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Diuretic Potential of Fenchyl Acetate with Its Mechanism of Action: Toxicity Study
ACS Omega ( IF 3.7 ) Pub Date : 2023-11-15 , DOI: 10.1021/acsomega.3c05638 Asifa Bashir 1, 2 , Muhammad Naveed Mushtaq 1 , Irfan Anjum 3 , Waqas Younis 4 , Halima Usman 3 , Fareeha Anwar 2 , Musaab Dauelbait 5 , Yousef A Bin Jardan 6 , Mohammed Bourhia 7
ACS Omega ( IF 3.7 ) Pub Date : 2023-11-15 , DOI: 10.1021/acsomega.3c05638 Asifa Bashir 1, 2 , Muhammad Naveed Mushtaq 1 , Irfan Anjum 3 , Waqas Younis 4 , Halima Usman 3 , Fareeha Anwar 2 , Musaab Dauelbait 5 , Yousef A Bin Jardan 6 , Mohammed Bourhia 7
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Hypertension has become a global threat and is one of the greatest risk factors for chronic kidney disease. Fenchyl acetate is a monoterpene that has been assessed for its various pharmacological activities in the past, but no study has evaluated its diuretic potential and the mechanism involved in the diuretic activity after prolonged administration in rats. Therefore, this study aimed to measure the safety and diuretic profile of fenchyl acetate in rats. For evaluating the acute toxicity, a single dose of 2000 mg/kg was administered as per the OECD guideline no. 425, and the rats were observed for 14 days. After 14 days, blood samples were assessed for biochemical, hematological, and oxidative stress parameters. For the acute diuretic study, fenchyl acetate was given in doses of 100, 200, and 400 mg/kg, and urine samples after 8 h were assessed for sodium, potassium, creatinine, uric acid excretion, and urinary output. A single dose of fenchyl acetate (F.A) was selected for prolonged diuretic activity, and furosemide was taken as the standard drug in a repeated dose administration for 7 days. Rats’ urine was assessed for pH, sodium, potassium, creatinine, and uric acid excretion along with urinary volume excretion. Furthermore, blood was withdrawn by cardiac puncture, and selected organs like the heart, liver, kidney, and spleen were analyzed for oxidative stress biomarkers. Using pharmacological antagonists or inhibitors, the involvement of L-NAME, acetylcholine, or prostaglandin in F.A.-induced diuresis was determined. Mitochondrial respiratory chain enzyme complexes were also assessed in the kidney homogenates. The acute toxicity results showed F.A to be safe as its LD50 was greater than 2000 mg/kg and there were no signs of mortality or toxicity. The acute diuretic study showed that F.A resulted in a significant and dose-dependent increase in sodium, potassium, creatinine, and uric acid excretion along with urinary output, and these results were comparable to the standard drug furosemide. Prolonged administration with F.A (400 mg/kg) resulted in a comparable excretion of sodium, potassium, creatinine, uric acid, and urine output with furosemide (15 mg/kg). The oxidative stress parameters revealed that F.A (400 mg/kg) resulted in reducing the formation of free radicals. The results from the mechanism-based studies showed the involvement of NO in inducing diuresis. Furthermore, F.A (400 mg/kg) significantly increased the mitochondrial complexes I, II, III, IV, I + III, and II + III in the kidney homogenates, thus restoring the mitochondrial enzymes and improving the renal function. The current study suggests that F.A is safe with a significant diuretic potential with the involvement of NO in its mechanism of action.
中文翻译：
乙酸芬奇酯的利尿潜力及其作用机制：毒性研究
高血压已成为全球威胁，也是慢性肾脏病的最大危险因素之一。乙酸芬奇酯是一种单萜，过去已对其各种药理活性进行了评估，但没有研究评估其利尿潜力以及在大鼠中长期给药后利尿活性的机制。因此，本研究旨在测量乙酸芬奇酯对大鼠的安全性和利尿特性。为了评估急性毒性，按照 OECD 指南第 2 号，单剂量施用 2000 mg/kg。 425，观察大鼠14天。 14 天后，对血液样本进行生化、血液学和氧化应激参数评估。对于急性利尿剂研究，给予乙酸芬奇酯的剂量为 100、200 和 400 mg/kg，并评估 8 小时后尿样的钠、钾、肌酐、尿酸排泄和尿量。选择单剂量醋酸芬奇酯(FA)以延长利尿活性，以呋塞米为标准药物，重复给药7天。评估大鼠尿液的 pH 值、钠、钾、肌酐和尿酸排泄量以及尿量排泄量。此外，通过心脏穿刺抽血，并分析心脏、肝脏、肾脏和脾脏等选定器官的氧化应激生物标志物。使用药理学拮抗剂或抑制剂，确定了 L-NAME、乙酰胆碱或前列腺素在 FA 诱导的利尿中的作用。还评估了肾匀浆中的线粒体呼吸链酶复合物。急性毒性结果表明FA是安全的，其LD50大于2000 mg/kg，并且没有死亡或毒性迹象。 急性利尿剂研究表明，FA 导致钠、钾、肌酐和尿酸排泄量以及尿量显着且呈剂量依赖性增加，这些结果与标准药物呋塞米相当。长期服用 FA (400 mg/kg) 导致钠、钾、肌酐、尿酸和尿量的排泄与呋塞米 (15 mg/kg) 相当。氧化应激参数显示，FA（400 毫克/千克）可减少自由基的形成。基于机制的研究结果表明NO参与诱导利尿。此外，FA（400 mg/kg）显着增加肾匀浆中线粒体复合物I、II、III、IV、I + III和II + III，从而恢复线粒体酶并改善肾功能。目前的研究表明，FA 是安全的，具有显着的利尿潜力，其作用机制涉及 NO。
更新日期：2023-11-15
中文翻译：
乙酸芬奇酯的利尿潜力及其作用机制：毒性研究
高血压已成为全球威胁，也是慢性肾脏病的最大危险因素之一。乙酸芬奇酯是一种单萜，过去已对其各种药理活性进行了评估，但没有研究评估其利尿潜力以及在大鼠中长期给药后利尿活性的机制。因此，本研究旨在测量乙酸芬奇酯对大鼠的安全性和利尿特性。为了评估急性毒性，按照 OECD 指南第 2 号，单剂量施用 2000 mg/kg。 425，观察大鼠14天。 14 天后，对血液样本进行生化、血液学和氧化应激参数评估。对于急性利尿剂研究，给予乙酸芬奇酯的剂量为 100、200 和 400 mg/kg，并评估 8 小时后尿样的钠、钾、肌酐、尿酸排泄和尿量。选择单剂量醋酸芬奇酯(FA)以延长利尿活性，以呋塞米为标准药物，重复给药7天。评估大鼠尿液的 pH 值、钠、钾、肌酐和尿酸排泄量以及尿量排泄量。此外，通过心脏穿刺抽血，并分析心脏、肝脏、肾脏和脾脏等选定器官的氧化应激生物标志物。使用药理学拮抗剂或抑制剂，确定了 L-NAME、乙酰胆碱或前列腺素在 FA 诱导的利尿中的作用。还评估了肾匀浆中的线粒体呼吸链酶复合物。急性毒性结果表明FA是安全的，其LD50大于2000 mg/kg，并且没有死亡或毒性迹象。 急性利尿剂研究表明，FA 导致钠、钾、肌酐和尿酸排泄量以及尿量显着且呈剂量依赖性增加，这些结果与标准药物呋塞米相当。长期服用 FA (400 mg/kg) 导致钠、钾、肌酐、尿酸和尿量的排泄与呋塞米 (15 mg/kg) 相当。氧化应激参数显示，FA（400 毫克/千克）可减少自由基的形成。基于机制的研究结果表明NO参与诱导利尿。此外，FA（400 mg/kg）显着增加肾匀浆中线粒体复合物I、II、III、IV、I + III和II + III，从而恢复线粒体酶并改善肾功能。目前的研究表明，FA 是安全的，具有显着的利尿潜力，其作用机制涉及 NO。
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