Antioxidant effects of a novel pioglitazone analogue (PA9) in a rat model of diabetes: Modulation of redox homeostasis and preservation of tissue architecture

IF 2.9 3区医学 Q3 ENDOCRINOLOGY & METABOLISM Journal of diabetes and its complications Pub Date : 2024-10-22 DOI:10.1016/j.jdiacomp.2024.108897

Neda Shakour , Mohammad Reza Mahdinezhad , Fereshteh Asgharzadeh , Majid Khazaei , Luis E. Simental-Mendía , Nema Mohamadian Roshan , Amirhossein Sahebkar , Farzin Hadizadeh

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Abstract

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.

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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

无氧自由基与糖尿病并发症的发生有关。噻唑烷二酮类药物（TZDs）以其抗糖尿病特性而闻名，同时也具有显著的抗氧化和抗炎作用。尽管最近开发的一种吡格列酮咪唑类似物（PA9）显示出了比吡格列酮更优越的降糖疗效，但其抗氧化作用仍有待探索。因此，本研究的目的是评估 PA9 在糖尿病动物模型中的抗氧化特性。将大鼠随机分为以下四组：对照组、糖尿病组和两组，分别口服标准药物吡格列酮和 PA9 十天。实验结束后，收集大鼠的肝、心、脑、胰腺、脾和肾组织，以评估氧化/抗氧化标记物和组织学变化。与糖尿病组相比，服用 PA9 可显著降低丙二醛（MDA）水平（p < 0.05）。与糖尿病大鼠相比，接受 PA9 治疗的大鼠胰腺组织中过氧化氢酶 (CAT)、超氧化物歧化酶 (SOD) 和总硫醇这三种抗氧化标志物的水平均有所提高（p < 0.05）。此外，与糖尿病组相比，PA9 处理组心脏（p < 0.05）、脾脏（p < 0.001）、大脑和肾脏组织中的 CAT 含量明显增加，脾脏中的硫醇含量也有所增加。值得注意的是，与糖尿病大鼠相比，PA9 处理组的肝脏、胰腺、心脏、大脑、脾脏和肾脏均未观察到明显的组织学变化。PA9 能有效减轻氧化应激，调节氧化还原平衡，有望预防糖尿病并发症。这种类似物经证实的安全性突出了它的潜力，值得进行全面的临床评估，以彻底了解它在糖尿病治疗中的治疗范围和疗效。

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来源期刊

Journal of diabetes and its complications 医学-内分泌学与代谢

CiteScore

5.90

自引率

3.30%

发文量

153

审稿时长

16 days

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.