Clinical and Experimental Pharmacology and Physiology最新文献_第10页

A 2-week treatment with 5-azacytidine improved the hypercontractility state in prostate from obese mice: Role of the nitric oxide-cyclic guanosine monophosphate signalling pathway 用 5-azacytidine 治疗 2 周可改善肥胖小鼠前列腺的过度收缩状态：一氧化氮-环鸟苷单磷酸信号通路的作用。

IF 2.9 4区医学

Clinical and Experimental Pharmacology and Physiology Pub Date : 2024-03-07 DOI: 10.1111/1440-1681.13851

Ana Carolina Ghezzi, Gabriela Reolon Passos, Mariana Gonçalves de Oliveira, Akila Lara Oliveira, Guilherme Rossi Assis-Mendonça, Glaucia Coelho de Mello, Edson Antunes, Fabiola Zakia Monica

{"title":"A 2-week treatment with 5-azacytidine improved the hypercontractility state in prostate from obese mice: Role of the nitric oxide-cyclic guanosine monophosphate signalling pathway","authors":"Ana Carolina Ghezzi, Gabriela Reolon Passos, Mariana Gonçalves de Oliveira, Akila Lara Oliveira, Guilherme Rossi Assis-Mendonça, Glaucia Coelho de Mello, Edson Antunes, Fabiola Zakia Monica","doi":"10.1111/1440-1681.13851","DOIUrl":"10.1111/1440-1681.13851","url":null,"abstract":"Benign prostatic hyperplasia (BPH) is characterised by increases in prostate volume and contraction. Downregulation of the nitric oxide (NO)-cyclic guanosine monophosphate (cGMP) signalling pathway contributes to prostate dysfunctions. Previous studies in cancer cells or vessels have shown that the epigenetic mechanisms control the gene and protein expression of the enzymes involved in the production of NO and cGMP. This study is aimed to evaluate the effect of a 2-week treatment of 5-azacytidine (5-AZA), a DNA-methyltransferase inhibitor, in the prostate function of mice fed with a high-fat diet. Functional, histological, biochemical and molecular assays were carried out. Obese mice presented greater prostate weight, α-actin expression and contractile response induced by the α-1adrenoceptors agonist. The relaxation induced by the NO-donor and the protein expression of endothelial nitric oxide synthase (eNOS) and soluble guanylate cyclase (sGC) were significantly decreased in the prostate of obese mice. The treatment with 5-AZA reverted the higher expression of α-actin, reduced the hypercontractility state of the prostate and increased the expression of eNOS and sGC and intraprostatic levels of cGMP. When prostates from obese mice treated with 5-AZA were incubated in vitro with inhibitors of the NOS or sGC, the inhibitory effect of 5-AZA was reverted, therefore, showing the involvement of NO and cGMP. In conclusion, our study paves the way to develop or repurpose therapies that recover the expression of eNOS and sGC and, hence, to improve prostate function in BPH.","PeriodicalId":50684,"journal":{"name":"Clinical and Experimental Pharmacology and Physiology","volume":"51 4","pages":""},"PeriodicalIF":2.9,"publicationDate":"2024-03-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140058817","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}

引用次数: 0

Study on the mechanism underlying Trichosanthis peel injection-induced improvements in myocardial fibrosis markers in patients with chronic heart failure 研究三黄皮注射液改善慢性心力衰竭患者心肌纤维化指标的机制。

IF 2.9 4区医学

Clinical and Experimental Pharmacology and Physiology Pub Date : 2024-02-29 DOI: 10.1111/1440-1681.13848

Yue He, Xinsheng Gu, Zhou Yang, Hao Wang, Ping Liu

{"title":"Study on the mechanism underlying Trichosanthis peel injection-induced improvements in myocardial fibrosis markers in patients with chronic heart failure","authors":"Yue He, Xinsheng Gu, Zhou Yang, Hao Wang, Ping Liu","doi":"10.1111/1440-1681.13848","DOIUrl":"10.1111/1440-1681.13848","url":null,"abstract":"In this research, we aimed to observe the changes in myocardial fibrosis indices in patients with chronic heart failure before and after treatment and to evaluate the anti-chronic heart failure and ventricular remodelling effects of Trichosanthis peel (TP) injection. This study was a single-center, open, single-blind, randomized controlled study with an optimal efficacy design. Patients were consecutively and randomly divided into two groups, with 36 patients in the TP injection group and 36 patients in the conventional treatment group. ELISA was used to measure changes in myocardial fibrosis indices before and after discharge, including transforming growth factor β (TGF-β), serum hyaluronic acid (HA), type I procollagen (PCI), laminin (LN) and type III procollagen (PCIII). There was no significant difference between the two groups in clinical data or baseline level of myocardial fibrosis before treatment. After treatment, compared with the conventional treatment group, the myocardial fibrosis index was significantly decreased following TP injection. Our findings indicate that TP injection combined with conventional medicine can attenuate myocardial fibrosis by reducing angiotensin II, aldosterone, TGFβ, HA, PCI, metallomatrix proteinase 2, connective tissue growth factor and LN and promote ventricular remodelling in patients with chronic heart failure.","PeriodicalId":50684,"journal":{"name":"Clinical and Experimental Pharmacology and Physiology","volume":"51 4","pages":""},"PeriodicalIF":2.9,"publicationDate":"2024-02-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139995779","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}

引用次数: 0

Phosphatidylserine accelerates wound healing and reduces necrosis in the rats: Growth factor activation 磷脂酰丝氨酸可加速大鼠伤口愈合并减少坏死：生长因子激活。

IF 2.9 4区医学

Clinical and Experimental Pharmacology and Physiology Pub Date : 2024-02-26 DOI: 10.1111/1440-1681.13849

Partow Mirzaee Saffari, Pooria Asili, Sadaf Eshraghi, Ahad Muhammadnejad, Ahmad Reza Dehpour, Ramin Goudarzi, Alireza Partoazar

{"title":"Phosphatidylserine accelerates wound healing and reduces necrosis in the rats: Growth factor activation","authors":"Partow Mirzaee Saffari, Pooria Asili, Sadaf Eshraghi, Ahad Muhammadnejad, Ahmad Reza Dehpour, Ramin Goudarzi, Alireza Partoazar","doi":"10.1111/1440-1681.13849","DOIUrl":"10.1111/1440-1681.13849","url":null,"abstract":"To examine the effect of topical phosphatidylserine (PS) on wound healing factors and tissue necrosis in in vivo models. Topical PS was applied to evaluate aspects of the wound healing process and growth factors production of vascular endothelial growth factors (VEGF) as well a necrosis reduction in the skin flap of rat models. Moreover, phenytoin (PHT) and cyclosporine A (CsA) were used topically as positive control treatments in wound and necrosis models, respectively. Immunohistochemistry (IHC) VEGF, transforming growth factor-β (TGF-β), fibroblast growth factor (FGF) and histopathology were analysed on the wounds of rats. In the necrosis assessment, necrotic areas were determined on photography taken from the back skin of rats. Results indicated that PS topically enhanced significantly (P < 0.05) numbers of fibroblasts and endothelium while inhibiting the neutrophils and macrophages during the 14 days of wound treatment. Moreover, higher values of collagen deposition and epithelialization scores as well as wound recovery percentage (near 80%) were determined significantly (P < 0.05) in the PS group compared with the control. IHC analysis determined that FGF and VEGF cytokine factors were elevated in the wound site by topical PS. Moreover, the necrotic area was significantly (P < 0.05) improved in the PS group. Our experiment indicated that wound improvement and flap survival values in PS treatments were superior to PHT and CsA control groups, respectively. In conclusion, these findings suggest the potential of PS application in the healing of wounds and control of necrosis development after surgery or skin injuries.","PeriodicalId":50684,"journal":{"name":"Clinical and Experimental Pharmacology and Physiology","volume":"51 4","pages":""},"PeriodicalIF":2.9,"publicationDate":"2024-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139971134","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}

引用次数: 0

Gaillardin exerts potent antileukemic effects on HL-60 cells and intensifies arsenic trioxide cytotoxicity: Providing new insight into sesquiterpene lactones in leukaemia treatment Gaillardin 对 HL-60 细胞具有强效抗白血病作用，并能增强三氧化二砷的细胞毒性：为倍半萜内酯治疗白血病提供新见解

IF 2.9 4区医学

Clinical and Experimental Pharmacology and Physiology Pub Date : 2024-02-21 DOI: 10.1111/1440-1681.13847

Hanieh Noormohamadi, Maryam Hamzeloo-Moghadam, Davood Bashash, Maryam Kargar, Mehrdad Izadirad, Seyedeh Zahra Hasanpour, Ahmad Gharehbaghian

{"title":"Gaillardin exerts potent antileukemic effects on HL-60 cells and intensifies arsenic trioxide cytotoxicity: Providing new insight into sesquiterpene lactones in leukaemia treatment","authors":"Hanieh Noormohamadi, Maryam Hamzeloo-Moghadam, Davood Bashash, Maryam Kargar, Mehrdad Izadirad, Seyedeh Zahra Hasanpour, Ahmad Gharehbaghian","doi":"10.1111/1440-1681.13847","DOIUrl":"https://doi.org/10.1111/1440-1681.13847","url":null,"abstract":"The use of all-trans retinoic acid and arsenic trioxide resulted in favourable therapeutic responses in standard-risk acute promyelocytic leukaemia (APL) patients. However, resistance to these agents has made treating the high-risk subgroup more problematic, and possible side effects limit their clinical dosages. Numerous studies have proven the cytotoxic properties of Gaillardin, one of the Inula oculus-christi-derived sesquiterpene lactones. Due to the adverse effects of arsenic trioxide on the high-risk subgroup of APL patients, we aimed to assess the cytotoxic effect of Gaillardin on HL-60 cells as a single or combined-form approach. The results of the trypan blue and MTT assays outlined the potent cytotoxic properties of Gaillardin. The flow cytometric analysis and the mRNA expression levels revealed that Gaillardin attenuated the proliferative capacity of HL-60 cells through cell cycle arrest and induced apoptosis via reactive oxygen species generation. Moreover, the results of synergistic experiments indicated that this sesquiterpene lactone sensitizes HL-60 cells to the cytotoxic effects of arsenic trioxide. Taken together, the findings of the present investigation highlighted the antileukemic characteristics of Gaillardin by inducing G1 cell cycle arrest and triggering apoptosis. Gaillardin acts as an antileukemic metabolite against HL-60 cells and this study provides new insight into treating APL patients, especially in the high-risk subgroup.","PeriodicalId":50684,"journal":{"name":"Clinical and Experimental Pharmacology and Physiology","volume":"51 4","pages":""},"PeriodicalIF":2.9,"publicationDate":"2024-02-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139916809","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}

引用次数: 0

Scutellarin inhibits oleic acid induced vascular smooth muscle foam cell formation via activating autophagy and inhibiting NLRP3 inflammasome activation 黄芩苷通过激活自噬和抑制 NLRP3 炎性体活化抑制油酸诱导的血管平滑肌泡沫细胞形成

IF 2.9 4区医学

Clinical and Experimental Pharmacology and Physiology Pub Date : 2024-02-21 DOI: 10.1111/1440-1681.13845

Wen-Cong Gao, Tie-Hua Yang, Bin-Bao Wang, Qian Liu, Qing Li, Xiao-Huan Zhou, Chang-Bo Zheng, Peng Chen

{"title":"Scutellarin inhibits oleic acid induced vascular smooth muscle foam cell formation via activating autophagy and inhibiting NLRP3 inflammasome activation","authors":"Wen-Cong Gao, Tie-Hua Yang, Bin-Bao Wang, Qian Liu, Qing Li, Xiao-Huan Zhou, Chang-Bo Zheng, Peng Chen","doi":"10.1111/1440-1681.13845","DOIUrl":"https://doi.org/10.1111/1440-1681.13845","url":null,"abstract":"Abnormalities in vascular smooth muscle cells (VSMCs) are pivotal in the pathogenesis of cardiovascular pathologies such as atherosclerosis and hypertension. Scutellarin (Scu), a flavonoid derived from marigold flowers, exhibits a spectrum of biological activities including anti-inflammatory, antioxidant, antitumor, immunomodulatory and antimicrobial effects. Notably, Scu has demonstrated the capacity to mitigate vascular endothelial damage and prevent atherosclerosis via its antioxidative properties. Nevertheless, the influence of Scu on the formation of VSMC-derived foam cells remains underexplored. In this study, Scu was evidenced to efficaciously attenuate oleic acid (OA)-induced lipid accumulation and the upregulation of adipose differentiation-associated protein Plin2 in a dose- and time-responsive manner. We elucidated that Scu effectively diminishes OA-provoked VSMC foam cell formation. Further, it was established that Scu pretreatment augments the protein expression of LC3B-II and the mRNA levels of Map1lc3b and Becn1, concurrently diminishing the protein levels of the NLRP3 inflammasome compared to the OA group. Activation of autophagy through rapamycin attenuated NLRP3 inflammasome protein expression, intracellular lipid droplet content and Plin2 mRNA levels. Scu also counteracted the OA-induced decrement of LC3B-II levels in the presence of bafilomycin-a1, facilitating the genesis of autophagosomes and autolysosomes. Complementarily, in vivo experiments revealed that Scu administration substantially reduced arterial wall thickness, vessel wall cross-sectional area, wall-to-lumen ratio and serum total cholesterol levels in comparison to the high-fat diet model group. Collectively, our findings suggest that Scu attenuates OA-induced VSMC foam cell formation through the induction of autophagy and the suppression of NLRP3 inflammasome activation.","PeriodicalId":50684,"journal":{"name":"Clinical and Experimental Pharmacology and Physiology","volume":"51 4","pages":""},"PeriodicalIF":2.9,"publicationDate":"2024-02-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139916808","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}

引用次数: 0

Dapagliflozin alleviates high glucose-induced injury of endothelial cells via inducing autophagy 达帕格列净通过诱导自噬减轻高血糖诱导的内皮细胞损伤

IF 2.9 4区医学

Clinical and Experimental Pharmacology and Physiology Pub Date : 2024-02-21 DOI: 10.1111/1440-1681.13846

Gen Li, Ningxin Hou, Huagang Liu, Jun Li, Hongping Deng, Hongwen Lan, Sizheng Xiong

{"title":"Dapagliflozin alleviates high glucose-induced injury of endothelial cells via inducing autophagy","authors":"Gen Li, Ningxin Hou, Huagang Liu, Jun Li, Hongping Deng, Hongwen Lan, Sizheng Xiong","doi":"10.1111/1440-1681.13846","DOIUrl":"https://doi.org/10.1111/1440-1681.13846","url":null,"abstract":"Hyperglycaemia is a key factor in the progression of diabetes complications. Dapagliflozin (DAPA), a new type of hypoglycaemic agent, has been shown to play an important role in anti-apoptotic, anti-inflammatory and antioxidant activities. Previous studies have demonstrated an endothelial protective effect of DAPA, but the underlying mechanism was still unclear. Autophagy is a homeostatic cellular mechanism that circulates unfolded proteins and damaged organelles through lysosomal dependent degradation. In this study, we aimed to investigate whether DAPA plays a protective role against high glucose (HG)-induced endothelial injury through regulating autophagy. The results showed that DAPA treatment resulted in increased cell viability. Additionally, DAPA treatment decreased interleukin (IL)-1β, IL-6, and tumour necrosis factor-α levels in endothelial cells subjected to HG conditions. We observed that HG inhibited autophagy, and DAPA increased the autophagy level by inhibiting the protein kinase B (AKT)/mammalian target of rapamycin (mTOR) signalling pathway. Chloroquine reversed all of these beneficial effects as an autophagy inhibitor. In summary, the endothelial protective effect of DAPA in HG can be attributed in part to its role in activating of autophagy via the AKT/mTOR signalling pathway. Therefore, suggesting that the activation of autophagy by DAPA may be a novel target for the treatment of HG-induced endothelial cell injury.","PeriodicalId":50684,"journal":{"name":"Clinical and Experimental Pharmacology and Physiology","volume":"51 4","pages":""},"PeriodicalIF":2.9,"publicationDate":"2024-02-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139916822","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}

引用次数: 0

Synergic actions of botulinum neurotoxin A and oxaliplatin on colorectal tumour cell death through the upregulation of TRPM2 channel-mediated oxidative stress 肉毒杆菌神经毒素 A 和奥沙利铂通过上调 TRPM2 通道介导的氧化应激对结直肠肿瘤细胞死亡产生协同作用。

IF 2.9 4区医学

Clinical and Experimental Pharmacology and Physiology Pub Date : 2024-02-13 DOI: 10.1111/1440-1681.13844

Sıdıka Demir, İpek Duman, Mustafa Nazıroğlu

{"title":"Synergic actions of botulinum neurotoxin A and oxaliplatin on colorectal tumour cell death through the upregulation of TRPM2 channel-mediated oxidative stress","authors":"Sıdıka Demir, İpek Duman, Mustafa Nazıroğlu","doi":"10.1111/1440-1681.13844","DOIUrl":"10.1111/1440-1681.13844","url":null,"abstract":"Botulinum neurotoxin A (BoNT) is being shown to have anticancer action as a potential adjuvant treatment. The transient receptor potential (TRP) melastatin 2 (TRPM2) stimulator action of BoNT was reported in glioblastoma cells, but not in colorectal cancer (HT29) cells. By activating TRPM2, we evaluated the impacts of BoNT and oxaliplatin (OXA) incubations on oxidant and apoptotic values within the HT29 cells. Control, BoNT (5 IU for 24 h), OXA (50 μM for 24 h) and their combinations were induced. We found that TRPM2 protein is upregulated and mediates enhanced BoNT and OXA-induced Ca2+ entry in cells as compared to control cells. The increase of free reactive oxygen species (ROS), but the decrease of glutathione is the main ROS responsible for TRPM2 activation on H29 exposure to oxidative stress. BoNT and OXA-mediated Ca2+ entry through TRPM2 stimulation in response to H2O2 results in mitochondrial Ca2+ overload, followed by mitochondrial membrane depolarization, apoptosis and caspase-3/-8/-9, although they were diminished in the TRPM2 antagonist groups (N-(p-amylcinnamoyl)anthranilic acid and carvacrol). In conclusion, by increasing the susceptibility of HT29 tumour cells to oxidative stress and apoptosis, the combined administration of BoNT and OXA via the targeting of TRPM2 may offer a different approach to kill the tumour cells.","PeriodicalId":50684,"journal":{"name":"Clinical and Experimental Pharmacology and Physiology","volume":"51 4","pages":""},"PeriodicalIF":2.9,"publicationDate":"2024-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139729127","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}

引用次数: 0

Chronic intermittent hypoxia-induced oxidative stress activates TRB3 and phosphorylated JNK to mediate insulin resistance and cell apoptosis in the pancreas 慢性间歇性缺氧诱导的氧化应激激活 TRB3 和磷酸化 JNK，从而介导胰腺的胰岛素抵抗和细胞凋亡

IF 2.9 4区医学

Clinical and Experimental Pharmacology and Physiology Pub Date : 2024-01-28 DOI: 10.1111/1440-1681.13843

Shan Zeng, Yeying Wang, Li Ai, Liwei Huang, Zhijuan Liu, Chunxia He, Qiaohui Bai, Yongxia Li

{"title":"Chronic intermittent hypoxia-induced oxidative stress activates TRB3 and phosphorylated JNK to mediate insulin resistance and cell apoptosis in the pancreas","authors":"Shan Zeng, Yeying Wang, Li Ai, Liwei Huang, Zhijuan Liu, Chunxia He, Qiaohui Bai, Yongxia Li","doi":"10.1111/1440-1681.13843","DOIUrl":"10.1111/1440-1681.13843","url":null,"abstract":"This study explores the potential mechanisms of obstructive sleep apnoea (OSA) complicates type 2 diabetes mellitus (T2DM) by which chronic intermittent hypoxia (CIH) induces insulin resistance and cell apoptosis in the pancreas through oxidative stress. Four- and eight-week CIH rat models were established, and Tempol (100 mg/kg/d), was used as an oxidative stress inhibitor. This study included five groups: 4-week CIH, 4-week CIH-Tempol, 8-week CIH, 8-week CIH-Tempol and normal control (NC) groups. Fasting blood glucose and insulin levels were measured in the serum. The expression levels of 8-hidroxy-2-deoxyguanosine (8-OHdG), tribbles homologue 3 (TRB3), c-Jun N-terminal kinase (JNK), phosphorylated JNK (p-JNK), insulin receptor substrate-1 (IRS-1), phosphorylated IRS-1 (Ser307) (p-IRS-1ser307), protein kinase B (AKT), phosphorylated AKT (Ser473) (p-AKTser473), B cell lymphoma protein-2 (Bcl-2), cleaved-caspase-3 (Cl-caspase-3), and the islet cell apoptosis were detected in the pancreas. CIH induced oxidative stress in the pancreas. Compared with that in the NC group and CIH-Tempol groups individually, the homeostasis model assessment of insulin resistance (HOMA-IR) and apoptosis of islet cells was increased in the CIH groups. CIH-induced oxidative stress increased the expression of p-IRS-1Ser307 and decreased the expression of p-AKTSer473. The expression levels of TRB3 and p-JNK were higher in the CIH groups than in both the CIH-Tempol and NC groups. Meanwhile, the expressions of Cl-caspase-3 and Bcl-2 were upregulated and downregulated, respectively, in the CIH groups. Hence, the present study demonstrated that CIH-induced oxidative stress might not only induce insulin resistance but also islet cell apoptosis in the pancreas through TRB3 and p-JNK.","PeriodicalId":50684,"journal":{"name":"Clinical and Experimental Pharmacology and Physiology","volume":"51 3","pages":""},"PeriodicalIF":2.9,"publicationDate":"2024-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/1440-1681.13843","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139586030","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Empagliflozin attenuates liver fibrosis in high-fat diet/streptozotocin-induced mice by modulating gut microbiota 恩格列净通过调节肠道微生物群减轻高脂饮食/链脲佐菌素诱导的小鼠肝纤维化

IF 2.9 4区医学

Clinical and Experimental Pharmacology and Physiology Pub Date : 2024-01-28 DOI: 10.1111/1440-1681.13842

Chuxin Huang, Jiali Qian, Ying Liu, Li Zhang, Yehong Yang

{"title":"Empagliflozin attenuates liver fibrosis in high-fat diet/streptozotocin-induced mice by modulating gut microbiota","authors":"Chuxin Huang, Jiali Qian, Ying Liu, Li Zhang, Yehong Yang","doi":"10.1111/1440-1681.13842","DOIUrl":"10.1111/1440-1681.13842","url":null,"abstract":"The effects of SGLT2 inhibitors on hepatic fibrosis in diabetes remain unclear. This study aimed to investigate the effects of empagliflozin on liver fibrosis in high-fat diet/streptozotocin-induced mice and the correlation with gut microbiota. After the application of empagliflozin for 6 weeks, we performed oral glucose tolerance and intraperitoneal insulin tolerance tests to assess glucose tolerance and insulin resistance, and stained liver sections to evaluate histochemical and hepatic pathological markers of liver fibrosis. Moreover, 16S rRNA amplicon sequencing was performed on stool samples to explore changes in the composition of intestinal bacteria. We finally analysed the correlation between gut microbiome and liver fibrosis scores or indicators of glucose metabolism. The results showed that empagliflozin intervention improved glucose metabolism and liver function with reduced liver fibrosis, which might be related to changes in intestinal microbiota. In addition, the abundance of intestinal probiotic Lactobacillus increased, while Ruminococcus and Adlercreutzia decreased after empagliflozin treatment, and correlation analysis showed that the changes in microbiota were positively correlated with liver fibrosis and glucose metabolism. Overall, considering the contribution of the gut microbiota in metabolism, empagliflozin might have improved the beneficial balance of intestinal bacteria composition. The present study provides evidence and indicates the involvement of the gut–liver axis by SGLT2 inhibitors in T2DM with liver fibrosis.","PeriodicalId":50684,"journal":{"name":"Clinical and Experimental Pharmacology and Physiology","volume":"51 3","pages":""},"PeriodicalIF":2.9,"publicationDate":"2024-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139586028","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}

引用次数: 0

Metabolomic modelling and neuroprotective effects of carvacrol against acrylamide toxicity in rat's brain and sciatic nerve 香芹酚对大鼠大脑和坐骨神经中丙烯酰胺毒性的代谢组学模型和神经保护作用

IF 2.9 4区医学

Clinical and Experimental Pharmacology and Physiology Pub Date : 2024-01-20 DOI: 10.1111/1440-1681.13841

Hatipoglu Durmus, Ates M. Burak, Senturk Goktug, Bulut Aysegul

{"title":"Metabolomic modelling and neuroprotective effects of carvacrol against acrylamide toxicity in rat's brain and sciatic nerve","authors":"Hatipoglu Durmus, Ates M. Burak, Senturk Goktug, Bulut Aysegul","doi":"10.1111/1440-1681.13841","DOIUrl":"https://doi.org/10.1111/1440-1681.13841","url":null,"abstract":"The study aimed to investigate the harmful effects of acrylamide (AA), which forms in carbohydrate-rich foods at temperatures above 120°C, on the central and peripheral nervous systems and to evaluate the potential neuroprotective effects of carvacrol (CRV). Male Wistar Albino rats were subjected to AA (40 mg/kg/bw/day) and CRV (50 mg/kg/bw/day) for 15 days. Following the last administration, evaluations revealed disrupted gait, heightened thermal sensitivity and altered paw withdrawal thresholds in AA-exposed rats. Notably, AA reduced glutathione (GSH) and raised malondialdehyde (MDA) levels in both brain and sciatic nerve tissues. AA raised nuclear factor erythroid 2-related factor 2 (Nrf2), caspase 3 and nuclear factor κB (NF-κB) gene expressions while decreasing NR4A2. CRV co-administration mitigated gait abnormalities, elevated GSH levels and lowered MDA levels in both tissues. CRV also modulated gene expression, reducing Nrf2 and NF-κB while increasing NR4A2. Histopathological signs of AA-induced neurodegeneration and elevated glial fibrillary acidic protein levels observed in brain and sciatic nerve tissues were rectified with simultaneous administration of CRV, thereby demonstrating neuroprotective efficacy in both regions. This study is pioneering in demonstrating CRV's neuroprotective potential against AA-induced neurotoxicity in both central and peripheral nervous systems, effectively addressing limitations in the literature. In conclusion, the study revealed AA-induced neurodegeneration in the brain and sciatic nerve, with CRV significantly mitigating this neurotoxicity. This novel research underscores CRV's promise as a neuroprotective agent against AA-induced adverse effects in both the central and peripheral nervous systems.","PeriodicalId":50684,"journal":{"name":"Clinical and Experimental Pharmacology and Physiology","volume":"51 3","pages":""},"PeriodicalIF":2.9,"publicationDate":"2024-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/1440-1681.13841","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139504616","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

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