Zoledronic acid-loaded lipidic nanoparticles enhance apoptosis and attenuate invasiveness by inhibiting epithelial to mesenchymal transition (EMT) in HepG2 cancer cells.

The aim of this study was to evaluate the potential of zoledronic acid (ZOL)-loaded lipidic nanoparticles (ZOL-NLCs) in enhancing the efficiency of paclitaxel (Pac) in the context of cytotoxicity, apoptosis, and invasiveness of HepG2 hepatocellular carcinoma cells. ZOL-NLCs were characterized in terms of zeta potential, particle size, and scanning electron microscope (SEM) as well as cell internalization. To measure the anti-proliferative effects of ZOL-NLCs, annexin-V/PI and MTT assays were employed. Real-time PCR and western blot analysis were performed to identify the molecular mechanisms underlying the apoptosis in response to the studied conditions. Furthermore, the transwell migration assay was applied to clarify the role of applied formulations on the invasiveness of HepG2 cells. Our results demonstrated that the optimized ZOL had an average particle size of 105 ± 6 nm with a nearly narrow size distribution. The IC50 values for ZOL and ZOL-NLCs were 90 ± 3.1 and 54.6 ± 2.4 µM, respectively. The population of apoptotic cells was increased from 17 ± 2% to 27 ± 4% (p < 0.05) in response to treatment with ZOL-NLCs. ZOL-loaded nanoparticles triggered the mRNA expression of Bax as pro-apoptotic marker and E-cadherin as epithelial one along with a decrease in mesenchymal marker, N-cadherin, and Bcl-xl as an anti-apoptotic marker in HepG2 cells. These outcomes were consistent with western blot analysis of protein expressions. Besides, ZOL-incorporated lipidic nanoparticles reduced the migration of HepG2 cells significantly. Our data suggest that the formulation of ZOL into lipidic nanoparticles can be considered a potential therapeutic approach that can enhance the efficacy of Pac chemotherapy.

Protective effects of Gamma Oryzanol on distant organs after kidney ischemia-reperfusion in rats: A focus on liver protection.

BACKGROUND: Acute kidney injury (AKI) is the main clinical concern resulted from ischemia-reperfusion injury (IRI). Ample clinical data indicates that AKI is associated with distant organ dysfunctions and poor patients' outcomes. Oxidative stress and inflammation have a critical role in the pathogenesis of organ injuries following IRI. The objectives of this study were to determine the impact of Gamma Oryzanol (GO), extracted from rice bran oil, on distant organs in rats after IRI. METHODS: Twelve out of 24 Wistar rats were treated by one dosage of GO (100mg/kg) 1 h before I/R induction through both oral gavage and intraperitoneal injection. Then, the AKI model rats were induced by IRI. Oxidative stress and antioxidant protein levels were assessed in the brain, heart, and liver tissues in the experimental groups. Furthermore, the effects of GO on IRI-induced liver dysfunction, apoptosis, and inflammation were measured by Western blot. RESULTS: GO pretreatment could significantly restore the levels and activity of antioxidant proteins in the brain, heart, and liver tissues (P < 0.05). Moreover, GO pretreatment could decrease the inflammatory cytokine (IL-1, IL-6, and TNF-α) in the liver (P < 0.01). By reducing Bax/Bcl-2 ratio and down-regulating caspase-3, GO could significantly diminish apoptosis in the liver tissue after the kidney I/R (P < 0.01). Additionally, GO could significantly diminish the deterioration of liver function in the kidney I/R model. CONCLUSION: GO protects distant organs against renal IRI-induced oxidative stress. Furthermore, it ameliorates liver function and remarkably exerts anti-oxidative, anti-inflammatory, and anti-apoptotic roles in the liver as an important detoxifying organ.