{"title":"Δ(9)-四氢大麻酚能保护高胰岛素血症大鼠的心脏组织免受内质网和氧化应激、细胞凋亡和炎症的影响。","authors":"Zeynep Mine Coskun Yazici, Karolin Yanar, Sema Bolkent","doi":"10.1093/jpp/rgae023","DOIUrl":null,"url":null,"abstract":"<p><strong>Objectives: </strong>In our study, we aimed to examine how δ(9)-tetrahydrocannabinol (THC) administration to hyperinsulinemia (HI) model rats would change endoplasmic reticulum stress (ERS), apoptosis, inflammation, and oxidative stress in cardiac tissue.</p><p><strong>Methods: </strong>Rats were divided into four groups (n = 32): Control (C), THC, HI, and Treatment (Tre). Fructose (10%) in the drinking water was given to HI and Tre rats for 12 weeks. 1.5 mg/kg/d THC was given intraperitoneally to THC and Tre rats in the last 4 weeks of the experiment. The mRNA expressions of ERS and apoptosis markers in the cardiac tissue were detected. TNF-α concentration and oxidative stress were also analyzed.</p><p><strong>Key findings: </strong>THC treatment in rats with HI ameliorated the overexpression of GRP-78, IRE1α, ATF6, ATF4, CHOP, Cas-12, Cas-8, Cas-9, and Cas-3 mRNAs, markers of ERS and apoptosis (P < .0001 for all). In addition, THC has been shown to reduce inflammation in the Tre group by causing a decrease in increased cardiac TNF-α levels (P < .01). Moreover, THC prevented cardiac tissue damage by regulating the degraded oxidative stress marker levels and antioxidant enzyme activities in HI.</p><p><strong>Conclusions: </strong>Our findings suggest that THC treatment in rats with HI exhibited a significant effect in ameliorating cardiac tissue damage by improving the antioxidant defense system, inflammation, apoptosis, ERS, and oxidative stress.</p>","PeriodicalId":16960,"journal":{"name":"Journal of Pharmacy and Pharmacology","volume":null,"pages":null},"PeriodicalIF":2.8000,"publicationDate":"2024-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Δ(9)-tetrahydrocannabinol protects cardiac tissue against endoplasmic reticulum and oxidative stresses, apoptosis, and inflammation in rats with hyperinsulinemia.\",\"authors\":\"Zeynep Mine Coskun Yazici, Karolin Yanar, Sema Bolkent\",\"doi\":\"10.1093/jpp/rgae023\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Objectives: </strong>In our study, we aimed to examine how δ(9)-tetrahydrocannabinol (THC) administration to hyperinsulinemia (HI) model rats would change endoplasmic reticulum stress (ERS), apoptosis, inflammation, and oxidative stress in cardiac tissue.</p><p><strong>Methods: </strong>Rats were divided into four groups (n = 32): Control (C), THC, HI, and Treatment (Tre). Fructose (10%) in the drinking water was given to HI and Tre rats for 12 weeks. 1.5 mg/kg/d THC was given intraperitoneally to THC and Tre rats in the last 4 weeks of the experiment. The mRNA expressions of ERS and apoptosis markers in the cardiac tissue were detected. TNF-α concentration and oxidative stress were also analyzed.</p><p><strong>Key findings: </strong>THC treatment in rats with HI ameliorated the overexpression of GRP-78, IRE1α, ATF6, ATF4, CHOP, Cas-12, Cas-8, Cas-9, and Cas-3 mRNAs, markers of ERS and apoptosis (P < .0001 for all). In addition, THC has been shown to reduce inflammation in the Tre group by causing a decrease in increased cardiac TNF-α levels (P < .01). Moreover, THC prevented cardiac tissue damage by regulating the degraded oxidative stress marker levels and antioxidant enzyme activities in HI.</p><p><strong>Conclusions: </strong>Our findings suggest that THC treatment in rats with HI exhibited a significant effect in ameliorating cardiac tissue damage by improving the antioxidant defense system, inflammation, apoptosis, ERS, and oxidative stress.</p>\",\"PeriodicalId\":16960,\"journal\":{\"name\":\"Journal of Pharmacy and Pharmacology\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":2.8000,\"publicationDate\":\"2024-06-06\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Journal of Pharmacy and Pharmacology\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1093/jpp/rgae023\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"PHARMACOLOGY & PHARMACY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Pharmacy and Pharmacology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1093/jpp/rgae023","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"PHARMACOLOGY & PHARMACY","Score":null,"Total":0}
引用次数: 0
摘要
研究目的我们的研究旨在探讨高胰岛素血症(HI)模型大鼠服用δ(9)-四氢大麻酚(THC)会如何改变心脏组织的内质网应激(ERS)、细胞凋亡、炎症和氧化应激:大鼠分为四组(n = 32):方法:将大鼠分为四组(n = 32):对照组(C)、THC 组、HI 组和治疗组(Tre)。给 HI 和 Tre 大鼠在饮用水中添加果糖(10%),持续 12 周。在实验的最后 4 周,给 THC 和 Tre 大鼠腹腔注射 1.5 mg/kg/d THC。检测心脏组织中 ERS 和细胞凋亡标志物的 mRNA 表达。还分析了 TNF-α 浓度和氧化应激:主要研究结果:THC 治疗 HI 大鼠可改善 ERS 和细胞凋亡标志物 GRP-78、IRE1α、ATF6、ATF4、CHOP、Cas-12、Cas-8、Cas-9 和 Cas-3 mRNA 的过度表达(P < .0001)。此外,THC 还能降低心脏 TNF-α 水平,从而减轻 Tre 组的炎症反应(P < .01)。此外,THC 还通过调节 HI 中降解的氧化应激标记物水平和抗氧化酶活性来防止心脏组织损伤:我们的研究结果表明,通过改善抗氧化防御系统、炎症、细胞凋亡、ERS 和氧化应激,THC 治疗 HI 大鼠对改善心脏组织损伤有显著效果。
Δ(9)-tetrahydrocannabinol protects cardiac tissue against endoplasmic reticulum and oxidative stresses, apoptosis, and inflammation in rats with hyperinsulinemia.
Objectives: In our study, we aimed to examine how δ(9)-tetrahydrocannabinol (THC) administration to hyperinsulinemia (HI) model rats would change endoplasmic reticulum stress (ERS), apoptosis, inflammation, and oxidative stress in cardiac tissue.
Methods: Rats were divided into four groups (n = 32): Control (C), THC, HI, and Treatment (Tre). Fructose (10%) in the drinking water was given to HI and Tre rats for 12 weeks. 1.5 mg/kg/d THC was given intraperitoneally to THC and Tre rats in the last 4 weeks of the experiment. The mRNA expressions of ERS and apoptosis markers in the cardiac tissue were detected. TNF-α concentration and oxidative stress were also analyzed.
Key findings: THC treatment in rats with HI ameliorated the overexpression of GRP-78, IRE1α, ATF6, ATF4, CHOP, Cas-12, Cas-8, Cas-9, and Cas-3 mRNAs, markers of ERS and apoptosis (P < .0001 for all). In addition, THC has been shown to reduce inflammation in the Tre group by causing a decrease in increased cardiac TNF-α levels (P < .01). Moreover, THC prevented cardiac tissue damage by regulating the degraded oxidative stress marker levels and antioxidant enzyme activities in HI.
Conclusions: Our findings suggest that THC treatment in rats with HI exhibited a significant effect in ameliorating cardiac tissue damage by improving the antioxidant defense system, inflammation, apoptosis, ERS, and oxidative stress.
期刊介绍:
JPP keeps pace with new research on how drug action may be optimized by new technologies, and attention is given to understanding and improving drug interactions in the body. At the same time, the journal maintains its established and well-respected core strengths in areas such as pharmaceutics and drug delivery, experimental and clinical pharmacology, biopharmaceutics and drug disposition, and drugs from natural sources. JPP publishes at least one special issue on a topical theme each year.