Neda Shakour , Mohammad Reza Mahdinezhad , Fereshteh Asgharzadeh , Majid Khazaei , Luis E. Simental-Mendía , Nema Mohamadian Roshan , Amirhossein Sahebkar , Farzin Hadizadeh
{"title":"新型吡格列酮类似物（PA9）在糖尿病大鼠模型中的抗氧化作用：调节氧化还原平衡和保护组织结构","authors":"Neda Shakour , Mohammad Reza Mahdinezhad , Fereshteh Asgharzadeh , Majid Khazaei , Luis E. Simental-Mendía , Nema Mohamadian Roshan , Amirhossein Sahebkar , Farzin Hadizadeh","doi":"10.1016/j.jdiacomp.2024.108897","DOIUrl":null,"url":null,"abstract":"<div><div>Oxygen-free radicals have been implicated in the initiation of diabetic complications. Thiazolidinediones (TZDs), known for their antidiabetic properties, also demonstrate notable antioxidant and anti-inflammatory effects. Although a recently developed imidazolyl analogue of pioglitazone (<strong>PA9</strong>) has exhibited superior glucose-lowering efficacy compared to pioglitazone, its antioxidant effects remain unexplored. Thus, the objective of this study is to evaluate the antioxidant properties of <strong>PA9</strong> in animal models with diabetes.</div><div>Rats were randomly separated into the following four groups: control, diabetic, and two groups treated orally with pioglitazone as a standard drug and <strong>PA9</strong> for ten days. Upon completion of the experiment, tissues from the liver, heart, brain, pancreas, spleen, and kidneys were collected to assess oxidant/antioxidant markers and histological alterations. The administration of <strong>PA9</strong> resulted in a noteworthy reduction in malondialdehyde (MDA) levels compared to the diabetic group (<em>p</em> < 0.05). The group receiving <strong>PA9</strong> displayed elevated levels of three antioxidant markers, catalase (CAT), superoxide dismutase (SOD), and total thiol, in pancreatic tissue compared to diabetic rats (<em>p</em> < 0.05).</div><div>Furthermore, increased content of CAT was evident in the heart (<em>p</em> < 0.05), spleen (<em>p</em> < 0.001), brain, and kidney tissues in the <strong>PA9</strong>-treated group, along with augmented thiol content in the spleen compared to the diabetic group. Remarkably, no significant histological changes were observed in the liver, pancreas, heart, brain, spleen, and kidneys of the <strong>PA9</strong>-treated groups relative to diabetic rats. <strong>PA9</strong> effectively mitigates oxidative stress, modulates redox homeostasis, and shows promise in preventing diabetic complications. The proven safety profile of this analogue underscores its potential, warranting comprehensive clinical evaluation to thoroughly understand its therapeutic scope and efficacy in the management of diabetes.</div></div>","PeriodicalId":15659,"journal":{"name":"Journal of diabetes and its complications","volume":"38 12","pages":"Article 108897"},"PeriodicalIF":2.9000,"publicationDate":"2024-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Antioxidant effects of a novel pioglitazone analogue (PA9) in a rat model of diabetes: Modulation of redox homeostasis and preservation of tissue architecture\",\"authors\":\"Neda Shakour , Mohammad Reza Mahdinezhad , Fereshteh Asgharzadeh , Majid Khazaei , Luis E. Simental-Mendía , Nema Mohamadian Roshan , Amirhossein Sahebkar , Farzin Hadizadeh\",\"doi\":\"10.1016/j.jdiacomp.2024.108897\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><div>Oxygen-free radicals have been implicated in the initiation of diabetic complications. Thiazolidinediones (TZDs), known for their antidiabetic properties, also demonstrate notable antioxidant and anti-inflammatory effects. Although a recently developed imidazolyl analogue of pioglitazone (<strong>PA9</strong>) has exhibited superior glucose-lowering efficacy compared to pioglitazone, its antioxidant effects remain unexplored. Thus, the objective of this study is to evaluate the antioxidant properties of <strong>PA9</strong> in animal models with diabetes.</div><div>Rats were randomly separated into the following four groups: control, diabetic, and two groups treated orally with pioglitazone as a standard drug and <strong>PA9</strong> for ten days. Upon completion of the experiment, tissues from the liver, heart, brain, pancreas, spleen, and kidneys were collected to assess oxidant/antioxidant markers and histological alterations. The administration of <strong>PA9</strong> resulted in a noteworthy reduction in malondialdehyde (MDA) levels compared to the diabetic group (<em>p</em> < 0.05). The group receiving <strong>PA9</strong> displayed elevated levels of three antioxidant markers, catalase (CAT), superoxide dismutase (SOD), and total thiol, in pancreatic tissue compared to diabetic rats (<em>p</em> < 0.05).</div><div>Furthermore, increased content of CAT was evident in the heart (<em>p</em> < 0.05), spleen (<em>p</em> < 0.001), brain, and kidney tissues in the <strong>PA9</strong>-treated group, along with augmented thiol content in the spleen compared to the diabetic group. Remarkably, no significant histological changes were observed in the liver, pancreas, heart, brain, spleen, and kidneys of the <strong>PA9</strong>-treated groups relative to diabetic rats. <strong>PA9</strong> effectively mitigates oxidative stress, modulates redox homeostasis, and shows promise in preventing diabetic complications. The proven safety profile of this analogue underscores its potential, warranting comprehensive clinical evaluation to thoroughly understand its therapeutic scope and efficacy in the management of diabetes.</div></div>\",\"PeriodicalId\":15659,\"journal\":{\"name\":\"Journal of diabetes and its complications\",\"volume\":\"38 12\",\"pages\":\"Article 108897\"},\"PeriodicalIF\":2.9000,\"publicationDate\":\"2024-10-22\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Journal of diabetes and its complications\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S105687272400223X\",\"RegionNum\":3,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q3\",\"JCRName\":\"ENDOCRINOLOGY & METABOLISM\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of diabetes and its complications","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S105687272400223X","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"ENDOCRINOLOGY & METABOLISM","Score":null,"Total":0}
Antioxidant effects of a novel pioglitazone analogue (PA9) in a rat model of diabetes: Modulation of redox homeostasis and preservation of tissue architecture
Oxygen-free radicals have been implicated in the initiation of diabetic complications. Thiazolidinediones (TZDs), known for their antidiabetic properties, also demonstrate notable antioxidant and anti-inflammatory effects. Although a recently developed imidazolyl analogue of pioglitazone (PA9) has exhibited superior glucose-lowering efficacy compared to pioglitazone, its antioxidant effects remain unexplored. Thus, the objective of this study is to evaluate the antioxidant properties of PA9 in animal models with diabetes.
Rats were randomly separated into the following four groups: control, diabetic, and two groups treated orally with pioglitazone as a standard drug and PA9 for ten days. Upon completion of the experiment, tissues from the liver, heart, brain, pancreas, spleen, and kidneys were collected to assess oxidant/antioxidant markers and histological alterations. The administration of PA9 resulted in a noteworthy reduction in malondialdehyde (MDA) levels compared to the diabetic group (p < 0.05). The group receiving PA9 displayed elevated levels of three antioxidant markers, catalase (CAT), superoxide dismutase (SOD), and total thiol, in pancreatic tissue compared to diabetic rats (p < 0.05).
Furthermore, increased content of CAT was evident in the heart (p < 0.05), spleen (p < 0.001), brain, and kidney tissues in the PA9-treated group, along with augmented thiol content in the spleen compared to the diabetic group. Remarkably, no significant histological changes were observed in the liver, pancreas, heart, brain, spleen, and kidneys of the PA9-treated groups relative to diabetic rats. PA9 effectively mitigates oxidative stress, modulates redox homeostasis, and shows promise in preventing diabetic complications. The proven safety profile of this analogue underscores its potential, warranting comprehensive clinical evaluation to thoroughly understand its therapeutic scope and efficacy in the management of diabetes.
期刊介绍：
Journal of Diabetes and Its Complications (JDC) is a journal for health care practitioners and researchers, that publishes original research about the pathogenesis, diagnosis and management of diabetes mellitus and its complications. JDC also publishes articles on physiological and molecular aspects of glucose homeostasis.
The primary purpose of JDC is to act as a source of information usable by diabetes practitioners and researchers to increase their knowledge about mechanisms of diabetes and complications development, and promote better management of people with diabetes who are at risk for those complications.
Manuscripts submitted to JDC can report any aspect of basic, translational or clinical research as well as epidemiology. Topics can range broadly from early prediabetes to late-stage complicated diabetes. Topics relevant to basic/translational reports include pancreatic islet dysfunction and insulin resistance, altered adipose tissue function in diabetes, altered neuronal control of glucose homeostasis and mechanisms of drug action. Topics relevant to diabetic complications include diabetic retinopathy, neuropathy and nephropathy; peripheral vascular disease and coronary heart disease; gastrointestinal disorders, renal failure and impotence; and hypertension and hyperlipidemia.
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