Uvaol ameliorates lipid deposition in hyperlipidemic hepatocytes by suppressing protein-tyrosine phosphatase 1B/ER stress signaling.

Uvaol (UV), a pentacyclic triterpene found in olives and virgin olive oil, is known for its anti-inflammatory and antioxidant effects in various disease models. While olive oil is reported to reduce obesity and insulin resistance, the specific impact of UV on liver lipid metabolism and its molecular mechanisms are not fully understood. In this study, hepatic lipid accumulation was measured using oil red O staining, and protein expression levels in liver cells were assessed via Western blot analysis. Apoptosis was evaluated through cell viability and caspase 3 activity assays. UV treatment reduced lipid accumulation, fatty acid uptake, apoptosis, and ER stress in palmitate-treated liver cells. Additionally, UV enhanced fatty acid oxidation. Mechanistically, increased SIRT6 expression and autophagy were observed in UV-treated cells. SIRT6-targeted siRNA or 3-methyladenine blocked the effects of UV in hyperlipidemic cells. In conclusion, UV improves SIRT6/autophagy signaling, reducing lipid deposition and apoptosis in liver cells under high lipid conditions. This in vitro study provides strong evidence for potential therapeutic strategies for hepatic steatosis.

The Role of Immunomodulator Betaleukin in Recovery of Hepatocytic Ploidy Profile in Delayed Terms after Irradiation.

We studied the radioprotective effect of betaleukin administered to (CBA×C57Bl/6)F1 mice in single doses of 50 and 3 µg/kg 2 and 22 h, respectively, prior to long-term (21 h) whole-body low-intensity (10 mGy/min) γ-radiation (137Сs; total dose 12.65 Gy). Hepatocyte ploidy, a biomarker of metabolic disorders of the liver, was evaluated, and nuclearity and ploidy indices were calculated. In 10 months after irradiation, a significant decrease in the ploidy index was revealed in the group of irradiated mice, while in animal receiving 3 or 50 µg/kg betaleukin, this parameter did not differ and even surpassed the control level, respectively. Thus, in vivo assessment of hepatocytic ploidy profile in mice revealed negative delayed effects of γ-irradiation in a dose of 12.65 Gy and a protective effect a single injection of immunomodulator betaleukin.

Radiation-primed hepatocyte transplantation in murine monogeneic dyslipidemia normalizes cholesterol and prevents atherosclerosis.

BACKGROUND & AIMS: Inherited abnormalities in apolipoprotein E (ApoE) or low-density lipoprotein receptor (LDLR) function result in early onset cardiovascular disease and death. Currently, the only curative therapy available is liver transplantation. Hepatocyte transplantation is a potential alternative; however, physiological levels of hepatocyte engraftment and repopulation require transplanted cells to have a competitive proliferative advantage of over host hepatocytes. Herein, we aimed to test the efficacy and safety of a novel preparative regimen for hepatocyte transplantation. METHODS: Herein, we used an ApoE-deficient mouse model to test the efficacy of a new regimen for hepatocyte transplantation. We used image-guided external-beam hepatic irradiation targeting the median and right lobes of the liver to enhance cell transplant engraftment. This was combined with administration of the hepatic mitogen GC-1, a thyroid hormone receptor-ß agonist mimetic, which was used to promote repopulation. RESULTS: The non-invasive preparative regimen of hepatic irradiation and GC-1 was well-tolerated in ApoE-/- mice. This regimen led to robust liver repopulation by transplanted hepatocytes, which was associated with significant reductions in serum cholesterol levels after transplantation. Additionally, in mice receiving this regimen, ApoE was detected in the circulation 4 weeks after treatment and did not induce an immunological response. Importantly, the normalization of serum cholesterol prevented the formation of atherosclerotic plaques in this model. CONCLUSIONS: Significant hepatic repopulation and the cure of dyslipidemia in this model, using a novel and well-tolerated preparative regimen, demonstrate the clinical potential of applying this method to the treatment of inherited metabolic diseases of the liver. LAY SUMMARY: Hepatocyte transplantation is a promising alternative to liver transplantation for the treatment of liver diseases. However, it is inefficient, as restricted growth of transplanted cells in the liver limits its therapeutic benefits. Preparative treatments improve the efficiency of this procedure, but no clinically-feasible options are currently available. In this study we develop a novel well-tolerated preparative treatment to improve growth of cells in the liver and then demonstrate that this treatment completely cures an inherited lipid disorder in a mouse model.

Protective Effect of Antrodia cinnamomea Extract against Irradiation-Induced Acute Hepatitis.

Radiotherapy for treatment of hepatocellular carcinoma causes severe side effects, including acute hepatitis and chronic fibrosis. Complementary and alternative medicine (CAM) has emerged as an important part of integrative medicine in the management of diseases. Antrodia cinnamomea (AC), a valuable medicinal fungus originally found only in Taiwan, has been shown to possess anti-oxidation, vaso-relaxtation, anti-inflammation, anti-hepatitis, and anti-cancer effects. In this paper we evaluate the protective effects of ethanol extract of Antrodia cinnamomea (ACE) against radiotoxicity both in normal liver cell line CL48 and in tumor-bearing mice. In CL48, ACE protects cells by eliminating irradiation-induced reactive oxygen species (ROS) through the induction of Nrf2 and the downstream redox system enzymes. The protective effect of ACE was also demonstrated in tumor-bearing mice by alleviating irradiation-induced acute hepatitis. ACE could also protect mice from CCl4-induced hepatitis. Since both radiation and CCl4 cause free radicals, these results indicate that ACE likely contains active components that protect normal liver cells from free radical attack and can potentially benefit hepatocellular carcinoma (HCC) patients during radiotherapy.

The LncRNA H19/miR-193a-3p axis modifies the radio-resistance and chemotherapeutic tolerance of hepatocellular carcinoma cells by targeting PSEN1.

This study was designated to verify if the lncRNA H19/miR-193a-3p axis would play a regulatory role in the radio-/chemo-resistances of HCC cells through targeting PSEN1. Within the study, five human HCC cell lines were prepared, including Bel-7402, HepG2, Hep3b, QGY-7703, and SMMC-7721. Moreover, docetaxel (DT), paclitaxel (Pt), vinorelbine (Vb), and 5-fluorouracil (5-Fu) were managed as the chemo-therapeutics, and single-dose X-rays were performed as radio-therapies. Besides, lncRNA H19 and miR-193a-3p were detected by qRT-PCR and Western blot were implemented to quantify the expressional levels of PSEN1, Ku80, γ-H2AX, and RAD51. Luciferase reporter gene assay was advanced to verify the targeted relationship between lncRNA H19 and miR-193a-3p. As a consequence, QGY-7703 and Bel-7402 were, respectively, the most radiation-sensitive and radiation-proof cell lines, and Bel-7402 was associated with the highest resistances to DT, Pt, Vb, and 5-FU. The restrained lncRNA H19 and over-expressed miR-193a-3p expressions tended to significantly elevate the survival rate and proliferation of Bel-7402 cells, when they were exposed to radiation and subject to chemo-therapies. The lncRNA H19 was also found to directly target miR-193a-3p in inducing the HCC development. PSEN1 appeared to be subject to the modification of lncRNA H19 and miR-193a-3p in its acting on the survival rates and proliferative abilities of HCC cells. The lncRNA H19/miR-193a-3p/PSEN1 axis could be regarded as the treatment targets for HCC, so as to further improve the treatment efficacy of chemo- and radio-therapies for HCC.

Long-term effects of low-dose mouse liver irradiation involve ultrastructural and biochemical changes in hepatocytes that depend on lipid metabolism.

The aim of the study was to investigate long-term effects of radiation on the (ultra)structure and function of the liver in mice. The experiments were conducted on wild-type C57BL/6J and apolipoprotein E knock-out (ApoE-/-) male mice which received a single dose (2 or 8 Gy) of X-rays to the heart with simultaneous exposure of liver to low doses (no more than 30 and 120 mGy, respectively). Livers were collected for analysis 60 weeks after irradiation and used for morphological, ultrastructural, and biochemical studies. The results show increased damage to mitochondrial ultrastructure and lipid deposition in hepatocytes of irradiated animals as compared to non-irradiated controls. Stronger radiation-related effects were noted in ApoE-/- mice than wild-type animals. In contrast, radiation-related changes in the activity of lysosomal hydrolases, including acid phosphatase, ß-glucuronidase, N-acetyl-ß-D-hexosaminidase, ß-galactosidase, and α-glucosidase, were observed in wild type but not in ApoE-deficient mice, which together with ultrastructural picture suggests a higher activity of autophagy in ApoE-proficient animals. Irradiation caused a reduction of plasma markers of liver damage in wild-type mice, while an increased level of hepatic lipase was observed in plasma of ApoE-deficient mice, which collectively indicates a higher resistance of hepatocytes from ApoE-proficient animals to radiation-mediated damage. In conclusion, liver dysfunctions were observed as late effects of irradiation with an apparent association with malfunction of lipid metabolism.

Multivariable quantitative relation between cell viability and the exposure parameters of 9.33 GHz RF-EMP irradiation.

Qualitative analysis of the influence of a certain exposure parameter is commonly performed in bioelectromagnetic studies. However, since the exposure condition requires the control of multiple parameters, the diverse results caused by different combinations of these parameters requires further quantitative study of the multivariable (exposure parameters)-bioeffect relation to identify the rule describing bioelectromagnetic effects. The present work investigated the relation between cell viability and the three main exposure parameters (electric intensity (Es), pulse duration (τ) and pulse number (N)) of 9.33 GHz radiofrequency electromagnetic field (RF-EMP). Experiments showed that the inhibitory rate of cell viability (ρ) had a proportional relationship with Es and exponential relationship with N; the equation [Formula: see text] is proposed to quantitatively describe the relation between the cell viability and these three exposure parameters. This equation can be used to predict the significance of a 9.33 GHz RF-EMP-induced bioeffect under the conditions Es <106 kV/m, N < 100, and 300 < τ < 750 ns, under which nonthermal bioeffects dominate for 9.33GHz RF-EMP exposure.

Caveolin-1 is involved in DNA damage and repair signaling in X-irradiated Chang liver cells.

Caveolin-1 (Cav-1), as an important structural protein of caveolae, has been proven to be correlated with several signal transduction pathways. Recent studies have shown that Cav-1 may play a critical role in response to DNA damage in irradiated pancreatic cancer cells. However, it is not known whether down-regulation of Cav-1 is required to enhance the damage of other kinds of human cells exposed to X-radiation. In this study, the role of Cav-1 in Chang liver cell line (CHL) exposed to X-radiation was investigated. Cav-1 knockdown cell line (CHL-CAV7) was stably established by the siRNA plasmids transfection, and Cav-1 expression was suppressed by 60%, compared with that of control group (CHL-C) which was transfected with non-targeting plasmids. Cellular survival ability and the expressions of proteins related to DNA damage and repair were examined by colony formation assay and Western blot, respectively. Down-regulation of Cav-1 expression induced a significant decrease of the survival rate in CHL-CAV7 cells exposed to 8 and 10 Gy X-radiation. Compared with CHL-C cells, CHL-CAV7 cells showed increased γH2AX expression, as well as decreased p-ATM, DNA-dependent protein kinase, catalytic subunit (DNA-PKcs) and p53 protein expressions when treated with X-radiation. Meanwhile, the colocalization of Mdm2 and Cav-1 was decreased in CHL-CAV7 cells compared with that in CHL-C cells. These results suggest that the down-regulation of Cav-1 may aggravate DNA damage of CHL cells through reducing the interaction of Cav-1 and Mdm2, which results in the promotion of p53 degradation.

Secretion pathway of liver IGF-1 via JAK2/STAT3 in chick embryo under the monochromatic light.

This study reveals mechanism of monochromatic light on the IGF-1 secretion of chick embryo liver. The chick embryos were incubated and exposed to continuous red, green, blue light or a dark environment. Compared to other light-treated groups, green light increased IGF-1 and melatonin concentrations both in plasma and liver, and Mel1a, Mel1b and Mel1c receptors expressions in liver but decreased p-JAK2, p-STAT3 and ROS in liver. IGF-1 had a positive correlation with melatonin, but a negative relevance with p-JAK2 and p-STAT3. In vitro, the IGF-1 level in the hepatocyte supernatant was enhanced by melatonin with lower p-JAK2/p-STAT3 and ROS levels, which was suppressed by Mel1c antagonist but not Mel1a/Mel1b or Mel1b antagonists. AG490 (JAK/STAT inhibitor) promoted role of melatonin-Mel1c modulated IGF-1 secretion. These results suggest the antioxidant effect of melatonin mediated the green light-enhanced IGF-1 secretion of chick embryo liver through Mel1c receptor to inhibit the JAK2/STAT3 pathway.

Methylene blue toxicity in zebrafish cell line is dependent on light exposure.

Methylene blue (MB) has been widely applied in the clinical area and is currently being used in aquaculture as biocide. Some recent studies have emphasized the importance of understanding the action mechanism and the MB cellular targets. In this sense, zebrafish is considered a relevant model to study the intrinsic pathway of apoptosis as well as the cellular responses involving DNA damage and repair. So, the aim of the present study was to compare MB action mechanisms in a zebrafish cell line, both in the absence (MB alone; dark toxicity) and in the presence of photosynthetically active radiation (MB+PAR; phototoxicity). There was a significant increase of the levels of reactive oxygen and nitrogen species 3 h after MB treatment, whereas this increase was only observed 12 h after treatment with MB+PAR. All treatments with MB resulted in an increase in DNA damage after 3 and 6 h. However, cell death by apoptosis was observed from 6 h after treatment with MB+PAR and 12 h after treatment with MB alone. The expression of genes related to apoptosis was altered after MB and MB+PAR treatment. Therefore, this zebrafish cell line is sensitive to the photodynamic action of MB; MB is able to generate DNA damage and induce apoptosis in this cell line both alone and in the presence of PAR. However, the pathways leading to apoptosis in this model appear to be dependent on the type of MB exposure (in the presence or absence of PAR).

Characterisation of artemisinin-chloroquinoline hybrids for potential metabolic liabilities.

1. Chemotherapy remains the effective way of controlling malaria infections. Many of the treatments have been rendered ineffective as a result of drug resistance by plasmodia species as well as toxicity. Molecular hybridisation is one of the techniques used in the synthesis of new-generation antimalarial techniques. In this paper, we explore some potential metabolic challenges associated with this technique. 2. In vitro metabolic clearance and metabolite identification were performed in cryopreserved hepatocytes. Reaction phenotyping and inhibition studies were conducted in human liver microsomes and recombinant cytochrome P450s (CYPs) 3. Metabolism in hepatocytes was not extensive with less than 25% of the hybrids being metabolised by contributing CYP enzymes. The hybrids were, however, potent inhibitors of CYPs 2C9 2C19 and 3A4. 4. Our data indicated that artemisinin-chloroquinoline hybrid both gained and lost favourable properties from the individual pharmacophoric units from which they were built. This highlights the challenges associated with the molecular hybridisation technique and a need to optimise the chemistry in an effort to maintain good properties while addressing new liabilities that arise.

Influence of Lyophilized Amaranthus retroflexus Extract on Radioresistance of Laboratory Mice after Single X-Ray Exposure.

Radioprotective therapeutic effect of lyophilized extract ofAmaranthus retroflexus on the resistance of the albino laboratory male mice exposed to X-ray radiation at a one-time dose of LD(100/30) is studied. It was established that a 30-day use of a lyophilized extract of the vegetative parts of A. retroflexus at a dose of 50 mg/kg after X-ray exposure increases the survival rate of mice by 80%, enhances the recovery in the radiation period of the number of leukocytes, neutrophils, lymphocytes in the peripheral blood of the animals and the normalization of the intensity of peroxide oxidation of lipids in liver cells. Dose modification factor on the 5th day after irradiation, when using a lyophilized extract, was 1.5 according to the criterion of survival of mice.

Structural and ultrastructural study of rat liver influenced by electromagnetic radiation.

Mobile communication systems are undoubtedly an environmental source of electromagnetic radiation (EMR). There is an increasing concern regarding the interactions of EMR with the humans. The aim of this study was to examine the effects of EMR on Wistar rat liver. Mature rats were exposed to electromagnetic field of frequency 2.45 GHz and mean power density of 2.8 mW/cm2 for 3 h/d for 3 wk. Samples of the liver were obtained 3 h after the last irradiation and processed histologically for light and transmission electron microscopy. Data demonstrated the presence of moderate hyperemia, dilatation of liver sinusoids, and small inflammatory foci in the center of liver lobules. Structure of hepatocytes was not altered and all described changes were classified as moderate. Electron microscopy of hepatocytes revealed vesicles of different sizes and shapes, lipid droplets, and proliferation of smooth endoplasmic reticulum. Occasionally necrotizing hepatocytes were observed. Our observations demonstrate that EMR exposure produced adverse effects on rat liver.

Establishment of a hepatocyte steatosis model using Chang liver cells.

The objective of this study was to explore the experimental conditions for hepatocellular steatosis models of Chang liver cells induced by oleic acid (OA). For that, Chang liver cells were induced by different concentrations of OA for different periods. The MTT assay was used to detect hepatic cell activity, the Oil Red O staining was used to observe intracellular lipid droplets accumulation, and the glycerol phosphate oxidase method was used to detect the triglyceride (TG) content in the Chang liver cell. The hepatocellular steatosis models of Chang liver cell were established successfully by inducing with 0.2 mM OA for 24h. TG content in model cells was 379.98 ± 23.19 mg/g, which is significantly different from control cells (185.03 ± 12.68 mg/g; P < 0.01). These were considered proper conditions for establishing hepatocellular steatosis models of Chang liver cells, producing a reliable model for nonalcoholic fatty liver disease research.

Low frequency magnetic force augments hepatic differentiation of mesenchymal stem cells on a biomagnetic nanofibrous scaffold.

Liver tissue engineering using polymeric nanofibrous scaffold and stem cells holds great promises for treating end-stage liver failures. The aim of this study was to evaluate hepatic trans-differentiation potential of human mesenchymal stem cells (hMSCs) on a biomagnetic electrospun nanofibrous scaffold fabricated from a blend of poly-L-lactide (PLLA), collagen and fibrin-rich blood clot, under the influence of a low frequency magnetic field. The scaffold was characterized for surface properties, biochemical and biomechanical parameters and bio-magnetic behaviour. Cell proliferation assay revealed that the scaffold was suitable for hMSCs adhesion and proliferation. Hepatic trans-differentiation potential of hMSCs was augmented on nanofibrous scaffold in magnetic field exposure group compared to control groups, as evident by strong expression of hepatocyte specific markers, albumin release, urea synthesis and presence of an inducible cytochrome P450 system. Our results conclude that biomagnetic scaffold of PLLA/collagen/blood clot augments hepatic trans-differentiation of hMSCs under magnetic field influence.

Responses to ROS inducer agents in zebrafish cell line: differences between copper and UV-B radiation.

Fish are commonly exposed to environmental pollutants, which in turns could induce an oxidative stress. So, it is important to understand the effects and the responses elicited by these toxicants in fish species, being fish cell lines important tools for this purpose. Thus, the aim of the present study was to compare the effects of copper and UV-B radiation exposure on zebrafish hepatocytes (ZFL lineage) in terms of reactive oxygen species (ROS) levels, sulfhydril groups content and mRNA levels of important genes related to cellular response to toxic agents. Exposure of ZFL cells to UV-B radiation (23.3 mJ/cm(2)) significantly increased levels of intracellular ROS and mRNA of both superoxide dismutase isoforms (sod1 and sod2), three glutathione S-transferase isoforms (gstα, gstµ and gstπ) and a heat shock protein (hsp70). However, no changes in nonprotein sulfhydryl groups (NP-SH) content, as well as in the mRNA levels of genes related to glutathione (GSH) synthesis and recycling, were observed. Contrary to this, copper exposure (20 mg/L) diminished NP-SH content and increased the levels of mRNA of genes related to GSH synthesis (gclc and gs). Moreover, copper exposure increases the mRNA levels of some genes related to antioxidant defenses (gpx and gstπ), biotransformation reactions (cyp1a1) and protein repair (hsp70). In conclusion, these results demonstrated that both toxicants could increase ROS levels in ZFL cell line, but the responses are different, which could be related to activation of different signaling pathways.

[Effect of low-intensity 900 MHz frequency electromagnetic radiation on rat liver and blood serum enzyme activities].

The comparative analysis of the rat liver and blood serum creatine kinase, alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase and purine nucleoside phosphorylase post-radiation activity levels after a total two-hour long single and fractional exposure of the animals to low-intensity 900 MHz frequency electromagnetic field showed that the most sensitive enzymes to the both schedules of radiation are the liver creatine kinase, as well as the blood serum creatine kinase and alkaline phosphatase. According to the comparative analysis of the dynamics of changes in the activity level of the liver and blood serum creatine kinase, alanine aminotransferase, aspartate aminotransferase and purine nucleoside phosphorylase, both single and fractional radiation schedules do not affect the permeability of a hepatocyte cell membrane, but rather cause changes in their energetic metabolism. The correlation analysis of the post-radiation activity level changes of the investigated enzymes did not reveal a clear relationship between them. The dynamics of post-radiation changes in the activity of investigated enzyme levels following a single and short-term fractional schedules of radiation did not differ essentially.

Developing an RNA Signature for Radiation Injury Using a Human Liver-on-a-Chip Model.

Radiation exposure in a therapeutic setting or during a mass casualty event requires improved medical triaging, where the time to delivery and quantity of medical countermeasures are critical to survival. Radiation-induced liver injury (RILI) and fibrosis can lead to death, but clinical symptoms manifest late in disease pathogenesis and there is no simple diagnostic test to determine RILI. Because animal models do not completely recapitulate clinical symptoms, we used a human liver-on-a-chip model to identify biomarkers of RILI. The goals of this study were: 1. to establish a microfluidic liver-on-a-chip device as a physiologically relevant model for studying radiation-induced tissue damage; and 2. to determine acute changes in RNA expression and biological pathway regulation that identify potential biomarkers and mechanisms of RILI. To model functional human liver tissue, we used the Emulate organ-on-a-chip system to establish a co-culture of human liver sinusoidal endothelial cells (LSECs) and hepatocytes. The chips were subject to 0 Gy (sham), 1 Gy, 4 Gy, or 10 Gy irradiation and cells were collected at 6 h, 24 h, or 7 days postirradiation for RNA isolation. To identify significant expression changes in messenger RNA (mRNA) and long non-coding RNA (lncRNA), we performed RNA sequencing (RNASeq) to conduct whole transcriptome analysis. We found distinct differences in expression patterns by time, dose, and cell type, with higher doses of radiation resulting in the most pronounced expression changes, as anticipated. Ingenuity Pathway Analysis indicated significant inhibition of the cell viability pathway 24 h after 10 Gy exposure in LSECs but activation of this pathway in hepatocytes, highlighting differences between cell types despite receiving the same radiation dose. Overall, hepatocytes showed fewer gene expression changes in response to radiation, with only 3 statistically significant differentially expressed genes at 7 days: APOBEC3H, PTCHD4, and GDNF. We further highlight lncRNA of interest including DINO and PURPL in hepatocytes and TMPO-AS1 and PRC-AS1 in LSECs, identifying potential biomarkers of RILI. We demonstrated the potential utility of a human liver-on-a-chip model with primary cells to model organ-specific radiation injury, establishing a model for radiation medical countermeasure development and further biomarker validation. Furthermore, we identified biomarkers that differentiate radiation dose and defined cell-specific targets for potential radiation mitigation therapies.

Construction of liver tissue in vivo with preparative partial hepatic irradiation and growth stimulus: investigations of less invasive techniques and progenitor cells.

BACKGROUND: The selective proliferation of transplanted hepatocytes with a growth stimulus, such as partial hepatectomy or hepatocyte growth factor, concomitant with hepatic irradiation (HIR), which can suppress proliferation of host hepatocytes, has been reported. We have conducted experiments that focused on less invasive and clinically applicable techniques and progenitor cells. MATERIALS AND METHODS: First, dipeptidyl-peptidase IV-F344 or jaundiced Gunn rats underwent partial HIR (only 30% of whole liver) and portal vein branch ligation (PVBL) of one lobe, followed by intrasplenic hepatocyte transplantation at 1 × 10(7). Second, after partial HIR and PVBL, two types of progenitor cells were transplanted (i.e., small hepatocytes (SHs) or adipose-derived mesenchymal stem cells. RESULTS: Sixteen weeks after transplantation, the donor cells constituted > 70% of the hepatocytes of the irradiated lobe, showing connexin 32, phosphoenolpyruvate carboxykinase-1, and glycogen storage. Moreover, the serum bilirubin level had decreased significantly in the jaundiced Gunn rats and remained at this level throughout the 24 wk experimental period. The SHs grew more quickly than the hepatocytes. After 8 wk, around 40% of the host hepatocytes had been replaced by transplanted SHs. Although the donor adipose-derived mesenchymal cells were engrafted after 8 wk, their proliferation was not observed. CONCLUSIONS: HIR, combined with PVBL, can be given to a selective liver lobe and is a less-invasive but effective method for proliferation of transplanted hepatocytes. Even a smaller number of SHs can construct liver tissue with their prevailing proliferative ability.

Ginkgo biloba and Angelica archangelica bring back an impartial hepatic apoptotic to anti-apoptotic protein ratio after exposure to technetium 99mTc.

PURPOSE: The aim of this study was to study the effect of ionizing radiation on apoptosis-related protein concentrations as well as the radio-protective role of Ginkgo biloba and Angelica archangelica. The experiments were performed on 68 adult Wistar rats weighing 175 g (±10 g). Animals were subdivided into control group in which the animals received neither the protector nor the isotopes. The second group represents the animals that received 1 mCi of (99m)Tc only. The third group represents the animals that received A. archangelica for 7 days. The fourth group represents the animals that received G. biloba for 7 days. The fifth group represents the animals that received 1 mCi of (99m)Tc once after receiving A. archangelica for 7 days. The sixth group represents the animals that received mCi of (99m)Tc once after receiving G. biloba for 7 days. Radiation was administered as intravenous injection by 1 mCi of (99m)Tc with the legend methoxyisobutylisonitrile for 24 h. The concentration of p53, Bcl2 and malondialdehyde in liver as well as histopathological examination of liver cells were carried out. Results showed that apoptotic to anti-apoptotic protein ratio significantly (p < 0.05) returned to its normal ratio when radioisotopic injection was administered after the protection period for a week by both A. archangelica and G. biloba in a dose based on the animal body weight. Electron microscope photographing supported this finding. CONCLUSION: It was concluded that both antioxidants can be used as radio-protective agents in cases of ionizing radiation exposure.