In vitro and in vivo anti-cancer effects of hibernating common carp (Cyprinus carpio) plasma on metastatic triple-negative breast cancer.

Uncontrollable proliferation is a hallmark of cancer cells. Cell proliferation and migration are significantly depressed during hibernation state. Many studies believe some factors in the plasma of hibernating animals cause these effects. This study aimed to assess the anti-cancer effects of hibernating common carp (Cyprinus carpio) plasma on 4T1 cancer cells in vitro and in vivo. The effect of hibernating plasma on cell viability, morphology, migration, apoptosis rate, and cell cycle distribution of 4T1 cells was investigated in vitro and in vivo. Hibernating plasma at a concentration of 16 mg/ml significantly reduced the viability of 4T1 cancer cells, without any toxicity on L929 normal fibroblast cells. It could change the morphology of cancer cells, induced apoptosis and cell cycle arrest at the G2/M phase, and inhibited migration. Furthermore, intratumoral injection of hibernating plasma (200 µl, 16 mg/ml) in the tumor-bearing mice caused a significant inhibition of 4T1 breast tumors volume (46.9%) and weight (58.8%) compared with controls. A significant decrease in the number of metastatic colonies at the lungs (80%) and liver (52.8%) of hibernating plasma-treated animals was detected which increased the survival time (21.9%) compared to the control groups. Immunohistochemical analysis revealed a considerable reduction in the Ki-67-positive cells in the tumor section of the hibernating plasma-treated animals compared with controls. Taken together, the SDS-PAGE and mass spectrometry analysis indicated the alpha-2-macroglobulin level in the hibernating fish plasma was significantly increased. It could exert an anti-cancer effect on breast cancer cells and suggested as a novel cancer treatment strategy.

A multifunctional nanocomposite spray dressing of Kappa-carrageenan-polydopamine modified ZnO/L-glutamic acid for diabetic wounds.

Sprayable bioadhesives with exceptional properties were developed for application in wound healing. In this study, a visible light-crosslinkable nanocomposite bioadhesive hydrogel with multifunctional properties was proposed. While methacrylated Kappa-carrageenan (KaMA), mimicking the natural glycosaminoglycan was applied as the hydrogel matrix, various concentrations of polydopamine modified ZnO (ZnO/PD) nanoparticles (0, 0.5, 1 and 2 wt%) was loaded in it to improve its mechanical, antibacterial and cellular properties. Moreover, L-glutamic acid was incorporated in the nanocomposite hydrogel network to accelerate wound healing. The nanocomposite hydrogels revealed significant mechanical property and recovery ability, comparable elasticity with human skin and great adhesiveness. For instance, the tensile strength of KaMA hydrogel enhanced from 64.1 ± 10 to 80.3 ± 8 kPa and elongation jumped from 20 ± 4% to 61 ± 5% after incorporation of 1 wt% ZnO/PD nanoparticles. The nanocomposite hydrogels demonstrated effectual blood clotting ability and biocompatibility, >95% cell viability after 3 days of incubation. In vivo experiments also suggested that L-glutamic acid loaded nanocomposite hydrogel considerably accelerated wound healing with superior granulation tissue thickness than control in a full-thickness skin defect model. Taken together, this visible-light crosslinking nanocomposite hydrogel with significant properties could be used to spray on a wound area to eliminate wound infection and accelerate wound healing process.

Spirulina extract enriched for Braun-type lipoprotein (Immulina®) for inhibition of 4T1 breast tumors' growth and metastasis.

Spirulina platensis extracts have exhibited considerable anti-cancer effects. To investigate the efficacy of the Spirulina extract enriched for Braun-type lipoprotein (Immulina®) for breast cancer treatment, 4T1 breast tumor-bearing mice were treated with 40 mg/kg Immulina® daily and the tumors' growth and metastasis were assessed. Also, CD4, CD8, and CD56 staining were performed to investigate the Immulina® effect on the immune cells' recruitment to the tumors by immunohistochemistry. Immulina® could significantly (P < 0.001) inhibit 4T1 breast tumors' growth. Immulina®-treated group exhibited a 63% decrease in the tumors' volume in comparison with control (P < 0.001). Also, Immulina® could significantly (P < 0.001) decrease metastatic burden at the vital organs as 68% and 61% decrease in the liver and lungs metastatic colonies were observed, respectively. Also, Immulina® could increase mean survival time of the tumor-bearing mice for 29 days. The Spirulina-treated mice tumors contained significantly more infiltrated NK, CD4+, and CD8+ T lymphocytes in comparison with control. Taking together, Immulina® can be a safe anti-cancer supplement with the ability to cause direct apoptosis to the cancer cells and activate the immune system against tumor. This supplement with natural origin seems to have bright future to help breast cancer patients.

C-phycocyanin: a natural product with radiosensitizing property for enhancement of colon cancer radiation therapy efficacy through inhibition of COX-2 expression.

Different chemical and nanomaterial agents have been introduced for radiosensitizing purposes. However, many researchers believe these agents are far away from clinical application due to side effects and limited knowledge about their behavior in the human body. In this study, C-phycocyanin (C-PC) was used as a natural radiosensitizer for enhancement of radiation therapy (RT) efficacy. C-PC treatment's effect on the COX-2 expression of cancer cells was investigated by flow cytometry, western blot, qRT-PCR analyses in vitro and in vivo. Subsequently, the radiosensitizing effect of C-PC treatment was investigated by MTT and clonogenic cell survival assays for CT-26, DLD-1, HT-29 colon cancer cell lines and the CRL-1831 as normal colonic cells. In addition, the C-PC treatment effect on the radiation therapy efficacy was evaluated according to CT-26 tumor's growth progression and immunohistochemistry analyses of Ki-67 labeling index. C-PC treatment (200 µg/mL) could significantly enhance the radiation therapy efficacy in vitro and in vivo. Synergistic interaction was detected at C-PC and radiation beams co-treatment based on Chou and Talalay formula (combination index <1), especially at 200 µg/mL C-PC and 6 Gy radiation dosages. The acquired DEF of C-PC treatment was 1.39, 1.4, 1.63, and 1.05 for CT-26, DLD-1, HT-29, and CRL-1831 cells, respectively. Also, C-PC + RT treated mice exhibited 35.2% lower mean tumors' volume and about 6 days more survival time in comparison with the RT group (P < 0.05). In addition, C-PC + RT group exhibited 54% lower Ki-67 index in comparison with the RT group. Therefore, C-PC can exhibit high radiosensitizing effects. However, the potential cardiovascular risks of C-PC as a COX-2 inhibitor should be evaluated with extensive preclinical testing before developing this agent for clinical trials.

Immunization using male germ cells and gametes as rich sources of cancer/testis antigens for inhibition of 4T1 breast tumors' growth and metastasis in BALB/c mice.

Recently cancer/testis antigens (CTA) have gained lots of attention as targets of immune therapy. However, the therapeutic efficacy of the CTAs single-antigen vaccines is not satisfying due to tumor heterogenicity. Therefore, many studies have focused on the enhancement of their efficacy by utilizing rich sources of tumor-associated antigens for anti-cancer vaccination. In the present study, the testicular germ cells and sperm cells as well-known sources of cancer/testis antigens were investigated for anti-4T1 breast cancer vaccination in BALB/c mice. The testicular germ cells (TGCs) and sperm cells were isolated from male BALB/c mice. The definite number of cells were homogenized and mixed with Bacillus Calmette-Guerin (BCG) for vaccination of female BALB/c mice. The treatment groups underwent 3 times of immunizations with one-week intervals and one week after the last injection, all groups were injected with 4T1 cancer cells. The TGCs + BCG (259.7 ±â€¯39 mm3) and Sperm + BCG (426 ±â€¯52 mm3) groups exhibited a significant decrease in the tumors' volume in comparison with BCG (641.3 ±â€¯102 mm3) and no-treatment (788.1 ±â€¯117 mm3) groups. Therefore, the TGCs + BCG immunized mice had the smallest tumors in comparison with all groups (P < 0.05). Also, the vital organs of TGCs + BCG (lungs: 6.8 ±â€¯2, liver: 10.1 ±â€¯2) immunized mice exhibited lowest metastatic burden in comparison with the Sperm + BCG (lungs: 13.5 ±â€¯3, liver: 21.1 ±â€¯4), BCG (lungs: 24.3 ±â€¯4, liver: 33 ±â€¯4), and no-treatment (lungs: 26.5 ±â€¯6, liver: 37.3 ±â€¯3) groups. These observations were inconsistent with the tumor-bearing mice survival evaluations as the TGCs + BCG group had longer mean survival time (79.6 ±â€¯12 days) in comparison with other groups (no-treatment: 49.8 ±â€¯8, BCG: 50.5 ±â€¯10, BCG + Sperm: 64.6 ±â€¯7 days). Therefore, TGCs can be a potential source of antigens for the anti-breast cancer immunization and more investigations are necessary.

Induction of Tyrosine Hydroxylase Gene Expression in Embryonal Carcinoma Stem Cells Using a Natural Tissue-Specific Inducer.

A large number of studies have focused on the generation of dopaminergic neurons from pluripotent cells. Differentiation of stem cells into distinct cell types is influenced by tissue-specific microenvironment. Since, central nervous system undergoes further development during postnatal life, in the present study neonatal rat brain tissue extract (NRBE) was applied to direct the differentiation of embryonal carcinoma stem cell line, P19 into dopaminergic (DA) phenotypes. Additionally, a neuroprotective drug, deprenyl was used alone or in combination with the extract. Results from morphological, immunofluorescence, and qPCR analyses showed that during a period of one to three weeks, a large percentage of stem cells were differentiated into neural cells. The results also indicated the greater effect of NRBE on the differentiation of the cells into tyrosine hydroxylase-expressing cells. MS analysis of NRBE showed the enrichment of gene ontology terms related to cell differentiation and neurogenesis. Network analysis of the studied genes and some DA markers resulted in the suggestion of potential regulatory candidates such as AVP, ACHE, LHFPL5, and DLK1 genes. In conclusion, NRBE as a natural native inducer was apparently able to simulate the brain microenvironment and support neural differentiation of P19 cells.

In vitro and in vivo performance of a propolis-coated polyurethane wound dressing with high porosity and antibacterial efficacy.

Wound dressings with antimicrobial and wound healing accelerating properties are emerging as valuable options to prevent wound infection and improve the wound healing process. In this study, high porous polyurethane (PU) foams were successfully prepared using salt leaching/solvent casting method and were coated with propolis as a well-known anti-bacterial agent. The wound dressings were subjected to detail analyzes using electron microscopy, reflectance Fourier transform infrared spectroscopy, mechanical properties, contact angle measurement, ratio swelling, porosity measurement, and in vitro and in vivo evaluations. The prepared wound dressings had high porosity (more than 80%) with homogeneous pore structure and sufficient interconnectivity. The increase of propolis concentration (10%-30%) caused tensile strength decrease (5.26 ± 0.40-2.99 ± 0.11 MPa), elongation at break increase (372 ± 12-434 ± 22%), contact angle decrease (114.52 ± 2.31° to 35.53 ± 1.65°), water absorption decreased (243 ± 15-207 ± 14%) and enhancement of the antibacterial activity against Escherichia coli and Staphylococcus aureus. The propolis coated wound dressing exhibited significant enhancement of in vitro cellular compatibility and in vivo wound healing which had direct relative with coated propolis concentration. Therefore, propolis-coated polyurethane wound dressing can be an appropriate candidate for more pre-clinical investigations.

The combined effects of three-dimensional cell culture and natural tissue extract on neural differentiation of P19 embryonal carcinoma stem cells.

Tissue engineering, as a novel transplantation therapy, aims to create biomaterial scaffolds resembling the extracellular matrix in order to regenerate the damaged tissues. Adding bioactive factors to the scaffold would improve cell-tissue interactions. In this study, the effect of chitosan polyvinyl alcohol nanofibres containing carbon nanotube scaffold with or without active bioglass (BG+ /BG- ), in combination with neonatal rat brain extract on cell viability, proliferation, and neural differentiation of P19 embryonic carcinoma stem cells was investigated. To induce differentiation, the cells were cultured in α-MEM supplemented with neonatal rat brain extract on the scaffolds. The expression of undifferentiated stem cell markers as well as neuroepithelial and neural-specific markers was evaluated and confirmed by real-time Reverse transcription polymerase chain reaction (RT-PCR) and immunofluorescence procedures. Finally, the three-dimensional (3D) cultured cells were implanted into the damaged neural tubes of chick embryos, and their fates were followed in ovo. Based on the histological and immunofluorescence observations, the transplanted cells were able to survive, migrate, and penetrate into the host embryonic tissues. Gene network analysis suggested the possible involvement of neurotransmitters as a downstream target of synaptophysin and tyrosine hydroxylase. Overall, the results of this study indicated that combining the effects of 3D cell culture and natural brain tissue extract can accelerate the differentiation of P19 embryonic carcinoma cells into neuronal phenotype cells.

Effects of Silver Nanoparticle on the Developing Liver of Rat Pups after Maternal Exposure.

The extensive application of silver nanoparticles (AgNPs) has been increased due to their antimicrobial properties, however numerous concerns has been arisen about their toxicity potential. Since nanoparticles can cross through the placenta and accumulate in the embryonic organs especially liver, in this study, developmental hepatotoxicity of AgNPs was investigated. Pregnant rats were divided into two groups, vehicle control group and treated group. Treated group received AgNPs (25 mg/Kg) through intra-gastric gavage in a period of gestational days 1-19. Pups were sacrificed after the birth and their livers collected. Histopathology, ICP- mass spectrometry, Spectrophotometric assay, and ELISA were employed to evaluate AgNPs toxicity in the liver of pups. Glutathione peroxidase (GPX) activity and glutathione (GSH) level were significantly decreased and malondialdehyde (MDA) and caspase 9 levels were significantly increased, although there was no significant change in caspase 8 content in the liver of offspring. Fatty degeneration and congested dilated sinusoids were also observed in histo-pathological examination. These results suggest that maternal oral exposure to AgNPs may induce oxidative stress and apoptosis in the liver of their offspring. Further investigations are required to clarify molecular events behind this happening.

Wound healing properties of PVA/starch/chitosan hydrogel membranes with nano Zinc oxide as antibacterial wound dressing material.

In this work, hydrogel membranes were developed based on poly vinyl alcohol (PVA), starch (St), and chitosan (Cs) hydrogels with nano Zinc oxide (nZnO). PVA/St/Cs/nZnO hydrogel membranes were prepared by freezing-thawing cycles, and the aqueous PVA/St solutions were prepared by dissolving PVA in distilled water. After the dissolution of PVA, starch was mixed, and the mixture was stirred. Then, chitosan powder was added into acetic acid, and the mixture was stirred to form a chitosan solution. Subsequently, Cs, St and PVA solutions were blended together to form a homogeneous PVA/St/Cs ternary blend solution. Measurement of Equilibrium Swelling Ratio (ESR), Water Vapor Transmission Test (WVTR), mechanical properties, scanning electron microscopy (SEM), MTT [3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyl tetrazolium bromide] assay, antibacterial studies, in vivo wound healing effect and histopathology of the hydrogel membranes were then performed. The examination revealed that the hydrogel membranes were more effective as a wound dressing in the early stages of wound healing and that the gel could be used in topic applications requiring a large spectrum of antibacterial activity; namely, as a bandage for wound dressing.

Effects of A 4-Week Aerobic Exercise on Lipid Profile and Expression of LXRα in Rat Liver.

OBJECTIVE: Liver X receptors (LXRs) are ligand-activated transcription factors of the nuclear hormonal receptor superfamily which modulate the expression of genes involved in cholesterol homeostasis. Hence, further unraveling of the molecular function of this gene may be helpful in preventing cardiovascular diseases. MATERIALS AND METHODS: This experimental intervention study included twelve adult Wistar male rats (12-14 weeks old, 200-220 g) which were divided into the control (n=6) and training (n=6) groups. The training group received exercise on a motor-driven treadmill at 28 meters/minute (0% grade) for 60 minutes a day, 5 days a week for 4 weeks. Rats were sacrificed 24 hours after the last session of exercise. A portion of the liver was excised, immediately washed in ice-cold saline and frozen in liquid nitrogen for extraction of total RNA. Plasma was collected for high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), total cholesterol (TC) and triglycerides (TG) measurements. All variables were compared by independent t test. RESULTS: A significant increase in LXRα transcript level was observed in trained rats (P<0.01). Plasma HDL-C concentration was also significantly higher (P<0.01) in trained rats. There was a significant decrease in the concentrations of LDL-C (P<0.01) and TC (P<0.02), and the ratios of TC/HDL-C (P<0.001) and LDL/HDL-C (P<0.002) in trained rats. However, the TG concentration was unchanged (P>0.05). CONCLUSION: We found that endurance training induces significant elevation in LXRα gene expression and plasma HDL-C concentration resulting in depletion of the cellular cholesterol. Therefore, it seems that a contributor to the positive effects of exercise in cardiovascular disease prevention is through the expression of LXRα, which is a key step in reverse cholesterol transport.

Overexpression of SORCIN is a Prognostic Biomarker for Multidrug-Resistant Pediatric Acute Lymphoblastic Leukemia and Correlates with Upregulated MDR1/P-gp.

BACKGROUND: Multidrug resistance is one of the major causes of treatment failure in pediatric acute lymphoblastic leukemia (ALL), and SORCIN is an intracellular calcium modulator protein. The current study was designed to investigate the in vitro and in vivo relationships between the expression levels of SORCIN: in tumor cell lines and children with ALL; its possible correlation with MDR1/P-glycoprotein (P-gp), a multidrug resistance-related gene; and response to therapy. MATERIALS AND METHODS: Childhood T-lymphoblastic leukemia (CCRF-CEM) cell lines resistant to methotrexate (MTX) were developed. Patient studies were performed by including 30 children with ALL at diagnosis, 3 children with bone marrow relapse, and 15 children with no symptoms of cancer. The mRNA expression profiles of SORCIN and MDR1/P-gp was assessed using quantitative polymerase chain reaction (qPCR). Minimal residual disease (MRD) was measured in the patient population, a year following the initial therapy using qPCR. RESULTS: Cell line data analyses showed a positive correlation between SORCIN mRNA levels and resistance to MTX. The difference between patient and control groups for SORCIN expression levels was not significant. However, patients with a negative response to therapy showed an increase in SORCIN mRNA levels (up to 6.8-fold) compared with those with negative MRD. In addition, the results demonstrated a significant positive correlation between SORCIN and MDR1/P-gp gene expression levels. CONCLUSION: The current study introduces, for the first time, a possible prognostic value of SORCIN in childhood ALL, which may be correlated with MDR1/P-gp gene expression in these patients.

Effect of Nanosilver Particles on Procaspase-3 Expression in Newborn Rat Brain.

OBJECTIVE: Nanotechnology focuses on materials having at least one dimension of less than 100 nanometers. Nanomaterials such as Nanosilver (NS) have unique physical and chemical properties such as size, shape, surface charge. NS particles are thought to in- duce neuronal degeneration and necrosis in the brain. It has been reported that NS parti- cles generate free radicals and oxidative stress which alters gene expression and induces apoptosis. This study was designed to evaluate whether the detrimental effect of NS parti- cles is through the activation of Procaspase-3 during fetal neural development. MATERIALS AND METHODS: In this experimental study, thirty Wistar female rats at day one of pregnancy were semi-randomly distributed into three groups of ten. Group 1, the control group, had no treatment. From day 1 to the end of pregnancy, groups 2 and 3 received 1 and 10 ppm NS respectively via drinking water. Newborn rats were sacrificed immediately after birth and their brains were dissected and kept frozen. Total RNA, extracted from brain homogenates, was reverse transcribed to cDNA. Quantitative real-time polymerase chain reaction (PCR) analysis was undertaken to estimate the expression level of Procaspase-3. RESULTS: Developmental exposure to NS induced neurotoxicity and apoptosis. This corre- lated with a significant increase in Procaspase-3 expression level especially at 10 ppm NS. CONCLUSION: The pro-apoptotic activity of NS in cells is likely to due to the dysregula- tion of Procaspase-3.

mRNA expression profile of multidrug-resistant genes in acute lymphoblastic leukemia of children, a prognostic value for ABCA3 and ABCA2.

Multidrug resistance (MDR) is an important cause of treatment failure in acute lymphoblastic leukemia (ALL). The ABC family of membrane transporters is proposed, albeit with controversy, to be involved in this process. The present study aims to investigate the mRNA expression profile of several genes of this family, including ABCA2, ABCA3, ABCB1/MDR1, MRP1/ABCC1, MRP3/ABCC3, ABCG2/BCRP, and the intracellular transporter MVP/LRP, in childhood ALL, and to evaluate their association with response to therapy. Some genes in the present research are being studied for the first time in Iran. Using quantitative real-time PCR, we evaluated 27 children with ALL at diagnosis and 15 children with normal bone marrow. The status of response to therapy was assessed one year after the onset of therapy through investigating the IgH/TCRγ gene rearrangements. Our findings indicate a considerable and direct relationship between mRNA expression levels of ABCA2, ABCA3, MDR1, and MRP1 genes and positive minimal residual disease (MRD) measured after one year of treatment. Statistical analysis revealed that expression of these genes higher than the cutoff point will raise the risk of MRD by 15-, 6.25-, 12-, and 9-fold, respectively. No relationship was found between of MVP/LRP, MRP3 and ABCG2 genes expression and ALL prognoses. Considering the direct and significant relationship between the increased expression of ABCA2, ABCA3, MDR1, and MRP1 genes and positive risk of MRD in children with ALL, evaluating the expression profile of these genes on diagnosis may identify high risk individuals and help plan a more efficient treatment strategy.

Endurance training enhances LXRα gene expression in Wistar male rats.

Liver X receptor α (LXRα) is a member of the ligand-activated transcription factor of nuclear hormonal receptor superfamily, whose activation leads to modulation in the expression of genes involved in cholesterol homeostasis including ATP-binding cassette transporter A1 (ABCA1), which plays a crucial role in plasma high-density lipoprotein cholesterol (HDL-C) remodeling. The purpose of this study was to investigate whether endurance training enhanced the expression level of liver LXRα gene. Twelve adult male Wistar rats (200-220 g) were divided into control and training groups. Training group received exercise on a motor-driven treadmill at 28 m/min (0 % grade) for 60 min/day, 5 days/week for 8 weeks. Twenty-four hours after the last exercise session, the rats were killed and blood was taken from the right ventricle of each rat. Plasma was collected for HDL-C, low-density lipoprotein cholesterol (LDL-C), TC and TG measurements. Furthermore, a portion of the liver of each rat was excised and washed in ice-cold saline and frozen in liquid nitrogen for assessment of LXRα and ABCA1 mRNA levels. Data indicated significant increase in both LXRα and ABCA1 mRNA levels in trained rats, compared to control rats. Plasma HDL-C concentration was significantly higher (P < 0.001) in trained rats at the end of treadmill exercise. However, there was a significant decrease in LDL-C (P < 0.003), TG, TC concentration, TC/HDL-C and LDL/HDL-C ratios in trained rats compared with those in the control group (P < 0.001). In conclusion, we found that endurance training induced significant elevation in LXRα gene expression, which correlated with enhanced levels of ABCA1 mRNA and plasma HDL-C concentration.

Impacts of fresh lime juice and peel on atherosclerosis progression in an animal model.

BACKGROUND: The main protective role of antioxidants in the progression of atherosclerosis has been shown in some studies. Therefore, this project evaluated the effects of Citrus aurantifolia (Christm) juice and peel on antioxidant activity and atherosclerosis progression in rabbits receiving a hypercholesterolemic diet. METHODS: Forty white New Zealand male rabbits were randomly allocated to four groups. All groups were on hypercholesterolemic diet for two months. While the first group was considered as the hypercholesterolemic control, groups 2 and 3 (intervention groups) received 5 ml/day lime juice and 1 g/day dried lime peel powder, respectively. Group 4 was fed a normal diet (normal control). Before and after the study, weight was measured and a fasting blood specimen was taken from the rabbits. Serum lipids analyses and antioxidant activity evaluations were then performed. The rabbits' aorta and coronary arteries were separated and the presence of fatty streaks was studied. RESULTS: Comparing to the hypercholesterolemic control group (-25.2 ± 7.0), only the plasma total antioxidant capacity change was significantly more in rabbits supplemented with lime juice (16.3 ± 14.7) and peel (8.6 ± 7.1) (P = 0.008). The presence of fatty streaks in coronary arteries and aorta of the intervention groups [juice (0.2 ± 0.01); peel (0.0 ± 0.00)] was significantly decreased compared to the hypercholesterolemic control group (1.2 ± 0.4) (P < 0.001). CONCLUSION: Based on our findings, Citrus aurantifolia peel and juice increase plasma antioxidant capacity in rabbits, and can thus prevent or decelerate the process of atherogenesis. However, lime peel is more effective than lime juice.

Antioxidant effects of Citrus aurantifolia (Christm) juice and peel extract on LDL oxidation.

BACKGROUND: We studied the antioxidant effects of fresh juice and peel extract of Citrus aurantifolia (Christm). METHODS: Low density lipoprotein (LDL) was separated from one hypercholesterolemic human serum by modified Bronzert and Brewer procedure. Oxidation of LDL was measured at 234 nm against 0, 5, 10, 20, 25, 30 and 40 µl of fresh lime juice and 0, 5, 10, 15 and 20 µl of peel polyphenolic extract solution in DMSO. RESULTS: 5 µl of lime juice didn't change LDL oxidation. 10 µl of juice inhibited LDL oxidation, and with increasing the juice concentration, LDL was oxidized faster. The higher concentrations of peel extract prevented LDL oxidation better than the lower ones. CONCLUSIONS: Both juice and peel demonstrated antioxidant properties, but the excessive consumption of lime juice seems not to be beneficial. Regarding the intensity and type of flavonoids, lime juice and peel may show different effects.

Liver-protective effects of hydroalcoholic extract of allium hirtifolium boiss. In rats with alloxan-induced diabetes mellitus.

BACKGROUND: Diabetes mellitus is one of the most common endocrine disorders accompanied with many metabolic syndromes. Use of herbal medicines has always been an option to treat a great number of diseases such as diabetes and its complications. In this study the liver-protective effects of hydroalcoholic extract of Allium hirtifolium on liver enzymes level in rats with alloxan-induced diabetes mellitus was investigated. METHODS: Thirty five male rats were randomly divided into five groups of seven; group 1: nondiabetic control, group 2: diabetic control, group 3: diabetic treated with shallot extract (0.1 g/kg), group 4: diabetic rats treated with shallot extract (1 g/kg), and group 5: diabetic treated with glibenclamide (0.6 mg/kg). Using intraperitoneal (IP) injection of alloxan monohydrate, diabetes mellitus was induced in rats. Diabetic rats were treated with intraperitoneal injection for 4 weeks. At the end of the experimental period fasting blood samples were collected. RESULTS: Statistical analysis of the data indicated that hydroalcoholic extract of shallot can significantly decrease serum contents of liver enzymes (ALP, AST, and ALT) in treated groups. In most cases, the effectiveness of the extract on reduction of these enzymes is more than glibenclamide. CONCLUSION: Antioxidant compounds in the extract may recover liver damages caused by free radicals in diabetic rats.