The beneficial roles of Lupineus luteus and lifestyle changes in management of metabolic syndrome: A case study

Metabolic syndrome (MetS) is a cluster of cardiovascular risk factors including obesity, hypertension, dyslipidemia and hyperuricemia. Here, we report a 43-year-old man with obesity, hypertension, hypercholesterolemia, hyperuricemia and mild liver dysfunctions. Lupid (Lupineus luteus) and therapeutic lifestyle change (TLC) were suggested as therapeutic intervention for the present case for 6 months. The body weight, body mass index (BMI), blood pressure, total cholesterol (TC), low density lipoprotein-cholesterol (LDL-C), triacylglycerol (TAG), uric acid (UA) and alanine transaminase (ALT) were markedly decreased by 26.85%, 26.95%, 13%, 53.84%, 57.84%, 36.14%, 47.58% and 61.62% respectively, compared to those at baselines. However, high density lipoprotein cholesterol (HDL-C) value was markedly increased by 30.77%. The present results concluded that administration of lupin with TLC is good intervention for prevention and treatment of MetS.     

Gene expression of IQGAPs and Ras families in an experimental mouse model for hepatocellular carcinoma: a mechanistic study of cancer progression

IQGAPs genes play critical role in either induction or suppression of cancer and its progression, however the relationship between Ras genes and these genes are still unclear. In this study, we tried to understand the mechanistic action of IQGAPs genes and its correlation with Ras genes in mouse hepatic cancer model. The genetic expressions of IQGAP1, IQGAP2, IQGAP3, Hras, Kras, Nras, Mras, Caspase3, and BAX were followed in both hepatocellular carcinoma and normal liver cells of Balbc mice. Genotoxic agent diethylnitrosamine (DEN)-induced hepatic cancer model was induced in male mice and recorded the occurrence of hepatocellular carcinoma by morphological and histological changes in the liver. It was observed that mRNA expressions of IQGAP1, Hras, Kras, Nras, Mras, Caspase3, and BAX genes were highly elevated in hepatocellular carcinoma cells when compared with normal liver cells, additionally their expressions increased by concentrating the dose of DEN. While, the expressions of IQGAP2 and IQGAP3 were significantly decreased in hepatocellular carcinoma cells when compared with normal liver cells, as well as their expressions decreased more with increasing the dose of DEN. It was concluded from this study that IQGAP1 has a strong signaling relationship with Ras genes in induction of cancer and it is considered as a key gene for induction or suppression of the hepatocellular carcinoma.     

Erythrocyte-mediated delivery of pravastatin: In Vitro study of effect of hypotonic lysis on biochemical parameters and loading efficiency

Exposure of erythrocytes to hypotonic lysis creates pores in the cell membrane, through which pravastatin can enter and become trapped, after resealing them with a suitable buffer. We investigated the effects of tonicity, incubation time and drug concentration on drug loading into erythrocytes. Furthermore, we investigate the effects of pravastatin on erythrocyte oxidative stress markers and osmotic fragility behavior. Encapsulation was achieved using buffer solutions of different tonicities (0.5, 0.6 and 0.7% NaCl) and different drug concentrations (2, 4, 8 and 10 mg/mL) for a range of incubation times (15, 30, 60 and 120 min). The results demonstrated that controlled hypotonic lysis could entrap pravastatin in human erythrocytes, with acceptable loading parameters. The highest loading (34%) was achieved at 0.6% NaCl and 10 mg/mL pravastatin for 60 min incubation. At this pravastatin concentration, oxidative stress markers were similar to those seen in controls, and fragility and hematological parameters were unaffected in drug-loaded erythrocytes. These results indicate that the loading process and pravastatin concentration had no deleterious effects on the structure of pravastatin-loaded erythrocytes, suggesting that they may therefore have a similar life span to normal cells. Pravastatin-loaded erythrocytes may thus provide an effective extended-release-delivery system for pravastatin.     

Biochemically altered human erythrocytes as a carrier for targeted delivery of primaquine: an <Emphasis Type="Italic">In Vitro</Emphasis> study

The aim of this study was to investigate human erythrocytes as a carrier for targeted drug delivery of primaquine (PQ). The process of PQ loading in human erythrocytes, as well as the effect of PQ loading on the oxidative status of erythrocytes, was also studied. At PQ concentrations of 2, 4, 6, and 8 mg/mL and an incubation time of 2 h, the ratios of the concentrations of PQ entrapped in erythrocytes to that in the incubation medium were 0.515, 0.688, 0.697 and 0.788, respectively. The maximal decline of erythrocyte reduced glutathione content was observed at 8 mg/mL of PQ compared with native erythrocytes p < 0.001. In contrast, malondialdehyde and protein carbonyl were significantly increased in cells loaded with PQ (p < 0.001). Furthermore, osmotic fragility of PQ carrier erythrocytes was increased in comparison with unloaded cells. Electron microscopy revealed spherocyte formation with PQ carrier erythrocytes. PQ-loaded cells showed sustained drug release over a 48 h period. Erythrocytes were loaded with PQ successfully, but there were some biochemical as well as physiological changes that resulted from the effect of PQ on the oxidative status of drug-loaded erythrocytes. These changes may result in favorable targeting of PQ-loaded cells to reticulo-endothelial organs. The relative impact of these changes remains to be explored in ongoing animal studies.     

Erythrocyte nitric oxide synthase as a surrogate marker for mercury‐induced vascular damage: The modulatory effects of naringin

In this study, endothelial nitric oxide synthase activity and nitric oxide (NO) production by human erythrocytes in the presence and absence of mercuric chloride (HgCl₂), L ‐arginine (L ‐ARG), ‐ nitro‐L ‐arginine methyl ester (L ‐NAME), and naringin (NAR) were investigated. In addition, the levels of reduced glutathione (GSH) and related enzymes were estimated in erythrocytes hemolysate. The protein carbonyl content (PCC) and thiobarbituric acid‐reactive substances (TBARS) levels were also determined. The results of this study revealed that the treatment of erythrocytes with either HgCl₂ or L ‐NAME induced a significant decrease in NOS activity and nitrite levels compared with control cells. Furthermore, mercury exposure significantly increased the levels of PCC and TBARS but reduced the GSH level. The activities of glucose‐6‐phosphate dehydrogenase, glutathione reductase, glutathione peroxidase, and glutathione‐S‐transferase (GST) were inhibited. The exposure of erythrocytes to HgCl₂ in combination with L ‐ARG, NAR, or both ameliorated the investigated parameters compared with erythrocytes incubated with HgCl₂ alone. These results indicate that mercury exposure decreased both erythrocyte NOS activity and nitrite production, and that these parameters might be indicative of mercury exposure. The data also suggest that concomitant treatment with NAR can restore NO bioavailability through either its metal‐chelating properties or its antioxidant activity. © 2013 Wiley Periodicals, Inc. Environ Toxicol 29: 1314–1322, 2014.     

The use of chitosan-coated flexible liposomes as a remarkable carrier to enhance the antitumor efficacy of 5-fluorouracil against colorectal cancer

Surface-coated nanocarriers have been extensively used to enhance the delivery of anticancer drugs and improve their therapeutic index. In this study, chitosan (CS)-coated flexible liposomes (chitosomes) containing 5-fluorouracil (5-FU) were designed and characterized for use as a novel approach to target colon cancer cells. 5-FU-loaded flexible liposomes (F1, F2, and F3) and 5-FU-loaded chitosomes (F4, F5, and F6) were prepared using film hydration and electrostatic deposition techniques, respectively. The particle size, polydispersity index (PDI), zeta potential, entrapment efficiency (EE%), morphology, and in vitro drug release ability, and cytotoxicity of the formulations were determined. The results revealed that the size of chitosomes ranged from 212 to 271 nm with a positive surface charge of 6.1 to 14.7 mV, whereas the particle size of liposomes ranged from 108 to 234 nm with negative surface charges of ?2.3 to ?16.3. F3 and F6 had a spherical shape with a rough surface structure. The in vitro drug release study revealed that chitosomes retard 5-FU release as opposed to the 5-FU solution and liposomes. The cytotoxicity study using a colon cancer cell line (HT-29) showed that 5-FU-loaded chitosomes were more effective in killing cancer cells in a sustained manner than liposomes and the 5-FU solution. Chitosomes were therefore successfully developed as nanocarriers of 5-FU, with potential cytotoxicity for colorectal cancer cells.     

Engineering erythrocytes as a novel carrier for the targeted delivery of the anticancer drug paclitaxel

Paclitaxel (PTX) is formulated in a mixture of Cremophor EL and dehydrated alcohol. The intravenous administration of this formula is associated with a risk of infection and hypersensitivity reactions. The presence of Cremophor EL as a pharmaceutical vehicle contributes to these effects. Therefore, in this study, we used human erythrocytes, instead of Cremophor, as a pharmaceutical vehicle. PTX was loaded into erythrocytes using the preswelling method. Analysis of the obtained data indicates that 148.8 μg of PTX was loaded/mL erythrocytes, with an entrapment efficiency of 46.36% and a cell recovery of 75.94%. Furthermore, we observed a significant increase in the mean cell volume values of the erythrocytes, whereas both the mean cell hemoglobin and the mean cell hemoglobin concentration decreased following the loading of PTX. The turbulence fragility index values for unloaded, sham-loaded and PTX-loaded erythrocytes were 3, 2, and 1 h, respectively. Additionally, the erythrocyte glutathione level decreased after PTX loading, whereas lipid peroxidation and protein oxidation increased. The release of PTX from loaded erythrocytes followed first-order kinetics, and about 81% of the loaded drug was released into the plasma after 48 h. The results of the present study revealed that PTX was loaded successfully into human erythrocytes with acceptable loading parameters and with some oxidative modification to the erythrocytes.     

Low density lipoprotein bionanoparticles: From cholesterol transport to delivery of anti-cancer drugs

In this review article, we highlight the importance of low-density lipoprotein (LDL) and its implications in the field of drug delivery to cancer cells. LDL is naturally occurring bionanoparticles (BNP) with a size of 18–25 nm. These BNPs specifically transport cholesterol to cells expressing the LDL receptors (LDLRs). Several tumors overexpress LDLRs, presumably to provide cholesterol for sustaining a high rate of membrane synthesis. LDL BNPs are biocompatible and biodegradable, favorably bind hydrophobic and amphiphilic drugs, are taken up by a receptor-mediated mechanism, have a half-life of 2–4 days, and can be rerouted. Drugs can be loaded onto LDL BNPs by surface loading, core loading, and apoprotein interaction. LDL may be used as a drug carrier for treatment of atherosclerosis, cancer, and in photodynamic therapies.     

Pravastatin chitosan nanogels-loaded erythrocytes as a new delivery strategy for targeting liver cancer

Chitosan nanogels (CNG) are developed as one of the most promising carriers for cancer targeting. However, these carriers are rapidly eliminated from circulation by reticuloendothelial system (RES), which limits their application. Therefore, erythrocytes (ER) loaded CNG as multifunctional carrier may overcome the massive elimination of nanocarriers by RES. In this study, erythrocytes loaded pravastatin–chitosan nanogels (PR–CNG–ER) were utilized as a novel drug carrier to target liver cancer. Thus, PR–CNG formula was developed in nanosize, with good entrapment efficiency, drug loading and sustained release over 48 h. Then, PR–CNG loaded into ER were prepared by hypotonic preswelling technique. The resulting PR–CNG–ER showed 36.85% of entrapment efficiency, 66.82% of cell recovery and release consistent to that of hemoglobin over 48 h. Moreover, PR–CNG–ER exhibited negative zeta potential, increasing of hemolysis percent, marked phosphatidylserine exposure and stomatocytes shape compared to control unloaded erythrocytes. PR–CNG–ER reduced cells viability of HepG2 cells line by 28% compared to unloaded erythrocytes (UER). These results concluded that PR–CNG–ER are promising drug carriers to target liver cancer.     

Protective effect of pravastatin against mercury induced vascular cells damage: Erythrocytes as surrogate markers

In the present study we investigated the protective effect of pravastatin (PRV) against mercury-induced cellular damage. Human erythrocytes were incubated with PRV, HgCl(2) and HgCl(2) pretreated with PRV. Our results revealed that incubation of erythrocytes with HgCl(2) induces a significant increase the ratios of superoxide dismutase/glutathione peroxidase (SOD/GPx), superoxide dismutase/catalase (SOD/CAT), oxidized/reduced glutathione (GSSG/GSH), malondialdehyde(MDA) and protein carbonyl(PCO) by 60%, 50%, 333%, 400% and 208% respectively. Whereas, prior incubation of erythrocytes with PRV maintains these parameters at values similar to control cells. Furthermore, the level of nitrite in erythrocytes decreases significantly on treatment with HgCl(2), whereas it remains similar to the control when pretreated with PRV. Also, there was an increase in erythrocytes hemolysis when treated with HgCl(2), whereas it remained the like to the control when pretreated with PRV. In conclusion, PRV pretreatment maintained the erythrocytes oxidant/antioxidant balance and nitrite level during mercury exposure. Consequently, PRV pretreatment is worthy of further investigation in the reduction of the cardiovascular risk of mercury.