In the present study, a self nano-emulsifying drug delivery system (SNEDDS) was developed to evaluate the e ciency of TQ in hepatic ischemia/reperfusion. SNEDDS was pharmaceutically characterized to evaluate droplet size, morphology, zeta potential, thermodynamic stability, and dissolution/diffusion capacity. Animals were orally pre-treated during 10 days with TQ loaded SNEDDS. Biochemical analyses, haematoxylin-eosin staining, indirect immuno uorescence, and reverse transcription polymerase chain reaction (RT-PCR) were carried out to assess cell injury, oxidative stress, in ammation, and apoptosis. The TQ formulation showed good in vitro characteristics, including stable nanoparticle structure and size with high drug release rate. In vivo determinations revealed that TQ loaded SNEDDS pre-treatment of rats maintained cellular integrity by decreasing transaminase (ALT and AST) release and preserving the histological characteristics of their liver. The antioxidant ability of the formulation was proven by increased SOD activity, reduced MDA concentration and iNOS protein expression. In addition, this formulation exerted an anti-in ammatory effect evidenced by reduced plasma CRP concentration, MPO activity, gene expressions of TLR-4, TNF-α, NF-κB, and IL-6. Finally, the TQ loaded SNEDDS formulation promoted cell survival by enhancing the Bcl-2/Bax ratio. In conclusion, our results indicate that TQ encapsulated in SNEDDS signi cantly protects rat liver from I/R injury.
This study aims to evaluate the effect of diclofenac addition to the preservation solution Celsior on liver graft preservation. Liver from Wistar rats were cold flushed in situ, harvested and then stored in Celsior solution (24h, 4°C) supplemented or not with 50 mg/L of diclofenac sodium salt. Reperfusion was performed (120 min, 37°C) using the isolated perfusion rat liver model. Perfusate samples were collected to evaluate transaminases activities after cold storage and by the end of reperfusion. In order to evaluate liver function, bile flow, hepatic clearance of bromosulfophthalein and vascular resistance were assessed. Diclofenac scavenging property (DPPH assay) as well as oxidative stress parameters (SOD and MPO activities and the concentration of Glutathione, Conjugated Dienes, MDA and Carbonylated Proteins) were measured. Transcription factors (PPAR-γ and NF-κB), inflammation (COX-2, IL-6, HMGB-1 and TLR-4) as well as apoptosis markers (Bcl-2 and Bax) were determined by quantitative RT-PCR. Enriching the preservation solution Celsior with diclofenac sodium salt attenuated liver injuries and improved graft function. Oxidative stress, inflammation and apoptosis were significantly reduced in Celsior + Diclo solution. Also, diclofenac activated PPAR-γ and inhibited NF-κB transcription factors. In order to lessen graft damage and improve transplant recovery, diclofenac sodium salt may be a promising additive to preservation solution.
In the present study, a self nano-emulsifying drug delivery system (SNEDDS) was developed to evaluate the efficiency of TQ in hepatic ischemia/reperfusion. SNEDDS was pharmaceutically characterized to evaluate droplet size, morphology, zeta potential, thermodynamic stability, and dissolution/diffusion capacity. Animals were orally pre-treated during 10 days with TQ loaded SNEDDS. Biochemical analyses, haematoxylin-eosin staining, indirect immunofluorescence, and reverse transcription polymerase chain reaction (RT-PCR) were carried out to assess cell injury, oxidative stress, inflammation, and apoptosis. The TQ formulation showed good in vitro characteristics, including stable nanoparticle structure and size with high drug release rate. In vivo determinations revealed that TQ loaded SNEDDS pre-treatment of rats maintained cellular integrity by decreasing transaminase (ALT and AST) release and preserving the histological characteristics of their liver. The antioxidant ability of the formulation was proven by increased SOD activity, reduced MDA concentration and iNOS protein expression. In addition, this formulation exerted an anti-inflammatory effect evidenced by reduced plasma CRP concentration, MPO activity, gene expressions of TLR-4, TNF-α, NF-κB, and IL-6. Finally, the TQ loaded SNEDDS formulation promoted cell survival by enhancing the Bcl-2/Bax ratio. In conclusion, our results indicate that TQ encapsulated in SNEDDS significantly protects rat liver from I/R injury.
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