New Insights on the potential therapeutic effects of glibenclamide and Obeticholic acid against Alloxan-Induced diabetes mellitus in rat model

IF 4.8 2区医学 Q2 IMMUNOLOGY International immunopharmacology Pub Date : 2024-10-29 DOI:10.1016/j.intimp.2024.113469

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Abstract

Diabetes mellitus (DM) represents a highly prevalent metabolic disorder across the globe. This study aimed to determine the ameliorative efficacy of glibenclamide (Gli) and obeticholic acid (OCA) against biochemical and pathological changes related to alloxan-induced diabetes. Twenty male Wistar rats were allocated into four groups; Control group, Diabetic group: received intraperitoneal injection of alloxan (120 mg/kg) for induction of diabetes, Diabetic + Gli group: Diabetic rats treated daily with oral Gli (5 mg/kg) and Diabetic + OCA group: Diabetic rats treated daily with oral OCA (10 mg/kg). All rats were subjected to 30 days treatments. Our results indicated that Gli successfully ameliorated hyperglycemia and dyslipidemia with a significant decline in serum pancreatic lipase activity and increased insulin level, while OCA had the same effect but without any enhancement in serum insulin levels. Additionally, the disturbances in liver function-related parameters and the evoked oxidative stress, interleukin(IL)-6 and IL-10 in the liver and pancreas were abrogated upon treatment with Gli and OCA. Furthermore, Gli and OCA increased AMP-activated protein kinase (P-AMPK), insulin receptor substrate 1 (IRS1), farnesoid X receptor (FXR), and glucagon-like peptide-1 receptor (GLP-1R) expressions and downregulated sterol regulatory element binding protein-1c mRNA expression. Besides, Gli and OCA have alleviated diabetes-induced histopathological distortions in hepatic and pancreatic tissues and enhanced the immunoexpression of insulin, and proliferating cell nuclear antigen with decreased immune reactivity of glucagon within pancreatic tissues. Gli and OCA decreased the immune reactivity of nuclear factor kappa B and increased the glycogen content of hepatic tissues. In conclusion, OCA is efficacious in the management of dyslipidemia and hyperglycemia of DM and its related oxidative stress.

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关于格列本脲和奥贝胆酸对阿脲诱导的大鼠糖尿病模型的潜在治疗作用的新见解。

糖尿病（DM）是全球高发的代谢性疾病。本研究旨在确定格列本脲和奥贝胆酸对阿脲诱导的糖尿病相关生化和病理变化的改善作用。将 20 只雄性 Wistar 大鼠分为四组：对照组；糖尿病组：腹腔注射阿脲（120 毫克/千克）诱导糖尿病；糖尿病 + Gli 组：糖尿病 + Gli 组：糖尿病大鼠每天口服 Gli（5 毫克/千克）；糖尿病 + OCA 组：糖尿病大鼠每天口服 OCA（5 毫克/千克）：糖尿病 + OCA 组：糖尿病大鼠每天口服 OCA（10 毫克/千克）。所有大鼠均接受了 30 天的治疗。我们的研究结果表明，Gli 成功地改善了高血糖和血脂异常，显著降低了血清胰脂肪酶活性，提高了胰岛素水平，而 OCA 具有相同的效果，但没有提高血清胰岛素水平。此外，使用 Gli 和 OCA 治疗后，肝脏和胰腺中肝功能相关参数的紊乱以及诱发的氧化应激、白细胞介素（IL）-6 和 IL-10 均得到缓解。此外，Gli 和 OCA 还能增加 AMP 活化蛋白激酶（P-AMPK）、胰岛素受体底物 1（IRS1）、类胰岛素 X 受体（FXR）和胰高血糖素样肽-1 受体（GLP-1R）的表达，并下调固醇调节元件结合蛋白-1c mRNA 的表达。此外，Gli 和 OCA 还缓解了糖尿病引起的肝脏和胰腺组织病理变化，提高了胰岛素和增殖细胞核抗原的免疫表达，降低了胰高血糖素在胰腺组织中的免疫反应性。Gli 和 OCA 降低了核因子卡巴 B 的免疫反应性，增加了肝组织中的糖原含量。总之，OCA 对治疗 DM 的血脂异常和高血糖及其相关的氧化应激具有疗效。

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来源期刊

International immunopharmacology 医学-免疫学

CiteScore

8.40

自引率

3.60%

发文量

935

审稿时长

53 days

期刊介绍： International Immunopharmacology is the primary vehicle for the publication of original research papers pertinent to the overlapping areas of immunology, pharmacology, cytokine biology, immunotherapy, immunopathology and immunotoxicology. Review articles that encompass these subjects are also welcome. The subject material appropriate for submission includes: • Clinical studies employing immunotherapy of any type including the use of: bacterial and chemical agents; thymic hormones, interferon, lymphokines, etc., in transplantation and diseases such as cancer, immunodeficiency, chronic infection and allergic, inflammatory or autoimmune disorders. • Studies on the mechanisms of action of these agents for specific parameters of immune competence as well as the overall clinical state. • Pre-clinical animal studies and in vitro studies on mechanisms of action with immunopotentiators, immunomodulators, immunoadjuvants and other pharmacological agents active on cells participating in immune or allergic responses. • Pharmacological compounds, microbial products and toxicological agents that affect the lymphoid system, and their mechanisms of action. • Agents that activate genes or modify transcription and translation within the immune response. • Substances activated, generated, or released through immunologic or related pathways that are pharmacologically active. • Production, function and regulation of cytokines and their receptors. • Classical pharmacological studies on the effects of chemokines and bioactive factors released during immunological reactions.