{"title":"High-intensity interval training reduces Tau and beta-amyloid accumulation by improving lactate-dependent mitophagy in rats with type 2 diabetes.","authors":"Pouria Khosravi, Fereshte Shahidi, Arezoo Eskandari, Kayvan Khoramipour","doi":"10.22038/ijbms.2024.77038.16664","DOIUrl":"10.22038/ijbms.2024.77038.16664","url":null,"abstract":"<p><strong>Objectives: </strong>This study aimed to investigate the effect of 8-week high-intensity interval training (HIIT) on lactate-induced mitophagy in the hippocampus of rats with type 2 diabetes.</p><p><strong>Materials and methods: </strong>28 Wistar male rats were divided into four groups randomly: (i) control (Co), (ii) exercise (EX), (iii) type 2 diabetes (T2D), and (iv) type 2 diabetes + exercise (T2D + Ex). The rats in the T2D and T2D + Ex groups were fed a high-fat diet for two months, then a single dose of STZ (35 mg/kg) was injected to induce diabetes. The EX and T2D + Ex groups performed 4-10 intervals of treadmill running at 80-100% of Vmax. Serum and hippocampal levels of lactate, as well as hippocampal levels of monocarboxylate transporter2 (MCT2), sirtuin1 (SIRT1), forkhead box protein O (FOXO3), light chain 3 (LC3), PTEN-induced kinase 1 (PINK1), parkin, beta-amyloid (Aβ), hyperphosphorylated tau protein (TAU), Malondialdehyde (MDA), and antioxidant enzymes were measured. One-way ANOVA and Tukey post-hoc tests were used to analyze the data.</p><p><strong>Results: </strong>Serum and hippocampal levels of lactate as well as hippocampal levels of MCT2, SIRT1, FOXO3, LC3, PINK1, Parkin, and antioxidant enzymes were higher while hippocampal levels of Aβ, TAU, and MDA were lower in T2D+EX compared to T2D group (<i>P</i>-value<0.05).</p><p><strong>Conclusion: </strong>HIIT could improve mitophagy through Lactate-SIRT1-FOXO3-PINK1/Parkin signaling in the hippocampus of rats with T2D reducing the accumulation of Tau and Aβ, which may reduce the risk of memory impairments.</p>","PeriodicalId":14495,"journal":{"name":"Iranian Journal of Basic Medical Sciences","volume":null,"pages":null},"PeriodicalIF":2.1,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11459343/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142390529","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}
{"title":"Histopathological and biochemical evaluation of the protective efficacy of <i>Prunus spinosa</i> L. extract in a rat model of indomethacin-induced gastric ulcer.","authors":"Nihal Cetin, Esma Menevse, Cengizhan Ceylan, Zeliha Esin Celik, Neriman Akdam, Seyma Tetik Rama, Tugsen Buyukyildirim, Leyla Pasayeva, Osman Tugay, Meltem Gumus","doi":"10.22038/ijbms.2024.78382.16941","DOIUrl":"10.22038/ijbms.2024.78382.16941","url":null,"abstract":"<p><strong>Objectives: </strong>Some species of <i>Prunus</i> L. are popularly used to treat gastric ulcers. However, the possible healing mechanisms of the anti-ulcer activity of <i>P. spinosa</i>, which has proven antioxidant, anti-inflammatory, and wound-healing properties, are unclear.</p><p><strong>Materials and methods: </strong>Ethanol extracts of <i>P. spinosa</i> fruits were administered orally at 100 mg/kg and 200 mg/kg to Wistar albino rats, with an indomethacin-induced gastric ulcer model. The ulcerous areas on the stomach surface were examined macroscopically. Tissues were examined histopathologically and biochemically. LC-HRMS revealed the phytochemical content.</p><p><strong>Results: </strong>TNF-α, IL-6, IL-1β, IL-8, and NF-kB levels were higher in the gastric ulcer group than in the extract groups. The VEGF values did not differ in each group. A significant difference was found between the lansoprazole group and the high-dose <i>P. spinosa</i> group regarding PGE2 levels. A histopathologically significant difference was observed between the healthy group and the indomethacin-applied groups in terms of neutrophilic infiltration of the gastric mucosa. Ascorbic acid (1547.521 µg/g), homoprotocatechuic acid (1268.217 µg/g), and genistein (1014.462 µg/g) were found as the main compounds in the <i>P. spinosa</i> extract by LC-HRMS.</p><p><strong>Conclusion: </strong>Our results demonstrated that <i>P. spinosa</i> protected the gastric mucosa from inflammation and also modulated the PGE2 pathway. When considered in terms of TNF-α, IL-1β, IL-8, IL-6, PGE2, and NF-kB values, it can be concluded that it has a similar or even more positive effect than the reference substance. <i>P. spinosa</i> showed its effects in a dose-dependent manner.</p>","PeriodicalId":14495,"journal":{"name":"Iranian Journal of Basic Medical Sciences","volume":null,"pages":null},"PeriodicalIF":2.1,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11459347/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142390530","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}
Saeideh Saadat, Zahra Ghasemi, Arghavan Memarzia, Sepideh Behrouz, Mohammad Reza Aslani, Mohammad Hossein Boskabady
{"title":"An overview of pharmacological effects of Crocus sativous and its constituents.","authors":"Saeideh Saadat, Zahra Ghasemi, Arghavan Memarzia, Sepideh Behrouz, Mohammad Reza Aslani, Mohammad Hossein Boskabady","doi":"10.22038/IJBMS.2023.73410.15950","DOIUrl":"10.22038/IJBMS.2023.73410.15950","url":null,"abstract":"<p><p><i>Crocus sativus</i> L. was used for the treatment of a wide range of disorders in traditional medicine. Due to the extensive protective and treatment properties of <i>C. sativus</i> and its constituents in various diseases, the purpose of this review is to collect a summary of its effects, on experimental studies, both <i>in vitro</i> and <i>in vivo</i>. Databases such as PubMed, Science Direct, and Scopus were explored until January 2023 by employing suitable keywords. Several investigations have indicated that the therapeutic properties of <i>C. sativus</i> may be due to its anti-oxidant and anti-inflammatory effects on the nervous, cardiovascular, immune, and respiratory systems. Further research has shown that its petals also have anticonvulsant properties. Pharmacological studies have shown that crocetin and safranal have anti-oxidant properties and through inhibiting the release of free radicals lead to the prevention of disorders such as tumor cell proliferation, atherosclerosis, hepatotoxicity, bladder toxicity, and ethanol induced hippocampal disorders. Numerous studies have been performed on the effect of <i>C. sativus</i> and its constituents in laboratory animal models under in vitro and in vivo conditions on various disorders. This is necessary but not enough and more clinical trials are needed to investigate unknown aspects of the therapeutic properties of <i>C. sativus</i> and its main constituents in different disorders.</p>","PeriodicalId":14495,"journal":{"name":"Iranian Journal of Basic Medical Sciences","volume":null,"pages":null},"PeriodicalIF":2.2,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10897555/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139990027","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}
{"title":"Neuroprotective effects of rosemary extract on white matter of prefrontal cortex in old rats.","authors":"Mohsen Eslami Farsani, Shahnaz Razavi, Homa Rasoolijazi, Ebrahim Esfandiari, Reihaneh Seyedebrahimi, Shima Ababzadeh","doi":"10.22038/IJBMS.2023.74168.16117","DOIUrl":"10.22038/IJBMS.2023.74168.16117","url":null,"abstract":"<p><strong>Objectives: </strong>During aging, cerebral structures undergo changes due to oxidative stress. The consumption of some plants seems to improve neurological health. For example, rosemary extract (RE) which is widely used as a flavoring food has anti-inflammatory and anti-oxidant activities. Therefore, we aimed to study the effect of RE on the changes related to the aging process in the prefrontal cortex (PFC).</p><p><strong>Materials and methods: </strong>Twenty-four male Wistar rats including young and old were purchased. Each group was divided into two subgroups: vehicle and rosemary (old vehicle (OV), old rosemary (OR), young vehicle (YV), and young rosemary (YR) groups). Then, we examined the number of intact neurons, myelin base protein (MBP), white matter (WM), levels of malondialdehyde (MDA), and glutathione peroxidase (GPx) in the PFC.</p><p><strong>Results: </strong>The results showed that in the old vehicle rats compared to the young group without treatment, except for the MDA level (which increased), other variables significantly decreased (<i>P</i>≤0.05). Additionally, RE consumption demonstrated a significant elevation of WMA, MBP intensity, number of intact neurons, and GPx activity level, while MDA levels significantly reduced in the treated old rats compared to the old vehicle group (<i>P</i>≤0.05). However, there was no significant difference between the OR and YV groups (<i>P</i>≥0.05).</p><p><strong>Conclusion: </strong>Overall, it seems that RE can protect and improve aging damages in the PFC due to its anti-oxidant properties. So, the use of RE can be a suitable strategy to prevent aging complications in the brain.</p>","PeriodicalId":14495,"journal":{"name":"Iranian Journal of Basic Medical Sciences","volume":null,"pages":null},"PeriodicalIF":2.2,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10897559/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139990056","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}
{"title":"Wnt5a deficiency in osteocalcin-expressing cells could not alleviate the osteoarthritic phenotype in a mouse model of post-traumatic osteoarthritis.","authors":"Lin-Jie Feng, Xin-Hao Fan, Li-Tao Shao, Yun-Peng Zhang, Yun-Peng Hu, Yue Li, Xiao-Li Hou, Liu Zhang, Fa-Ming Tian","doi":"10.22038/IJBMS.2024.71417.15527","DOIUrl":"https://doi.org/10.22038/IJBMS.2024.71417.15527","url":null,"abstract":"<p><strong>Objectives: </strong>Wnt5a, which regulates the activities of osteoblasts and osteoclasts, is reportedly overexpressed in osteoarthritis (OA) tissues. The purpose of this study was to elucidate its role in the development of OA by deleting Wnt5a in osteocalcin (OCN)-expressing cells.</p><p><strong>Materials and methods: </strong>Knee OA was induced by anterior cruciate ligament transection (ACLT) in <i>OCN-Cre;Wnt5a</i><sup>fl/fl</sup> knockout (Wnt5a-cKO) mice and control littermates. Eight weeks after surgery, histological changes, cell apoptosis, and matrix metabolism of cartilage were evaluated by toluidine blue, TUNEL staining, and im-immunohistochemistry analyses, respectively. In addition, the subchondral bone microarchitecture of mice was examined by micro-computed tomography (micro-CT).</p><p><strong>Results: </strong>Histological scores show substantial cartilage degeneration occurred in ACLT knees, coupled with decreased collagen type II expression and enhanced matrix metalloproteinase 13 expression, as well as higher proportions of apoptotic cells. Micro-CT results show that ACLT resulted in decreased bone mineral density, bone volume/trabecular volume, trabecular number, and structure model index of subchondral bones in both Wnt5a-cKO and control littermates; although Wnt5a-cKO mice display lower BMD and BV/TV values, no significant difference was observed between Wnt5a-cKO and control mice for any of these values.</p><p><strong>Conclusion: </strong>Our findings indicate that Wnt5a deficiency in OCN-expressing cells could not prevent an osteoarthritic phenotype in a mouse model of post-traumatic OA.</p>","PeriodicalId":14495,"journal":{"name":"Iranian Journal of Basic Medical Sciences","volume":null,"pages":null},"PeriodicalIF":2.2,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11024411/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140851521","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}
Mustafa Can Güler, Ayhan Tanyeli, Ersen Eraslan, Özgür Çelebi, Demet Çelebi, Selim Çomakli, Emir Enis Yurdgülü, Yasin Bayir
{"title":"Alleviating sepsis: Revealing the protective role of costunolide in a cecal ligation and puncture rat model.","authors":"Mustafa Can Güler, Ayhan Tanyeli, Ersen Eraslan, Özgür Çelebi, Demet Çelebi, Selim Çomakli, Emir Enis Yurdgülü, Yasin Bayir","doi":"10.22038/IJBMS.2024.75372.16335","DOIUrl":"https://doi.org/10.22038/IJBMS.2024.75372.16335","url":null,"abstract":"<p><strong>Objectives: </strong>Sepsis poses a significant threat to human life, rendering it a burdensome medical disease. Despite significant advancements, the current state of medical science still lacks a viable and efficacious cure. Costunolide (COST) is a multifaceted sesquiterpene lactone that exhibits a range of actions, including anti-inflammatory and antioxidant properties. We investigated the potential impacts of COST on a rat sepsis model caused by cecal ligation and puncture (CLP).</p><p><strong>Materials and methods: </strong>We created an experimental rat model with the following groups: SHAM, CLP, CLP+low dose COST, and CLP+high dose COST. Blood, kidney, and lung samples were collected. Inflammatory mediators such as interleukin-1beta (IL-1β), IL-6, tumor necrosis factor-alpha (TNF- α), and nuclear factor kappa-B (NF-κB) were investigated. In addition, we assessed oxidative stress by measuring 8-Hydroxydeoxyguanosine (8-OHdG) immunopositivity, MDA levels, glutathione (GSH), and superoxide dismutase (SOD) activity. Histopathological and immunohistochemical examinations backed up our findings.</p><p><strong>Results: </strong>Compared to the CLP group, the COST group showed a reduction in inflammatory and oxidative stress indicators. The expression of inflammatory mediators was suppressed by COST, and histological examinations revealed improvements in kidney and lung tissues in the treatment groups.</p><p><strong>Conclusion: </strong>Our study highlights the preventive effects of COST against CLP-induced sepsis-related injury. Considering its beneficial effects against many diseases, COST is worthy as to be evaluated against sepsis.</p>","PeriodicalId":14495,"journal":{"name":"Iranian Journal of Basic Medical Sciences","volume":null,"pages":null},"PeriodicalIF":2.2,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11017843/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140858855","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}
Rasha Ezzat Mostafa, Sahar Samir Abdelrahmen, Dalia Osama Saleh
{"title":"L-Arginine-induced acute pancreatitis and its associated lung injury in rats: Down-regulation of TLR-4/MAPK-p38/JNK signaling pathway via <i>Ginkgo biloba</i> extract EGb 761.","authors":"Rasha Ezzat Mostafa, Sahar Samir Abdelrahmen, Dalia Osama Saleh","doi":"10.22038/IJBMS.2024.76162.16480","DOIUrl":"10.22038/IJBMS.2024.76162.16480","url":null,"abstract":"<p><strong>Objectives: </strong>Acute pancreatitis (AP) is an abrupt inflammatory condition characterized by a storm of inflammatory cytokines leading to high morbidity and mortality. The current study aimed to examine the efficacy of <i>Ginkgo biloba</i> extract EGb 761 (GBE) in the treatment of L-arginine-induced AP and its associated lung injury.</p><p><strong>Materials and methods: </strong>Forty rats were randomly assigned into four groups. The normal group received only saline intraperitoneally while the other groups received two intraperitoneal L-arginine injections (250 mg/100 g b.wt) separated by a 1-hour interval to provoke AP. GBE (200 and 400 mg/kg/day, PO) was administered for 2 weeks post-induction of pancreatitis. Sera and pancreatic tissues were isolated.</p><p><strong>Results: </strong>The outcome of the present study revealed that GBE ameliorated the elevated levels of serum amylase, lipase, and pancreatic inflammatory mediators viz., tumor necrosis factor-alpha (TNF-α), mitogen-activated protein kinase P38 (MAPK-P38), c-Jun N-terminal kinase 1 (JNK1), and nuclear factor-kappa B (NF-κB). Moreover, GBE restored the pancreatic gene expression of Toll-like receptor 4 (TLR4) and prostatic acid phosphatase-2 (PAP-2). Pancreatic and lung histopathological examinations confirmed the aforementioned parameters.</p><p><strong>Conclusion: </strong>GBE interfered with the mechanistic pathway of L-arginine-induced acute pancreatic and its associated lung injury. Due to its anti-inflammatory properties, GBE can be used as a novel therapeutic candidate for the treatment of AP through down-regulating TLR-4/MAPK-p38/JNK and MAPK- p38/NF-κB signaling cascades.</p>","PeriodicalId":14495,"journal":{"name":"Iranian Journal of Basic Medical Sciences","volume":null,"pages":null},"PeriodicalIF":2.1,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11193502/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141442672","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}
{"title":"Luteolin reversed anxiety and depressive-like behavior via modulation of the NF-κB/NLRP3 inflammasome axis in the hippocampus of rats subjected to sleep deprivation.","authors":"Fang Xiong, Xuewen Lv","doi":"10.22038/IJBMS.2024.75068.16277","DOIUrl":"10.22038/IJBMS.2024.75068.16277","url":null,"abstract":"<p><strong>Objectives: </strong>In this study, we assessed the impact of luteolin (LUT) on mood disorders (specifically anxiety and depression) induced by sleep deprivation (SD) by regulating pathways associated with neuroinflammation.</p><p><strong>Materials and methods: </strong>Rapid eye movement (REM) SD was employed to induce anxiety and depression in the animal subjects. The animals were treated with PAX (15 mg/kg, positive control) and LUT (10 and 20 mg/kg) for a duration of 21 days. The anxiety and depressive disorders were evaluated using behavioral tests. Following the sacrifice of the animals, hippocampal tissues were stored for molecular investigations.</p><p><strong>Results: </strong>SD resulted in anxiety, as evidenced by the elevated plus maze test and open field test. Furthermore, the findings from the sucrose performance test, forced swimming test, and tail suspension test confirmed the presence of depressive-like behaviors in the animals. The nuclear factor kappa B (NF-κB) and NLR family pyrin domain containing 3 (NLRP3) inflammasome components, including apoptosis-associated speck-like protein containing a C-terminal caspase recruitment domain (ASC), NLRP3, and active Caspase-1, were up-regulated in the hippocampus (HC) of the animals subjected to REM SD. However, treatment with LUT demonstrated a significant reversal of the behavioral changes by modulating the NF-κB and NLRP3 inflammasome components in the HC.</p><p><strong>Conclusion: </strong>It can be concluded that LUT demonstrated antidepressant effects via regulation of the NF-κB/NLRP3 inflammasome axis components in the HC.</p>","PeriodicalId":14495,"journal":{"name":"Iranian Journal of Basic Medical Sciences","volume":null,"pages":null},"PeriodicalIF":2.1,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11193505/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141442673","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}
{"title":"Acupoint catgut embedding attenuates fibromyalgia pain through attenuation of TRPV1 signaling pathway in mouse.","authors":"Feng-Chen Kao, Chia-Ming Yen, Ming-Chia Lin, Hsien-Yin Liao, Hsin-Cheng Hsu, Yi-Wen Lin","doi":"10.22038/IJBMS.2023.71431.15534","DOIUrl":"10.22038/IJBMS.2023.71431.15534","url":null,"abstract":"<p><strong>Objectives: </strong>Chronic pain is considered as pain lasting for more than three months and has emerged as a global health problem affecting individuals and society. Chronic extensive pain is the main syndrome upsetting individuals with fibromyalgia (FM), accompanied by anxiety, obesity, sleep disturbances, and depression, Transient receptor potential vanilloid 1 (TRPV1) has been reported to transduce inflammatory and pain signals to the brain.</p><p><strong>Materials and methods: </strong>Acupoint catgut embedding (ACE) is a novel acupuncture technique that provides continuous effects and convenience. ACE was performed at the bilateral ST36 acupoint.</p><p><strong>Results: </strong>We demonstrated similar pain levels among all groups at baseline. After cold stress, chronic mechanical or thermal nociception was induced (D14: mechanical: 1.85 ± 0.13 g; thermal: 4.85 ± 0.26 s) and reversed in ACE-treated mice (D14: mechanical: 3.99 ± 0.16 g; thermal: 7.42 ± 0.45 s) as well as Trpv1<sup>-/-</sup> group (Day 14, mechanical: 4.25 ± 0.2 g; thermal: 7.91 ± 0.21 s) mice. Inflammatory mediators were augmented in FM individuals and were abridged after ACE management and TRPV1 gene loss. TRPV1 and its linked mediators were increased in the thalamus (THA), somatosensory cortex (SSC), medial prefrontal cortex (mPFC), and anterior cingulate cortex (ACC) in FM mice. The up-regulation of these mediators was diminished in ACE and Trpv1<sup>-/-</sup> groups.</p><p><strong>Conclusion: </strong>We suggest that chronic pain can be modulated by ACE or Trpv1<sup>-/-</sup>. ACE-induced analgesia via TRPV1 signaling pathways may be beneficial targets for FM treatment.</p>","PeriodicalId":14495,"journal":{"name":"Iranian Journal of Basic Medical Sciences","volume":null,"pages":null},"PeriodicalIF":2.2,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10722483/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139074063","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}
Menghua Sun, Feiya Yin, Xinrong Wu, Shaoer Sun, Yongqiang An, Manlin Zhu, Xiaomin Li, Wei Liu
{"title":"Effects of ivabradine on myocardial autophagia and apoptosis in isoprenaline-induced heart failure in mice.","authors":"Menghua Sun, Feiya Yin, Xinrong Wu, Shaoer Sun, Yongqiang An, Manlin Zhu, Xiaomin Li, Wei Liu","doi":"10.22038/IJBMS.2023.70060.15236","DOIUrl":"10.22038/IJBMS.2023.70060.15236","url":null,"abstract":"<p><strong>Objectives: </strong>To investigate the effects and mechanisms of ivabradine (IVA) on isoprenaline-induced cardiac injury.</p><p><strong>Materials and methods: </strong>Forty male C57BL/6 mice were randomly divided into control group, model group, high-dose IVA group, and low-dose IVA group. The control group was given saline, other groups were given subcutaneous injections of isoproterenol (ISO) 5 mg/kg/d to make the myocardial remodeling model. A corresponding dose of IVA (high dose 50 mg/kg/d, low dose 10 mg/kg/d) was given by gavage (30 days). A transthoracic echocardiogram was obtained to detect the structure and function of the heart. An electron microscope was used to explore the cardiomyocytes' apoptosis and autophagy. HE staining and Masson's trichrome staining were performed to explore myocardial hypertrophy and fibrosis. Western blot was used to detect Bax, Bcl-2, cleaved caspase-3, Becline-1, LC3, phosphorylated p38 mitogen-activated protein kinase (p-p38MAPK), phosphorylated extracellular regulated protein kinases1/2 (p-ERK1/2), phosphorylated c-Jun N-terminal kinase (p-JNK), and α-smooth muscle actin (α-SMA) in the myocardium.</p><p><strong>Results: </strong>Heart rate in the IVA groups was reduced, and the trend of heart rate reduction was more obvious in the high-dose group. Echocardiography showed that IVA improved the cardiac structure and function compared to the model group. IVA attenuated cardiac fibrosis, decreased cardiomyocyte apoptosis, and increased autophagy. The phosphorylated MAPK in the ISO-induced groups was increased. IVA treatment decreased the p-p38MAPK level. There were no differences in p-ERK and p-JNK levels.</p><p><strong>Conclusion: </strong>The beneficial effects of IVA on myocardial injury are related to blocking the p38MAPK signal pathway, decreasing cardiomyocyte apoptosis, and increasing cardiomyocyte autophagy.</p>","PeriodicalId":14495,"journal":{"name":"Iranian Journal of Basic Medical Sciences","volume":null,"pages":null},"PeriodicalIF":2.2,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10722486/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139074068","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}