for its in vitro release, cytotoxicity, and ability to induce apoptosis using flow cytometry and real-time quantitative PCR. According to the present study, PN-PLGA-PDA had a size of 195.5 nm which is acceptable for efficient enhanced permeation and retention (EPR) performance. The SEM results confirmed the size and spherical shape of the nanoparticles. The percentage of encapsulation efficiency was 96.9%. The zeta potential of PN-PLGA-PDA was − 31.8 mV which was suitable for its stability. FTIR spectra of the PN-PLGA-PDA indicated the chemical stability of the PN due to intermolecular hydrogen bonds between polymer and drug. The release of PN from PN-PLGA-PDA in PBS (pH 7.4) was only 20% during the first 48 h and less than 40% during 144 h. PN-PLGA-PDA exhibited anticancer properties in a dose-dependent manner that was more cytotoxic against cancer cells than normal cells. Moreover, real-time qPCR results indicated that the formulation activated apoptosis genes to exert its cytotoxic effect and activate the NF-kB pathway. Based on our findings, PN-PLGA-PDA could serve as a potential treatment for cancer.</p>","PeriodicalId":18862,"journal":{"name":"Naunyn-schmiedebergs Archives of Pharmacology","volume":"29 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138716090","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}

{"title":"New phosphodiesterase-4 inhibitors present airways relaxant activity in a guinea pig acute asthma model","authors":"","doi":"10.1007/s00210-023-02905-8","DOIUrl":"https://doi.org/10.1007/s00210-023-02905-8","url":null,"abstract":"<h3>Abstract</h3> <p>Asthma is a disease characterized by chronic inflammation and hyper responsiveness of airways. We aimed to assess the relaxant potential of phosphodiesterase-4 (PDE4) inhibitors N-sulfonilhidrazonic derivatives on non-asthmatic and asthmatic guinea pig trachea. Firstly, guinea pigs were sensitized and challenged with ovalbumin, and then morphological, and contractile changes were evaluated resulting from asthma, followed by evaluation of relaxant effect of derivatives on guinea pig trachea and the cAMP levels measurement by ELISA. It has been evidenced hypertrophy of airway smooth muscle, inflammatory infiltrate, and vascular abnormalities. Moreover, only sensitized tracheal rings were responsive to OVA. Contractile response to histamine, but not to carbachol, was greater in sensitized animals, however the relaxant response to aminophylline and isoprenaline were the same in non-asthmatics and asthmatics. N-sulfonilhidrazonic derivatives presented equipotent relaxant action independent of epithelium, with exception of LASSBio-1850 that presented a low efficacy (&lt; 50%) and LASSBio-1847 with a 4-fold higher potency on asthmatics. LASSBio-1847 relaxant curve was impaired in the presence of propranolol and potentiated by isoprenaline in both groups. Furthermore, relaxation was potentiated 54- and 4-fold by forskolin in non-asthmatics and asthmatics, respectively. Likewise, LASSBio-1847 potentiated relaxant curve of aminophylline 147- and 4-fold in both groups. The PKA inhibitor H-89 impaired the relaxant potency of the derivative. Finally, LASSBio-1847 increased tracheal intracellular cAMP levels similarly to rolipram, selective PDE4 inhibitor, in both animals. LASSBio-1847 showed to be promising to relax guinea pig trachea from non-sensitized and sensitized guinea pigs by activation of β₂-adrenergic receptors/AC/cAMP pathway.</p>","PeriodicalId":18862,"journal":{"name":"Naunyn-schmiedebergs Archives of Pharmacology","volume":"9 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138716549","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}

{"title":"Population pharmacokinetic modeling of levodropropizine: extended application to comparative analysis between commercial formulations and exploration of pharmacokinetic effects of diet","authors":"Seung-Hyun Jeong, Ji-Hun Jang, Yong-Bok Lee","doi":"10.1007/s00210-023-02889-5","DOIUrl":"https://doi.org/10.1007/s00210-023-02889-5","url":null,"abstract":"<p>Levodropropizine, a nonopioid antitussive agent, is being increasingly used in clinical practice with the development of several formulations for symptomatic relief of acute and chronic bronchitis. However, scientific and quantitative population pharmacokinetic analyses of levodropropizine are lacking. Moreover, no integrated quantitative comparison has been performed between formulations. This study quantitatively evaluated and predicted pharmacokinetic properties of formulations through population pharmacokinetic model–based comparisons of commercially available formulations. Plasma concentration profile results from bioequivalence studies of 60-mg immediate release (IR) levodropropizine tablets in 40 healthy Korean males were used as population pharmacokinetic modeling data. For interindividual variability in levodropropizine pharmacokinetics, body surface area was identified as an effective covariate that was positively correlated with peripheral compartment distribution volume. Population pharmacokinetic model for IR tablets well-described the levodropropizine syrup and capsule datasets, suggesting no significant differences in pharmacokinetics among IR tablets, syrups, and capsules of levodropropizine. In contrast, pharmacokinetic profiles differed between 90-mg controlled release (CR) and IR levodropropizine tablets; however, separate parameter estimation was possible by applying the same model structure. In terms of pharmacokinetics, twice-daily regimen of 90-mg CR tablets was equivalent to thrice-daily regimen of 60-mg IR tablets. However, at steady-state, interindividual plasma concentration variability within population was reduced by approximately 36.71–83.18%. For levodropropizine CR tablets, a high-fat diet significantly delayed gastrointestinal absorption but maintained overall plasma exposure equivalent. This study provides useful quantitative judgment data for precision medicine of levodropropizine and can be helpful in predicting the pharmacokinetics of levodropropizine based on commercialized formulation switching.</p>","PeriodicalId":18862,"journal":{"name":"Naunyn-schmiedebergs Archives of Pharmacology","volume":"18 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-12-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138682313","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}

{"title":"The protective role of l-carnitine on oxidative stress, neurotransmitter perturbations, astrogliosis, and apoptosis induced by thiamethoxam in the brains of male rats","authors":"Heba-Tallah Abd Elrahim Abd Elkader, Marium Marzoq Hussein, Nema A . Mohammed, Heba M . Abdou","doi":"10.1007/s00210-023-02887-7","DOIUrl":"https://doi.org/10.1007/s00210-023-02887-7","url":null,"abstract":"<p>Synthetic organic insecticides such as pyrethroids, organophosphates, neonicotinoids, and others have the potential to disrupt ecosystems and are often toxic to humans. Thiamethoxam (TMX), a neonicotinoid insecticide , is a widely used insecticide with neurotoxic potential. <span>l</span>-Carnitine (LC) is regarded as the “gatekeeper” in charge of allowing long-chain fatty acids into cell mitochondria. LC is an endogenous chemical that is renowned for its prospective biological activity in addition to its role in energy metabolism. This study investigated the protective effects of LC against TMX-induced neurotoxicity in male Wistar rats. For 28 days, animals were divided into four groups and treated daily with either LC (300 mg/kg), TMX (100 mg/kg), or both at the aforementioned doses. Our results revealed marked serum lipid profile and electrolyte changes, declines in brain antioxidants and neurotransmitters (acetylcholine, dopamine, and serotonin levels) with elevations in thiobarbituric acid reactive substances and proinflammatory cytokine levels, as well as acetylcholinesterase and monoamine oxidase brain activity in TMX-treated rats. TMX also increased the expression of caspase-3 and glial fibrillary acidic protein. In contrast, pretreatment with LC attenuated TMX-induced brain injury by suppressing oxidative stress and proinflammatory cytokines and modulating neurotransmitter levels. It also ameliorated the expression of apoptotic and astrogliosis markers. It could be concluded that LC has antioxidant, anti-inflammatory, anti-astrogliosis, and anti-apoptotic potential against TMX neurotoxicity.</p><h3 data-test=\"abstract-sub-heading\">Graphical abstract</h3>\u0000","PeriodicalId":18862,"journal":{"name":"Naunyn-schmiedebergs Archives of Pharmacology","volume":"9 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-12-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138686850","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}

{"title":"The evaluation of atorvastatin as an adjunct to fluconazole for the anti-fungal prophylaxis in acute myeloid leukemia: a multicenter, triple-blinded, randomized clinical trial","authors":"Niloufar Saber-Moghaddam, Mohammad Moeini Nodeh, Vahid Ghavami, Hossein Rahimi, Sajjad Ataei Azimi, Mohsen Seddigh-Shamsi, Mostafa Kamandi, Abolghasem Allahyari, Somayeh Sadat Shariatmaghani, Sepideh Elyasi, Omid Arasteh","doi":"10.1007/s00210-023-02892-w","DOIUrl":"https://doi.org/10.1007/s00210-023-02892-w","url":null,"abstract":"<p>The development of invasive fungal infections (IFIs) is a serious complication in acute myeloid leukemia (AML) patients who undergo an induction to remission chemotherapy. Given the increased mortality in AML patients with IFI despite prophylaxis, we need to address this problem. Statins have traditionally been employed in clinical settings as agents for reducing lipid levels. Nonetheless, recent investigations have brought to light their antifungal properties in animals, as well as in vitro studies. The objective of this study was to assess the effectiveness of atorvastatin when added to the routine IFI prophylaxis regimen in patients diagnosed with AML. A randomized, multicenter, triple-blind study was conducted on 76 AML patients aged 18–70, who received either placebo or atorvastatin in addition to fluconazole. Patients were followed for 30 days in case of developing IFIs, patient survival, and atorvastatin- related adverse drug reactions. Data were analyzed with SPSS version 26.0. A level of significance of 0.05 was utilized as the threshold for all statistical tests. The data were analyzed by adjusting for the effect of age, regarding that there was a significant difference between the two groups, and showed that atorvastatin reduced the development of both probable and proven IFI (based on EORTC/MSGERC criteria) compared to placebo. IFI-free survival was also significantly better in the atorvastatin group. The incidence of developing aspergillosis did not differ between the two groups. No serious adverse events related to atorvastatin were observed. The present investigation has substantiated the antecedent in vitro and animal research on the fungicidal impact of statins and has suggested the need for additional research involving larger sample sizes and an extended duration of follow-up. Trial registration: This study was registered on the Iranian registry of clinical trials as IRCT20210503051166N1 (Date of confirmation 2021.05.03).</p>","PeriodicalId":18862,"journal":{"name":"Naunyn-schmiedebergs Archives of Pharmacology","volume":"98 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-12-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138629049","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}

{"title":"Comparison of bolus administration and short-term infusion versus long-term infusion of doxorubicin in terms of cardiotoxicity and efficacy","authors":"Hamed Ghiami, Navid Omidkhoda, Mohsen Seddigh-Shamsi, Hossein Rahimi, Omid Arasteh","doi":"10.1007/s00210-023-02886-8","DOIUrl":"https://doi.org/10.1007/s00210-023-02886-8","url":null,"abstract":"<p>Cardiotoxicity caused by anthracyclines chemotherapy is one of the leading causes of mortality and morbidity in cancer survivors. Continuous infusion (CI) instead of bolus (BOL) injection is one of the methods that seem to be effective in reducing doxorubicin (DOX) cardiotoxicity. Due to the variety of results, we decided to compare these two approaches regarding toxicity and efficacy and report the final results for different cancers. We included 21 studies (four preclinical and seventeen clinical trials) up to May 15, 2023. In children with acute lymphoblastic leukemia (ALL) and adults with chronic lymphoblastic leukemia (CLL) and gastric cancer, results were in favor of BOL injection, without increase in cardiotoxicity. On the other hand, CI showed to be better option in patients with small-cell lung cancer (SCLC) and breast cancer. Various results were also observed in adult patients with sarcoma. Overall, it can be concluded that the benefits of CI, especially in adults, outweigh its disadvantages. However, due to the variety of results and heterogeneity of studies, further clinical trials with a larger sample size and a longer duration of follow-up are needed to make a more accurate comparison between CI and BOL injection.</p>","PeriodicalId":18862,"journal":{"name":"Naunyn-schmiedebergs Archives of Pharmacology","volume":"40 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-12-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138629052","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}

{"title":"Unveiling innovative therapeutic strategies and future trajectories on stimuli-responsive drug delivery systems for targeted treatment of breast carcinoma","authors":"Israa Habeeb Naser, Muhaned Zaid, Eyhab Ali, Hayder Imad Jabar, Anfal Nabeel Mustafa, Mahmood Hasen Shuhata Alubiady, Montather F. Ramadan, Khursheed Muzammil, Reem Mohsin Khalaf, Sarah Salah Jalal, Ahmed Hussien Alawadi, Ali Alsalamy","doi":"10.1007/s00210-023-02885-9","DOIUrl":"https://doi.org/10.1007/s00210-023-02885-9","url":null,"abstract":"<p>This comprehensive review delineates the latest advancements in stimuli-responsive drug delivery systems engineered for the targeted treatment of breast carcinoma. The manuscript commences by introducing mammary carcinoma and the current therapeutic methodologies, underscoring the urgency for innovative therapeutic strategies. Subsequently, it elucidates the logic behind the employment of stimuli-responsive drug delivery systems, which promise targeted drug administration and the minimization of adverse reactions. The review proffers an in-depth analysis of diverse types of stimuli-responsive systems, including thermoresponsive, pH-responsive, and enzyme-responsive nanocarriers. The paramount importance of material choice, biocompatibility, and drug loading strategies in the design of these systems is accentuated. The review explores characterization methodologies for stimuli-responsive nanocarriers and probes preclinical evaluations of their efficacy, toxicity, pharmacokinetics, and biodistribution in mammary carcinoma models. Clinical applications of stimuli-responsive systems, ongoing clinical trials, the potential of combination therapies, and the utility of multifunctional nanocarriers for the co-delivery of assorted drugs and therapies are also discussed. The manuscript addresses the persistent challenge of drug resistance in mammary carcinoma and the potential of stimuli-responsive systems in surmounting it. Regulatory and safety considerations, including FDA guidelines and biocompatibility assessments, are outlined. The review concludes by spotlighting future trajectories and emergent technologies in stimuli-responsive drug delivery, focusing on pioneering approaches, advancements in nanotechnology, and personalized medicine considerations. This review aims to serve as a valuable compendium for researchers and clinicians interested in the development of efficacious and safe stimuli-responsive drug delivery systems for the treatment of breast carcinoma.</p>","PeriodicalId":18862,"journal":{"name":"Naunyn-schmiedebergs Archives of Pharmacology","volume":"22 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-12-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138629402","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}

{"title":"Cytoprotective potency of naringin against di-n-butylphthalate (DBP)-induced oxidative testicular damage in male rats","authors":"Anis Anis, Sameh H. El-Nady, Hany A. Amer, Hamed T. Elbaz, Ahmed E. Elweza, Nermeen Borai El-Borai, Salah S. El-Ballal","doi":"10.1007/s00210-023-02874-y","DOIUrl":"https://doi.org/10.1007/s00210-023-02874-y","url":null,"abstract":"<p>The present study aimed to investigate the protective potential of naringin (NG) against di-n-butyl phthalate (DBP)- induced testicular damage and impairment of spermatogenesis in rats. Forty-two male Wistar albino rats were divided into six equal groups, and treated orally, 3 times weekly for 8 successive weeks. Control vehicle group was administrated olive oil, naringin-treated group was administered NG (80 mg/kg), DBP 250- and DBP 500- intoxicated groups received DBP (250 mg/kg) and (500 mg/kg), respectively, NG + DBP 250 and NG + DBP 500 groups received NG, an hour prior to DBP 250 and 500 administration. The results revealed that DBP induced dose-dependent male reproductive dysfunctions, included a significant decrease in the serum testosterone level concomitantly with significant decreases in the sperm count, viability, and total motility. Meanwhile, DBP significantly increased the testicular malondialdehyde level with significant reductions of glutathione content and catalase activity. Histopathologically, DBP provoked absence of spermatozoa, degenerative changes in the cell layers of seminiferous tubules and a significant decrease in the thickness of the seminiferous tubules epithelium. Conversely, the concomitant treatment with NG, one hour before DBP 250 or 500- intoxication mitigated the dose-dependent reproductive dysfunctions induced by DBP, evidenced by significant increases of serum testosterone level, sperm motility, count and viability along with marked improvement of the oxidant/antioxidant status and testicular histoarchitecture. In conclusion, the findings recorded herein proved that NG could mitigate DBP-induced testicular damage and impairment of spermatogenesis, suggesting the perspective of using NG as a natural protective and therapeutic agent for alleviating the reproductive dysfunctions and improving reproductive performance, mainly via its potent antioxidant activity.</p>","PeriodicalId":18862,"journal":{"name":"Naunyn-schmiedebergs Archives of Pharmacology","volume":"101 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-12-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138629836","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}

{"title":"Niosomes loading N-acetyl-L-cysteine for cancer treatment in vivo study","authors":"Ebtesam A. Mohamad, Abeer A. Ali, Marwa Sharaky, Reem H. El-Gebaly","doi":"10.1007/s00210-023-02893-9","DOIUrl":"https://doi.org/10.1007/s00210-023-02893-9","url":null,"abstract":"<p>Scientists are seeking to find an effective treatment for tumors that has no side effects. N-Acetyl-l-cysteine (NAC) is a thiol compound extracted from garlic. Current study explores the potential of NAC-loaded niosomes (NAC-NIO) for tumor treatment in mice. NAC-loaded niosomes’ efficiency, morphology, UV absorption, size distribution, zeta potential, release, and FTIR analysis were evaluated. For vivo study, 25 male BALB/c mice were divided to five groups: gp1 negative control (receive saline), gp2 positive control (tumor group), gp3 treated with NAC, gp4 treated with NAC-NIO at the same time of tumor injection, and gp5 treated with NAC-NIO after tumor growth (day 14). The impact of NAC-NIO on the tumor treatment was evaluated by measuring tumor size progress, comet assay, oxidative stress parameters (GSH, nitric oxide, MDA), western blot analysis, and histopathological investigation of tissues. NAC-NIO showed 72 ± 3% encapsulation efficiency and zeta potential − 5.95 mV with spherical shape. It was found that oral administration of NAC-NIO in a dose of 50 mg/kg provided significant protection against tumor cells. Our formulation decreases DNA injury significantly (<i>P</i> &lt; 0.05). It was noticed that NAC-NIO can increase oxidative stress levels in tumor tissue. On the other hand, the caspase 3 and caspase 9 gene expression were upregulated significantly (<i>P</i> &lt; 0.001) in mice administrated NAC-NIO compared with all other groups. Histological studies confirmed the protective effect of NAC-NIO against tumor especially for treatment during tumor growth protocol. The results suggested that oral delivery of NAC-NIO formulation improved antioxidant effect.</p>","PeriodicalId":18862,"journal":{"name":"Naunyn-schmiedebergs Archives of Pharmacology","volume":"16 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-12-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138629040","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}

{"title":"Study on the mechanism of vitamin E alleviating non-alcoholic fatty liver function based on non-targeted metabolomics analysis in rats","authors":"Baiyun Zhao, Jing Zhang, Kaiyue Zhao, Wenbin Zhao, Yajuan Shi, Jing Liu, Ling Zeng, Chaoxuan Wang, Xin Zeng, Junping Shi","doi":"10.1007/s00210-023-02864-0","DOIUrl":"https://doi.org/10.1007/s00210-023-02864-0","url":null,"abstract":"<p>Non-alcoholic fatty liver disease (NAFLD) is a hepatic manifestation of metabolic syndrome. Vitamin E (VE) has antioxidant properties and can mediate lipid metabolism. Non-targeted metabolomics technology was employed to uncover comprehensively the metabolome of VE in NAFLD rats. NAFLD model was created with a high-fat and high-cholesterol diet (HFD) in rats. NAFLD rats in the VE group were given 75 mg/(kg day) VE. The metabolites in the serum of rats were identified via UPLC and Q-TOF/MS analysis. KEGG was applied for the pathway enrichment. VE improved the liver function, lipid metabolism, and oxidative stress in NAFLD rats induced by HFD. Based on the metabolite profile data, 132 differential metabolites were identified between VE group and the HFD group, mainly including pyridoxamine, betaine, and bretylium. According to the KEGG results, biosynthesis of cofactors was a key metabolic pathway of VE in NAFLD rats. VE can alleviate NAFLD induced by HFD, and the underlying mechanism is associated with the biosynthesis of cofactors, mainly including pyridoxine and betaine.</p>","PeriodicalId":18862,"journal":{"name":"Naunyn-schmiedebergs Archives of Pharmacology","volume":"68 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-12-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138629053","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}