Diuretic Potential of Fenchyl Acetate with Its Mechanism of Action: Toxicity Study.

Autor:	Bashir A; Faculty of Pharmacy, The University of Lahore, Lahore 54590, Pakistan.; Riphah Institute of Pharmaceutical Sciences, Riphah International University, Lahore 54000, Pakistan., Mushtaq MN; Faculty of Pharmacy, The University of Lahore, Lahore 54590, Pakistan., Anjum I; Department of Basic Medical Sciences, Shifa College of Pharmaceutical Sciences, Shifa Tameer-e-Millat University, Islamabad 44000, Pakistan., Younis W; Division of Endocrinology, Diabetes and Metabolism, Department of Medicine, University Grossman School of Medicine, New York, New York 10016, United States., Usman H; Department of Basic Medical Sciences, Shifa College of Pharmaceutical Sciences, Shifa Tameer-e-Millat University, Islamabad 44000, Pakistan., Anwar F; Riphah Institute of Pharmaceutical Sciences, Riphah International University, Lahore 54000, Pakistan., Dauelbait M; Department of Scientific translation, Faculty of Translation, University of Bahri, Khartoum 11111, Sudan., Bin Jardan YA; Department of Pharmaceutics, College of Pharmacy, King Saud University, P.O. Box 11451 Riyadh, Saudi Arabia., Bourhia M; Department of Chemistry and Biochemistry, Faculty of Medicine and Pharmacy, Ibn Zohr University, Laayoune 70000, Morocco.
Jazyk:	angličtina
Zdroj:	ACS omega [ACS Omega] 2023 Nov 15; Vol. 8 (47), pp. 44880-44892. Date of Electronic Publication: 2023 Nov 15 (Print Publication: 2023).
DOI:	10.1021/acsomega.3c05638
Abstrakt:	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. Competing Interests: The authors declare no competing financial interest. (© 2023 The Authors. Published by American Chemical Society.)
Databáze:	MEDLINE
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