Telmisartan Self-Nanoemulsifying Drug Delivery System, Compared With Standard Telmisartan, More Effectively Improves Hepatic Fibrosis in Rats

Hussam Murad; Osama Ahmed; Tawfik Ghabrah; Mamdooh Gari

doi:10.1177/1559325820982190

Telmisartan Self-Nanoemulsifying Drug Delivery System, Compared With Standard Telmisartan, More Effectively Improves Hepatic Fibrosis in Rats

Dose Response. 2020 Dec 17;18(4):1559325820982190. doi: 10.1177/1559325820982190. eCollection 2020 Oct-Dec.

Authors

Hussam Murad^{1

2}, Osama Ahmed³, Tawfik Ghabrah⁴, Mamdooh Gari⁵

Affiliations

¹ Department of Pharmacology, Faculty of Medicine, Rabigh, King Abdulaziz University, Jeddah, Saudi Arabia.
² Department of Pharmacology, Faculty of Medicine, Ain Shams University, Cairo, Egypt.
³ Department of Pharmaceutics, Faculty of Pharmacy, King Abdulaziz University, Jeddah, Saudi Arabia.
⁴ Department of Community Medicine, Faculty of Medicine, King Abdulaziz University, Jeddah, Saudi Arabia.
⁵ Department of Molecular Genetics, Faculty of Applied Medical Science, King Abdulaziz University, Jeddah, Saudi Arabia.

Abstract

Background: This study was designed to examine effects of telmisartan; an angiotensin receptor blocker; self-nanoemulsifying drug delivery system (SNEDDS) in reversing already-established hepatic fibrosis.

Method: Forty rats were given thioacetamide (200 mg/kg, intraperitoneally) twice/week for 8 weeks then divided into 5 groups (n = 8), PC and 4 treated groups. Treatments were given orally for another 2 months as follows: telmisartan low and high doses (TL and TH: 1.8 and 3.6 mg/kg/day) and telmisartan SNEDDS at the same doses (TLS and THS). At end of treatment, blood was obtained and liver was isolated.

Results: Rats showed significant elevations of plasma ALT and AST and hepatic IL-6, TNF-α, and MDA, significant reductions of plasma albumin, hepatic GSH, and body weight, and hepatic histopathological damage. All treatments except for TL significantly reversed these thioacetamide-induced changes. THS group showed significant differences from all groups. Regarding ratio of free telmisartan concentration in hepatic homogenate to that of plasma, TH and TLS groups showed non-significant variation between each other while THS group showed significant differences from them. No significant changes were detected in blood pressure, hemoglobin, white blood cells, and platelets.

Conclusion: Telmisartan SNEDDS, compared with telmisartan, more effectively reversed chronic hepatic fibrosis with good safety profile.

Keywords: liver fibrosis; telmisartan; thioacetamide.