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

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.

Telmisartan inhibits the non-canonical TGF-β/JAK2/STAT3 signaling pathway and prevents carbon tetrachloride-induced liver fibrosis in rats

“…The consistent oxidative liver damage caused by CCl4 intoxication induces inflammation that ultimately causes fibrosis of the liver 34 . In accordance with previous reports, accumulating oxidative stress by CCl4 in this study excites a clear inflammatory reaction with inflammatory cells infiltration as well as elevation in inflammatory cytokine level (IL-6) in liver tissue 17,26 . Meanwhile, telmisartan treatment significantly lowered hepatic IL-6 level and inflammatory cell infiltration in liver tissue of CCl4 intoxicated rats.…”

“…Our data is in line with the evident antioxidant activity seen in telmisartan treated group. These data are also in accordance with other reports in which telmisartan has been shown to significantly reduce lipid peroxidation, inflammatory cytokine secretion and expression, henceforth reduces the progression of tissue injury 26,28,35,36 . Telmisartan has been also documented to significantly reduce inflammatory cell infiltration in liver tissue 26,37 .…”

“…These data are in accordance with the increase in serum hepatic injury markers (ALT and AST) that can be explained by the elevated oxidative stress and the consequent lipid peroxidation and liver injury that may alter transport and permeability function of cellular membrane in injured hepatic cells, resulting in outflow of the enzymes from hepatic cells into the blood flow 25 . Conversely telmisartan treatment showed antioxidant and hepatoprotective effects as evidenced from the elevated TAC, decreased liver index, MDA, and serum liver injury markers in CCl4 intoxicated animals 26,28 . The hepatoprotective effects of telmisartan may be in part based on drug's antioxidative action 29,30 .…”

Olmesartan medoxomil self-microemulsifying drug delivery system reverses apoptosis and improves cell adhesion in trinitrobenzene sulfonic acid-induced colitis in rats

“…OM was prepared in a SNEDDS formula composed of oil part (oleic acid 10% w/w), surfactant mixture (tween 80 and span 85, 1:1 weight ratio 50% w/w), and cosurfactant (labrasol 40% w/w). The OMS formula was prepared as early as reported (Murad et al., 2020 ). The concentration of OM in SNEDDS components was 10 mg/g formula.…”

“…The concentrations of the olmesartan in plasma and the colonic homogenate were measured by HPLC/MS (Sharma & Pancholi, 2010 ). The sample extraction and analysis were done as previously reported with slight modifications (Liu et al., 2010 ; Murad et al., 2020 ).…”