Clinical Pharmacology Department, Faculty of Medicine, Zagazig University, Zagazig, 44519, Egypt.
Department of Pharmacology, Faculty of Medicine, Mutah University, P.O. Box 7, Al-Karak, 61710, Jordan.
Naunyn Schmiedebergs Arch Pharmacol. 2024 Apr;397(4):2359-2378. doi: 10.1007/s00210-023-02771-4. Epub 2023 Oct 13.
Obesity is a key risk factor for many diseases, as cardiovascular disorders, diabetes, infertility, osteoarthritis, sleep apnea, non-alcoholic fatty liver disease (NAFLD) as well as increased risk for many cancers. Telmisartan and Candesartan cilexetil are angiotensin II receptor blockers which had proven to involve in pathogenesis of obesity and NAFLD.
This work is designed to explore the possible mitigated effects of Telmisartan and Candesartan cilexetil on weight gain and fatty liver in high fat diet (HFD) fed rats.
The HFD rat model was achieved with induction of NAFLD. For Seven weeks either telmisartan or candesartan were orally administered at doses of 5 and 10 mg/kg respectively once daily. The effects of both drugs were evaluated by measurements of rat's body weight, food intakes, length, body mass index (BMI), liver weight, inguinal and interscapular fat weights. In addition, we assayed lipid profile, liver functions tests, serum inflammatory cytokines, adipokine and leptin. Lastly, liver and adipose tissue histopathological structures were evaluated.
at end of experiment, telmisartan and candesartan were highly effective in decreasing rat's body weight from (213.1±2.68 to 191.2±2.54 and 203.5±5.89 gm , respectively), BMI, liver weight, fat weights in addition reduced serum levels of lipid and liver enzymes. Also, inflammatory cytokines were reduced with repaired histopathological insults in liver by significantly damped NAFLD score from (6.5 ±0.17 to 1±0 and 4 ±0, respectively) and decreased areas of adipocytes from (21239.12 to 5355.7 and 11607.1 um , respectively).
Telmisartan and candesartan have therapeutic potential against obesity and NAFLD induced by HFD in rats. All the previous indices showed more improvement in telmisartan than candesartan group.
肥胖是许多疾病的关键风险因素,如心血管疾病、糖尿病、不孕、骨关节炎、睡眠呼吸暂停、非酒精性脂肪性肝病(NAFLD)以及增加多种癌症的风险。替米沙坦和坎地沙坦西酯是血管紧张素 II 受体阻滞剂,已被证明与肥胖和 NAFLD 的发病机制有关。
本研究旨在探讨替米沙坦和坎地沙坦西酯对高脂饮食(HFD)喂养大鼠体重增加和脂肪肝的可能缓解作用。
通过诱导 NAFLD 建立 HFD 大鼠模型。七周内,替米沙坦或坎地沙坦分别以 5 和 10mg/kg 的剂量每天口服一次。通过测量大鼠的体重、食物摄入量、体长、体重指数(BMI)、肝重、腹股沟和肩胛间脂肪重量来评估两种药物的作用。此外,我们还测定了血脂谱、肝功能试验、血清炎症细胞因子、脂肪因子和瘦素。最后,评估了肝和脂肪组织的组织病理学结构。
实验结束时,替米沙坦和坎地沙坦可有效降低大鼠体重(分别从 213.1±2.68 降至 191.2±2.54 和 203.5±5.89g)、BMI、肝重、脂肪重量,此外还降低了血清脂质和肝酶水平。此外,炎症细胞因子也减少了,肝组织病理学损伤明显减轻,NAFLD 评分从(6.5±0.17 降至 1.0±0.0 和 4.0±0.0),脂肪细胞面积从(21239.12 降至 5355.7 和 11607.1μm)。
替米沙坦和坎地沙坦对 HFD 诱导的肥胖和 NAFLD 大鼠具有治疗潜力。所有上述指标均显示替米沙坦组比坎地沙坦组的改善更明显。