The regulatory effects of pomiferin dietary on nickel-induced hepatic injury in Sprague-Dawley rats; action mechanisms and signaling pathways.

The new technological applications of nickel (Ni) raise concerns over its harmful effects on the environment and human health. Pomiferin isolated from Osage orange is evaluated in in vitro and in vivo laboratory bioassays. This study focused the effects of pomiferin on Ni-caused hepatic injury and its underlying mechanisms. With this aim, Sprague-Dawley rats received 10 mg/kg nickel chloride (NiCl2) for 7 d by intraperitoneal injections. Pomiferin was given orally once a day at different doses (75, 150, and 300 mg/kg) for 20 d after exposure to NiCl2. Animals were anesthetized and livers were carefully collected to evaluate oxidative stress, inflammation, vascular injury, and hepatic function. Also, immunofluorescence analysis of apoptosis and DNA damage was performed on rat hepatic tissues. NiCl2 increased MDA production while reducing SOD, CAT, and GPx activity. NiCl2 induced the production of inflammatory cytokines and also platelet activation in hepatic tissue. Moreover, there were significant increases in AST, ALT, and LDH levels. NiCl2 also caused significant pathological changes in hepatic. Additionally, it remarkably induced up-regulations of apoptotic marker and 8-OHdG expressions by immunofluorescence labeling in liver cells. Whereas, pomiferin significantly attenuated lipid peroxidation and increased antioxidant defense system in liver. Also, the use of pomiferin prevented deregulated inflammatory process by signaling pathways nuclear factor kappa B (NFκB)/COX-2/TNF-α/IL-1ß/IL-6. In addition, pomiferin diminished histopathologic evidence of hepatic toxicity and significantly lower expressions of caspase 3 and 8-OHdG were observed in liver cells. Pomiferin seems to counteract the deleterious effects of NiCl2 on hepatic tissue through different cellular and signaling mechanisms.

NiCl₂ induced the production of inflammatory cytokines and also platelet activation in hepatic tissue.NiCl₂ increased MDA production while reducing SOD, CAT, and GPx activity.NiCl₂ induced the production of inflammatory cytokines and also platelet activation in hepatic tissue.NiCl₂ caused significant pathological changes in the liver and also up-regulation of apoptotic marker and 8-OHdG expressions by immunofluorescence staining.Pomiferin attenuated lipid peroxidation and increased antioxidant defense system in liver.The use of pomiferin prevented deregulated inflammatory process by signaling pathways nuclear factor kappa B (NFκB)/COX-2/TNF-α/IL-1ß/IL-6.Pomiferin diminished histopathologic evidence of hepatic toxicity and significantly lower expressions of caspase 3 and 8-OHdG were observed in liver cells.Pomiferin seems to counteract the deleterious effects of NiCl₂ on hepatic tissue through different cellular and signaling mechanisms and thus can be used as a therapeutic practice against metal toxicity.

Hispidulin exerts a protective effect against oleic acid induced-ARDS in the rat via inhibition of ACE activity and MAPK pathway.

This study investigates the protective role of Hispidulin on acute respiratory distress syndrome (ARDS) in rats. Rats were divided into three groups: control, ARDS, ARDS+ Hispidulin. The ARDS models were established by injecting rats with oleic acid. Hispidulin (100 mg/kg) was injected i.p. an hour before ARDS. Myeloperoxidase (MPO), Interleukin-8 (IL-8), Mitogen-activated protein kinases (MAPK), Lipid Peroxidation (LPO), Superoxide Dismutase (SOD), Glutathione (GSH), and Angiotensin-converting enzyme (ACE) were determined by ELISA. Tumor necrosis factor-alpha (TNF-α) expression was described by RT-qPCR. Caspase-3 immunostaining was performed to evaluate apoptosis. Compared with the model group, a significant decrease was observed in the MPO, IL-8, MAPK, ACE, LPO levels, and TNF-α expression in the ARDS+ Hispidulin group. Moreover, reduced caspase-3 immunoreactivity and activity of ACE were detected in the Hispidulin+ARDS group. The protective effect of Hispidulin treatment may act through inhibition of the ACE activity and then regulation of inflammatory cytokine level and alteration of apoptosis.

In Vitro Transcriptome Analysis of Cobalt Boride Nanoparticles on Human Pulmonary Alveolar Cells.

Nanobiotechnology influences many different areas, including the medical, food, energy, clothing, and cosmetics industries. Considering the wide usage of nanomaterials, it is necessary to investigate the toxicity potentials of specific nanosized molecules. Boron-containing nanoparticles (NPs) are attracting much interest from scientists due to their unique physicochemical properties. However, there is limited information concerning the toxicity of boron-containing NPs, including cobalt boride (Co2B) NPs. Therefore, in this study, Co2B NPs were characterized using X-ray crystallography (XRD), transmission electron microscope (TEM), scanning electron microscope (SEM), and energy-dispersive X-ray spectroscopy (EDX) techniques. Then, we performed 3-(4,5-dimethyl-thiazol-2-yl) 2,5-diphenyltetrazolium bromide (MTT), lactate dehydrogenase (LDH) release, and neutral red (NR) assays for assessing cell viability against Co2B NP exposure on cultured human pulmonary alveolar epithelial cells (HPAEpiC). In addition, whole-genome microarray analysis was carried out to reveal the global gene expression differentiation of HPAEpiC cells after Co2B NP application. The cell viability tests unveiled an IC50 value for Co2B NPs of 310.353 mg/L. The results of our microarray analysis displayed 719 gene expression differentiations (FC ≥ 2) among the analyzed 40,000 genes. The performed visualization and integrated discovery (DAVID) analysis revealed that there were interactions between various gene pathways and administration of the NPs. Based on gene ontology biological processes analysis, we found that the P53 signaling pathway, cell cycle, and cancer-affecting genes were mostly affected by the Co2B NPs. In conclusion, we suggested that Co2B NPs would be a safe and effective nanomolecule for industrial applications, particularly for medical purposes.

Boron Compounds Exhibit Protective Effects against Aluminum-Induced Neurotoxicity and Genotoxicity: In Vitro and In Vivo Study.

Genetic, neuropathological and biochemical investigations have revealed meaningful relationships between aluminum (Al) exposure and neurotoxic and hematotoxic damage. Hence, intensive efforts are being made to minimize the harmful effects of Al. Moreover, boron compounds are used in a broad mix of industries, from cosmetics and pharmaceuticals to agriculture. They affect critical biological functions in cellular events and enzymatic reactions, as well as endocrinal and mineral metabolisms. There are limited dose-related data about boric acid (BA) and other boron compounds, including colemanite (Col), ulexite (UX) and borax (BX), which have commercial prominence. In this study, we evaluate boron compounds' genetic, cytological, biochemical and pathological effects against aluminum chloride (AlCl3)-induced hematotoxicity and neurotoxicity on different cell and animal model systems. First, we perform genotoxicity studies on in vivo rat bone marrow cells and peripheric human blood cultures. To analyze DNA and chromosome damage, we use single cell gel electrophoresis (SCGE or comet assay) and micronucleus (MN) and chromosome aberration (CA) assays. The nuclear division index (NDI) is used to monitor cytostasis. Second, we examine the biochemical parameters (superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-Px), malondialdehyde (MDA), total antioxidant capacity (TAC) and total oxidative status (TOS)) to determine oxidative changes in blood and brain. Next, we assess the histopathological alterations by using light and electron microscopes. Our results show that Al increases oxidative stress and genetic damage in blood and brain in vivo and in vitro studies. Al also led to severe histopathological and ultrastructural alterations in the brain. However, the boron compounds alone did not cause adverse changes based on the above-studied parameters. Moreover, these compounds exhibit different levels of beneficial effects by removing the harmful impact of Al. The antioxidant, antigenotoxic and cytoprotective effects of boron compounds against Al-induced damage indicate that boron may have a high potential for use in medical purposes in humans. In conclusion, our analysis suggests that boron compounds (especially BA, BX and UX) can be administered to subjects to prevent neurodegenerative and hematological disorders at determined doses.

Effects of boric acid on ovarian tissue damage caused by experimental ischemia/reperfusion.

We investigated the role of boric acid (BA) in ovarian tissue damage caused by ischemia/reperfusion (I/R) in the rat. We established four groups of seven adult female rats: untreated control; ovarian I/R; 15 mg/kg BA; I/R + 15 mg/kg BA. Ovarian levels of lipid peroxidase (LPO), myeloperoxidase (MPO), glutathione (GSH), catalase (CAT), superoxide dismutase (SOD) and interleukin-6 (IL-6) were measured biochemically. Ovaries were evaluated for histopathology and investigated using immunohistochemistry. We detected greater LPO activity and less CAT, SOD and GSH levels in the I/R groups compared to the control group. LPO and MPO levels in ovarian samples for the I/R goup were increased significantly compared to untreated controls. The levels of LPO and MPO in ovarian tissue for the I/R + BA group were not significantly different from controls. SOD and GSH activity in ovarian tissue was increased significantly compared to controls. We found degenerated parenchymal cells, hemorrhage, necrotic parenchyma cells and congestion in the I/R groups. Expression of 8-OHdG was greater in the I/R group than in controls. Although immunostained cells were dense in the ovarian tissue in the I/R group, the number of immunostained cells was decreased by application of BA to the I/R group. BA exhibits a protective effect on ovarian tissue against I/R damage in the rat.

Molecular Genetics and Cytotoxic Responses to Titanium Diboride and Zinc Borate Nanoparticles on Cultured Human Primary Alveolar Epithelial Cells.

Titanium diboride (TiB2) and zinc borate (Zn3BO6) have been utilized in wide spectrum industrial areas because of their favorable properties such as a high melting point, good wear resistance, high hardness and thermal conductivity. On the other hand, the biomedical potentials of TiB2 and Zn3BO6 are still unknown because there is no comprehensive analysis that uncovers their biocompatibility features. Thus, the toxicogenomic properties of TiB2 and Zn3BO6 nanoparticles (NPs) were investigated on human primary alveolar epithelial cell cultures (HPAEpiC) by using different cell viability assays and microarray analyses. Protein-Protein Interaction Networks Functional Enrichment Analysis (STRING) was used to associate differentially expressed gene probes. According to the results, up to 10 mg/L concentration of TiB2 and Zn3BO6 NPs application did not stimulate a cytotoxic effect on the HPAEpiC cell cultures. Microarray analysis revealed that TiB2 NPs exposure enhances cellular adhesion molecules, proteases and carrier protein expression. Furthermore, Zn3BO6 NPs caused differential gene expressions in the cell cycle, cell division and extracellular matrix regulators. Finally, STRING analyses put forth that inflammation, cell regeneration and tissue repair-related gene interactions were affected by TiB2 NPs application. Zn3BO6 NPs exposure significantly altered inflammation, lipid metabolism and infection response activator-related gene interactions. These investigations illustrated that TiB2 and Zn3BO6 NPs exposure may affect different aspects of cellular machineries such as immunogenic responses, tissue regeneration and cell survival. Thus, these types of cellular mechanisms should be taken into account before the use of the related NPs in further biomedical applications.

Oxidative stress and cyto-genotoxicity induced by poly-d-glucosamine in human blood cells in vitro.

Poly-N-acetyl-d-glucosamine (CH; chitin) is the main component of the insect skeleton, fungal cell wall, and many crustaceans, including crab and shrimp. CH is the most abundant in nature after cellulose, and it has a complex and hardly soluble structure. Poly-d-glucosamine (CHO; chitosan) is a soluble derivative of CH produced by deacetylation used in many fields, including human health. This study carried out the cytotoxic, genotoxic, and oxidative effects of CHO on human whole blood (hWB) and lymphocytes (LYMs) in dose ranges 6.25-2000 µg/mL, in vitro. Total antioxidant capacity (TAC) and total oxidant status (TOS) analyzes were performed on plasma to appreciate oxidative stress. 3-(4,5-Dimethylthiazol-2-yl)-2,5 diphenyltetrazolium bromide (MTT) and lactate dehydrogenase (LDH) assays were applied to understand the cytotoxicity. Chromosomal aberration (CA) and micronucleus (MN) methods were practiced to evaluate genotoxicity. 6.25-150 µg/mL doses increased TAC and decreased TOS. A decreasing and increasing curve from 200 to 2000 µg/mL on TAC and TOS values were determined, respectively. 0-250 µg/mL doses did not provide any cytotoxic data. However, 500-2000 µg/mL doses showed increasing cytotoxicity and genotoxicity. The study results showed that CHO does not pose a toxic risk to human health at low doses but may pose a threat at high doses.

The effect of lithium tetraborate as a novel cardioprotective agent after renal ischemia-reperfusion injury

Abstract Epidemiological studies suggest that acute kidney injury has certain effect on myocardial function. In this study, for the first time, we tested a boron compound namely lithium tetraborate an act as an anti-oxidant and anti-inflammatory agent in ischemia-reperfusion injury. For this, we employed an in vivo rat model with kidney ischemia reperfusion injury to evaluate cardiac injury to clarify the mechanisms of lithium tetraborate. The evaluation of cardiac injury through kidney artery occlusion and reperfusion rat model indicated that lithium tetraborate could (1) reduce oxidative stress-induced endothelial dysfunction; (2) attenuate the inflammatory response of cardiac cells; and (3) alleviate the apoptosis and necrosis of myocytes. In summary, lithium tetraborate demonstrates significant therapeutic properties that contribute to the amelioration of cardiac damage, and it could be a promising candidate for future applications in myocardial dysfunction.

Inula graveolens induces selective cytotoxicity in glioblastoma and chronic leukemia cells.

OBJECTIVE: Crude oil extracts, components of extracts, and ethanolic extracts of Inula graveolens possess various pharmacological activities on various cancer cells including antioxidative and antiproliferative effects. Aqueous extract of this species has not been investigated on the liquid malignancies and solid tumors with a high incidence of treatment refractoriness and poor survival outcomes such as glioblastoma and leukemia. Hence, the present study aimed to evaluate the cytotoxic efficiency of I. graveolens aqueous extracts on human glioblastoma multiforme and chronic myelogenous leukemia cell lines in comparison to non-cancerous primary rat cerebral cortex and human peripheral blood mononuclear cells. METHODS: The cells were treated with the extracts of I. graveolens (125-1000 µg/mL) for 48 h, the cellular viability was identified using 3'-(4,5dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide assay, and lactate dehydrogenase release was measured to determine the cytotoxic potential. Total oxidant status and apurinic/apyrimidinic endodeoxyribonuclease 1 assays were used to determine the oxidative status of cells and DNA damage, respectively. RESULTS: I. graveolens showed selective cytotoxicity toward human glioblastoma multiforme and chronic myelogenous leukemia cell lines and exhibited a higher antiproliferative effect against cancer cells in comparison to non-cancerous cells. Moreover, it significantly reduced the apurinic/apyrimidinic endodeoxyribonuclease 1 levels on both cancer cell lines as compared with their control cells without changing the levels of an oxidative stress marker. CONCLUSION: The extracts of I. graveolens have anti-cancer potential on human glioblastoma multiforme and chronic myelogenous leukemia cell lines without causing oxidative stress.

The cytotoxic and apoptotic effects of beta-blockers with different selectivity on cancerous and healthy lung cell lines.

ß-blockers having specific affinities to ß-adrenergic receptors are routinely used to treat cardiovascular problems. Additionally, it has been demonstrated that these drugs can be effective in treating apoptosis-related diseases. The current study was conducted to investigate the cytotoxic and apoptotic effects of ß-1 selective esmolol, ß-2 selective ICI-118,551, and non-selective nadolol blockers on the cancerous and healthy lung cells. MTT test was used to evaluate cytotoxicity. Apoptotic actions were examined by using Annexin V-FITC/PI assay, JC-1 staining, ROS test, and the determination of the caspase-4 and -9, Bcl-2, Bax, Bax/Bcl-2, and JNK levels. Although the MRC-5 showed greater resistance than A549 cells, the ß-blockers at 150-250 µM exhibited different levels of cytotoxic effect on both lung cell lines. Esmolol was found to be the most ineffective blocker and the increases in Bcl-2 protein levels were appeared to be effective in resistance to this drug. The increases in reactive oxygen species (ROS) together with the increase in caspase-4 and Bax protein levels have been shown to play a role in ICI-118,551 induced lung cell death. Nadolol was the most effective blocker increasing the total apoptotic cell population in both lung cells, which was based on both mitochondrial and endoplasmic reticulum stress. When the selectivities of the ß-blockers are considered, it seems that ß-2 specific antagonism predominantly mediated the death of lung cells, and the overwhelming factors causing apoptosis mainly varied depending on the selectivity of the blockers.

Ameliorative effect of umbelliferone in remote organ injury induced by renal ischemia-reperfusion in rats.

We evaluated the ameliorative role of umbelliferone in kidney, heart, and lung damage induced by renal ischemia/reperfusion (I/R) injury in rats. Umbelliferone was given orally to rats 60 min before ischemia. Ischemia was induced for 50 min and then reperfusion for 3 hr. The antioxidant enzymes, myeloperoxidase (MPO) activity, malondialdehyde (MDA) content, and cytokine levels in the kidney, heart, and lung were measured by ELISA. Moreover, histopathological changes were monitored. Renal I/R-induced oxidative stress in the organs by decreasing antioxidant enzymes. However, umbelliferone pretreatment enhanced superoxide dismutase (SOD) and glutathione (GSH), levels, reduced MDA and MPO levels. Renal I/R increased in tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6) levels, and histopathological changes but these effects were inhibited with umbelliferone pretreatment. Furthermore, umbelliferone increased in nitric oxide synthase (eNOS) level under ischemia conditions. Our results indicated that pretreatment of umbelliferone-ameliorated damages in remote organ induced by renal I/R through suppressing oxidative stress and modulating inflammatory responses. PRACTICAL APPLICATIONS: kidney, heart, and lung damages induced by renal I/R in rats was alleviated by umbelliferone. The oral treatment of umbelliferone markedly reversed the oxidative stress, inflammation, and histopathological changes by increasing in the levels of SOD, GSH, and eNOS, decreasing in the levels of MDA, MPO, TNF-α, and IL-6 in distant organ injury induced by renal I/R. This study firstly revealed that umbelliferone has potent antioxidant and anti-inflammatory activity in the remote organ damages caused by renal I/R. Consequently, umbelliferone may be an alternative therapeutic agent for treating renal I/R-induced damages.

Safety Assessments of Nickel Boride Nanoparticles on the Human Pulmonary Alveolar Cells by Using Cell Viability and Gene Expression Analyses.

Nickel boride is generally used in the steel industry as a melting accelerator due to its feature of creating a protective and stable attribute at high temperatures. It is also used to improve the hardenability of the steel with boron addition in the production. Thus, safety studies and biocompatibility analysis of nickel boride should be performed comprehensively to understand the limitations of use in various areas. In the present study, nickel boride nanoparticles (Ni2B NPs) were synthesized by a single-step method and molecule characterizations were performed via the use of X-ray diffraction analysis (XRD), transmission electron microscopy (TEM), scanning electron microscopy (SEM), and energy dispersive X-ray (EDX) analyses. Cytotoxicity properties of Ni2B NPs were identified on human pulmonary alveolar epithelial cells (HPAEpiC) by using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), neutral red (NR), and lactate dehydrogenase (LDH) assays. Illumina human ht-12 v4.0 whole-genome microarray analysis was conducted to investigate NiB2 NPs effects on gene expression regulations of HPAEpiC cells. The database for annotation, visualization, and integrated discovery (DAVID) analysis was performed to reveal the relationship between Ni2B NP application and cellular pathway alterations. According to cytotoxicity analysis, the IC50 value for Ni2B NP application was found as 81.99 mg/L concentration. Microarray analysis of Ni2B NP application was shown for the first time that 693 gene expression changes (FC ≥ 2) occurred significantly over 40.000 gene probes and Ni2B NPs were observed to affect microtubule regulation, centrosome organization, and phosphoprotein synthesis.

The targets of ß-sitosterol as a novel therapeutic against cardio-renal complications in acute renal ischemia/reperfusion damage.

This research is the first to use ß-sitosterol on myocardial and renal tissues in renal ischemia/reperfusion (IR) damage. Female Wistar rats were randomly divided into three groups: control (sham), renal IR (50 min ischemia - 3 h reperfusion), and renal IR + 150 mg/kg/p.o. ß-sitosterol (the rats were treated with ß-sitosterol orally once 1 h before the IR procedure). ß-Sitosterol pretreatment caused an increase in superoxide dismutase and glutathione activities and a decrease in malondialdehyde levels in the kidney and heart. Moreover, it alleviated histopathological changes and downregulated the levels of tumor necrosis factor-alpha and interleukin-6 and upregulated the levels of endothelial nitric oxide synthase. As conclusion, the potential of ß-sitosterol for renal and cardiac necrosis and apoptosis appears to act by limiting inflammatory response and oxidative stress. Thus, the potential of this compound is noteworthy and may serve as a potential therapeutic in the treatment of acute organ damages due to renal IR.

(1 → 3)-ß-d-glucan enhances the toxicity induced by Bortezomib in rat testis.

We aimed to determine the possible effects of the antioxidant agent (1 â†’ 3)-ß-D-glucan on bortezomib-induced rat testis damage. We used five groups of rats; control, (1 â†’ 3)-ß-D-glucan (75 mg/kg), bortezomib group, bortezomib + (1 â†’ 3)-ß-D-glucan groups (injection of (1 â†’ 3)-ß-D-glucan after bortezomib and sacrificed at 48th or 72nd h). The effects of these substances were assessed by measuring the levels of the antioxidant enzymes and LPO, and by performing immunohistochemical analysis with NF-κB. The histology of testis was evaluated using aniline blue staining. (1 â†’ 3)-ß-D-glucan leads to significant reductions in the levels of antioxidant enzymes and increased levels of LPO in testes. Moreover, it increased the NF-κB immunopositivity significantly in testis, especially in Bortezomib + (1 â†’ 3)-ß-D-glucan group at 48th h. The histological changes were observed in the bortezomib and/or (1 â†’ 3)-ß-D-glucan groups. Our results demonstrated that testis damage caused by the treatment with bortezomib was not eliminated by (1 â†’ 3)-ß-D-glucan and shockingly it increased the damage. PRACTICAL APPLICATIONS: The testis damage caused by the treatment with bortezomib was not eliminated by (1 â†’ 3)-ß-D-glucan and as a result, ß-1,3-(D)-glucan enhanced the toxicity by leading a decrease in the levels of GSH, SOD, and CAT, thus caused an elevation in the immunoreactivity of NF-κB and altered the histopathological changes by enhancing the toxic effects of bortezomib. The findings of the previous studies about the antioxidative activity of (1 â†’ 3)-ß-D-glucan are controversial. So, it is necessary to consider the cytotoxicity of (1 â†’ 3)-ß-D-glucan in testis tissue. Thus, more studies on testis tissue are necessary to confirm that (1 â†’ 3)-ß-D-glucan is safe as an antioxidant.

Gastroprotective effects of oleuropein and thymol on indomethacin-induced gastric ulcer in Sprague-Dawley rats.

Ethnopharmacological studies demonstrated that thymol (Thym) and oleuropein (Ole) have therapeutic potential for gastric ulcers. The molecular mechanism underlying the gastroprotective effects of these compounds have not been elucidated yet especially for their individual and combination use at high dose. Therefore, this study was conducted to explore their gastroprotective mechanisms on indomethacin (Indo)-induced gastric ulcer model. Ole (50,100, 250, and 500 mg/kg) and Thym (50,100, 200, and 500 mg/kg) were orally administered to the rats 10 min before the induction of ulcer with Indo. The combination of 500 mg/kg doses of Ole and Thym were applied. The gastric mucosa was evaluated histopathologically. Moreover, TAC/TOS, tumor necrosis factor-alpha (TNF-α), prostaglandin E2 (PGE2), endothelial nitric oxide synthase (eNOS), and caspase-3 levels were assessed by ELISA and the caspase-3 and TNF-α expressions were quantified by qRT-PCR. Indo-induced histopathological changes while Ole and Thym pretreatment prevented these effects. Unlike the 500 mg/kg dose of Ole treatment, the 500 mg/kg dose of Thym administration enhanced these damages. The decreased TAC, PGE2 levels and increased TOS, eNOS, TNF-α, caspase-3 levels were obtained in Indo group. However, these changes were reversed by Ole and Thym groups except the 500 mg/kg dose of Thym and the combination treatment groups. Similar trends were observed in the caspase-3 and TNF-α expression levels. These results demonstrated that enhanced inflammation, oxidant/antioxidant imbalance, and apoptotic activities were occurred in Indo, 500 mg/kg dose of Thym and the combination treatment groups while not in the other groups. The findings demonstrated the gastroprotective ability of Ole and low doses of Thym in gastric ulcer models.

The propolis and boric acid can be highly suitable, alone/or as a combinatory approach on ovary ischemia-reperfusion injury.

PURPOSE: Ovarian ischemia-reperfusion (IR) damage continues to be a serious infertility problem. The oxidative stress plays central role in the development of IR injuries. Activation of antioxidants decreases IR injuries; however, the efficacy of antioxidant agents remains controversial. Unfortunately, there has been no evidence for medicinal use of boric acid (BA) and propolis (Prop) on ovarian IR injury on rats so far. This study will provide to reveal the potential applications of the Prop and BA in ovarian IR therapy. METHODS: The Sprague-Dawley rats were randomized into five groups: I-control, II-IR, 3 h of ischemia and 3 h of reperfusion, III and IV-a signal dose of oral BA (7 mg/kg) and Prop (100 mg/kg) alone 1 h before induction of IR, V-Prop and BA together 1 h before induction of IR. SOD (superoxide dismutase), CAT (catalase), GSH (glutathione), MPO (myeloperoxidase), MDA (malondialdehyde), and IL-6 (interleukin-6) levels were quantified by ELISA and the TNF-α (tumor necrosis factor-α), 8-OHdG (8-hydroxylo-2'-deoxyguanosin) and Caspase-3 expressions were performed by immunohistochemical analyses. RESULTS: BA and Prop pretreatment significantly reduced MPO, MDA, and IL-6 levels and pathologic score in IR rats, with no effects in control group. These agents used in therapy also decreased TNF-α, 8-OHdG and Caspase-3 protein expressions increased by IR. Furthermore, BA and Prop combination showed significant ameliorative effects on ovary injury caused by IR through acting as an antioxidant, anti-inflammatory and antiapoptotic agent. CONCLUSION: BA and Prop alone and especially in combination could be developed as therapeutic agents against ovary IR injury.

Propolis and Its Combination with Boric Acid Protect Against Ischemia/Reperfusion-Induced Acute Kidney Injury by Inhibiting Oxidative Stress, Inflammation, DNA Damage, and Apoptosis in Rats.

Ischemia reperfusion (I/R) injury which causes kidney dysfunction is one of the most studied diseases directly linked to oxidative stress. In this regard, it is important to protect cells against damage by inducing antioxidant response. Herein, we aimed to evaluate the therapeutic roles and possible mechanisms of propolis and boric acid in kidney I/R injury based on relevant basic research and clinical studies. Sprague-Dawley rats were subjected to 50 min of ischemia followed by 3 h of reperfusion. Animals were randomly divided into a control group (the abdominal wall was just opened and closed), an I/R injury group, the propolis intervention group (200 mg/kg, intragastric administration, 1 h before ischemia), boric acid intervention group (14 mg/kg, intragastric administration 1 h before ischemia), and the propolis + boric acid intervention group (intragastric administration 1 h before ischemia). Kidney function, the antioxidant defensive system, and renal damage were assessed. In addition, the oxidative stress and inflammatory status were estimated in renal tissue. Furthermore, DNA damageand apoptosis were detected by immunohistochemistry. When compared with I/R group, propolis alone and especially propolis + boric acid groups significantly improved functional parameters. While the antioxidant response was increased, renal injury size and apoptosis were significantly decreased in both groups. Also, the MDA and TNF-α levels besides the 8-OHdG formation were downregulated. According to these outcomes, it can be said that especially propolis together with boric acid ameliorates kidney injury caused by I/R through acting as an antioxidant, anti-inflammatory, and antiapoptotic agent. In conclusion, propolis alone and its combination with boric acid could be developed as therapeutic agents against serious renal I/R injuries.

Microarray assisted toxicological investigations of boron carbide nanoparticles on human primary alveolar epithelial cells.

It is important to understand the adverse effects of nanoparticles on human health and to prepare risk reports for widely used nanoscale materials. Synthesis, characterization and cytotoxicity evaluation of B4C nanoparticles were performed on HPAEpiC since, first encounter with nanoparticles would generally happen through lung by inhaling chemicals. B4C nanoparticles were synthesized via chemical vapor deposition techniques and characterized by using transmission electron microscope (TEM), scanning electron microscope (SEM) and X-ray crystallography (XRD). 3-(4,5-dimethyl-thiazol-2-yl) 2,5-diphenyltetrazolium bromide (MTT), lactate dehydrogenase (LDH) and neutral red (NR) tests were used to analyze cell viability and cytotoxicity against nanoparticles exposure. Microarray analysis was used to discover whole genome effects of B4C NPs on gene expressions changes of HPAEpiC cells. Then, the database for annotation, visualization and integrated discovery (DAVID) analysis was performed to understand relationships between gene pathways and nanoparticle exposure. Finally, cytotoxicity analysis revealed that IC20 value for boron carbide (B4C) nanoparticles was 202.525 mg/L. According to microarray analysis 32 genes expression change significantly (FC ≥ 2) over 40,000 genes scanning. The gene pathways analysis showed that boron carbide (B4C) nanoparticles mostly affect amino acid biosynthesis process, TGF-beta signaling pathway and developmental proteins regulation. In conclusion, our results supported for the first time that boron carbide (B4C) nanoparticles could be used as a safe nanomaterial in both pharmacological and medical applications.

Synthesis, characterization and cytotoxicity of boron nitride nanoparticles: emphasis on toxicogenomics.

Nanotechnology is increasingly developing area including more than 700 commercial products such as clothing, food preparation, cosmetics, mechanics, electronics and also health industry. People generally contact with nanoparticles by inhaling from air. Thus, it is becoming important issue to understand harmful effects of nanoparticles on human health and prepare risk reports for common nano-sized materials. In this paper, synthesis, characterization and cytotoxicity evaluation of boron nitride (BN) nanoparticles were performed on human primary alveolar epithelial cells (HPAEpiC) since, main exposure to nanoparticles would generally happen through lung via inhalation. Chemically synthetized BN nanoparticles were characterized by using X-ray crystallography, transmission electron microscope, scanning electron microscope and energy-dispersive X-ray spectroscopy techniques. 3-(4,5-dimethyl-thiazol-2-yl) 2,5-diphenyltetrazolium bromide, neutral red and lactate dehydrogenase release assays were used to analyze cytotoxicity after nanoparticles exposure. Whole genome microarray analysis was used to find out the effects of BN NPs on gene expressions of HPAEpiC cells. Finally, the database for annotation, visualization and integrated discovery analysis was used to reveal relationships between different cellular pathways and nanoparticle exposure. According to cytotoxicity analysis LC20 value for BN nanoparticles was 125.051 mg/L. Microarray results showed that 2159 genes expression change (FC ≥ 2) significantly over 40,000 genes analysis. When the gene pathways were analyzed, it was seemed that BN nanoparticles mostly affect cell cycle, cell-cell interactions, cancer affecting genes and signal transduction. In a conclusion, our results supported for the first time that BN nanoparticles could be used as a safe nanomaterial in both pharmacological and medical applications.