Betaine ameliorates arsenic-induced kidney injury in mice by mitigating oxidative stress-mediated inflammation.

Arsenic, an environmental pollutant and poisonous metalloid, has adverse effects on different body organs, including the kidneys. Betaine is a natural nutrient that has many beneficial health effects. This research was conducted to examine the impact of betaine on nephrotoxicity caused by inorganic arsenic (NaAsO2) in mice. Mice were separated into following groups: control, NaAsO2 (50 ppm), NaAsO2 (50 ppm) + betaine (500 mg/kg), and betaine (500 mg/kg). Mice were received NaAsO2 via drinking water for 8 consecutive weeks and betaine was given to the animals via gavage once daily in the 7th and 8th weeks of the study. Upon completion of the study, the mice were euthanized and samples of serum and kidney were obtained for further evaluations. Administration of NaAsO2 increased the levels of blood urea nitrogen and creatinine in the serum. It enhanced the amounts of renal malondialdehyde and decreased the total thiol levels, as well as the activity of antioxidant enzymes (catalase, superoxide dismutase, and glutathione peroxidase). Furthermore, it enhanced the levels of renal inflammatory indicators (tumor necrosis factor-alpha and nitric oxide). Western blot results exhibited an increase in the protein expression of nuclear factor kappa B (NF-κB), and phosphorylated NF-κB in NaAsO2-treated mice. Histopathological results also confirmed kidney damage caused by NaAsO2. However, treatment with betaine improved NaAsO2-related kidney injuries in mice. The results of this work indicated that betaine can attenuate kidney damage caused by NaAsO2 by inhibiting oxidative stress and inflammation.

Zingerone Alleviates Morphine Tolerance and Dependence in Mice by Reducing Oxidative Stress-Mediated NLRP3 Inflammasome Activation.

Morphine (MPH) is widely used for pain management; however, long-term MPH therapy results in antinociceptive tolerance and physical dependence, limiting its clinical use. Zingerone (ZIN) is a natural phenolic compound with neuroprotective effects. We investigated the effects of single and repeated doses of ZIN on MPH-induced tolerance, dependence, and underlying biochemical mechanisms. After a dose-response experiment, tolerance was developed to MPH (10 mg/kg, i.p.) for seven days. In the single-dose study, ZIN was administered on day seven. In the repeated-dose study, ZIN was administered for seven days. Naloxone (5 mg/kg, i.p., 120 min after MPH) was injected to assess withdrawal signs on day seven. The levels of thiobarbituric acid reactive substances (TBARS), nitric oxide (NO), total thiol (TT), and glutathione peroxidase (GPx) were measured in the prefrontal cortex. The protein levels of interleukin-1 beta (IL-1ß) and NLRP3-ASC-Caspase-1 axis were assessed by ELISA and Western blotting, respectively. Results showed that ZIN (100 mg/kg) had no antinociceptive activity, and subsequent experiments were performed at this dose. Repeated ZIN reversed MPH antinociceptive tolerance, whereas single ZIN did not. Single and repeated ZIN attenuated naloxone-induced jumping. In addition, repeated ZIN significantly inhibited weight loss. Repeated ZIN suppressed the MPH-induced increase in TBARS, NO, IL-1ß, NLRP3, ASC, and Caspase-1. It also inhibited MPH-induced TT and GPx reduction. In contrast, single ZIN had no effect. Findings suggest that ZIN reduces MPH-induced tolerance and dependence by suppressing oxidative stress and NLRP3 inflammasome activation. This study provides a novel therapeutic approach to reduce the side effects of MPH.

Thymoquinone effects on autophagy, apoptosis, and oxidative stress in cisplatin-induced testicular damage in mice.

PURPOSE: In this study, the effect of thymoquinone (TQ) on CP-induced spermatogenesis defects in mice has been investigated. METHODS: Sperm parameters, serum testosterone concentration, histology, Bax/Bcl-2 ratio, and expression of autophagy-related biomarkers have been assessed. Total antioxidant capacity (TAC), total oxidant status (TOS), and oxidative stress index (OSI) in testicular tissue were examined for the evaluation of oxidative stress levels. RESULTS: CP has induced histological changes and significantly increased the Bax/Bcl-2 ratio, decreased testosterone concentration, testicular weight, and sperm quality. CP induced oxidative stress by elevating OSI in the testicular tissue (p < 0.05). Expression of the autophagy-inducer genes (ATG7, ATG5, and Beclin-1) and ratio of LC3B/LC3A proteins were significantly decreased, while mTOR expression was increased in the CP group. TQ pretreatment dose-dependently decreased the Bax/Bcl-2 ratio and mTOR gene expression while increasing the expression of ATG5 and ATG7 genes, LC3B/LC3A ratio, and Beclin-1 proteins. TQ could also dose-dependently reverse the histology, testosterone level, and sperm quality of the CP-intoxicated mice. CONCLUSIONS: These findings show that TQ pretreatment can enhance sperm production by inducing autophagy and reducing apoptosis and oxidative stress in the CP-intoxicated mouse testicles.

Suspended particulate matter promotes epithelial-to-mesenchymal transition in alveolar epithelial cells via TGF-ß1-mediated ROS/IL-8/SMAD3 axis.

Epidemiological evidence presents that dust storms are related to respiratory diseases, such as pulmonary fibrosis (PF). However, the precise underlying mechanisms of SPM-elicited adverse effects still need to be investigated. Epithelial-mesenchymal transition (EMT) process is a characteristic of PF. We discussed whether suspended particulate matter (SPM) is involved in EMT induction via transforming growth factor-ß1 (TGF-ß1). In this study, a detailed elemental analysis (55 elements), particle size, and morphology were determined. To investigate the toxicity of SPM, an MTT test was performed to detect cell viability. Next, A549 cells were exposed to selected concentrations of SPM (20 and 40 µg/mL) for single and repeated exposures. The DCFH-DA assay showed that exposure to SPM could produce reactive oxygen species (ROS). The ELISA assay demonstrated increased levels of interleukin-8 (IL-8) and TGF-ß1 in the supernatant. Western blot was used to detect the expression of proteins associated with EMT and the SMAD3-dependent pathway. Results of western blot demonstrated that E-cadherin was reduced, whereas p-SMAD3, vimentin, and α-smooth muscle actin were elevated. Our findings indicated that SPM triggered EMT by induction of oxidative stress, inflammation, and the TGF-ß1/SMAD3 pathway activation.

The role of l -arginine/NO/cGMP/K ATP channel pathway in the local antinociceptive effect of berberine in the rat formalin test.

Berberine is an isoquinoline alkaloid naturally produced by several types of plants. Berberine has extensive pharmacological effects, such as anti-diabetic, anti-inflammatory, and antioxidant effects. In the current study, we assess the antinociceptive effects of berberine and its association with the l -arginine ( l -Arg)/NO/cGMP/K ATP channel pathway via intraplantar administration in rats. To examine the antinociceptive properties of berberine, the formalin test was conducted. The number of rat paw flinches was counted for an h. l -Arg (precursor of nitric oxide, 3-30 µ g/paw), l -NAME (NO synthase inhibitor, 10 and 100 µ g/paw), methylene blue (guanylyl cyclase inhibitor, 100 and 200 µ g/paw), and glibenclamide (ATP-sensitive potassium channel blocker, 10 and 30 µ g/paw) were locally injected, respectively, into the right hind paws of rats as a pre-treatment before berberine injection to understand how the l -Arg/NO/cGMP/K ATP pathway plays a role in the antinociceptive effect of berberine. The ipsilateral injection of berberine into the right paw (0.1-10 0 µ g/paw) showed a dose-dependent antinociceptive effect in both the first and second phases of the formalin test, almost similar to morphine (25 µ g/paw). Intraplantar injection of l -Arg (30 µg/paw) increased the antinociceptive effect of berberine in the second phase. In addition, injection of l -NAME, methylene blue, and glibenclamide caused a reduction in the antinociceptive effect of berberine throughout the second phase in a dose-dependent manner. However, the antinociceptive effects of berberine in the first phase of the rat formalin test were not affected by this pathway. As a novel local antinociceptive agent, berberine can exert a peripheral antinociceptive effect via the l -Arg/NO/cGMP/K ATP channel pathway.

Dimethyl fumarate attenuates paraquat-induced pulmonary oxidative stress, inflammation and fibrosis in mice.

Paraquat (PQ) is the most important cationic bipyridyl herbicide in the agricultural industry, which is very toxic to humans and animals and causes disruption in many organs, mainly in the lungs. Dimethyl fumarate (DMF) is an immune-modulating drug used in the treatment of multiple sclerosis and psoriasis shows antioxidant, anti-inflammatory, and antifibrotic effects. In this study, the ameliorative effects of DMF (10, 30 and 100 mg/kg, orally) on PQ (30 mg/kg) model of lung damage were evaluated in male mice. DMF was given daily for 7 days and PQ was administrated in the fourth day in a single dose. On the eighth day, the animals were sacrificed, and their lung tissue were removed. The results indicated that DMF can ameliorate PQ-induced the significant increase in lung index, hydroxyproline, as well as TBARS, TGF-ß, NF-κB and decrease in the amount of total thiol, catalase, glutathione peroxidase, superoxide dismutase, Nrf-2, and INF-γ. The histopathological results confirmed indicated findings. The results showed that the protective effect of DMF on PQ-induced toxicity is mediated through antioxidant, anti-inflammatory and antifibrotic activities.

Nephroprotective effect of diosmin against sodium arsenite-induced renal toxicity is mediated via attenuation of oxidative stress and inflammation in mice.

Arsenic compounds, which are used in different industries like pesticide manufacturing, cause severe toxic effects in almost all organs, including the kidneys. Since the primary route of exposure to arsenic is through drinking water, and millions of people worldwide are exposed to unsafe levels of arsenic that can pose a threat to their health, this research was performed to investigate the nephroprotective effects of Diosmin (Dios), a flavonoid found in citrus fruits, against nephrotoxicity induced by sodium arsenite (SA). To induce nephrotoxicity, SA (10 mg/kg, oral gavage) was administered to mice for 30 days. Dios (25, 50, and 100 mg/kg, oral gavage) was given to mice for 30 days prior to SA administration. After the study was completed, animals were euthanized and blood and kidney samples were taken for biochemical and histopathological assessments. Results showed that SA-treated mice significantly increased the blood urea nitrogen and creatinine levels in the serum. This increase was associated with significant kidney tissue damage in SA-treated mice, which was confirmed by histopathological studies. Furthermore, SA enhanced the amounts of renal thiobarbituric acid reactive substances and decreased total thiol reserves, as well as the activity of antioxidant enzymes such as catalase, superoxide dismutase, and glutathione peroxidase. Also, in the SA-exposed group, an increase in the levels of kidney inflammatory biomarkers, including nitric oxide and tumor necrosis factor-alpha was observed. The western blot analysis indicated an elevation in the protein expression of kidney injury molecule-1 and nuclear factor-kappa B in SA-treated mice. However, pretreatment with Dios ameliorated the SA-related renal damage in mice. Our findings suggest that Dios can protect the kidneys against the nephrotoxic effects of SA by its antioxidant and anti-inflammatory characteristics.

Citicoline ameliorates arsenic-induced hepatotoxicity and diabetes in mice by overexpression of VAMP2, PPAR-γ, As3MT, and SIRT3.

The use of arsenic in arsenic-based pesticides has been common in many countries in the past and today. There is considerable evidence linking arsenic exposure to hepatotoxicity and diabetes. Destructive phenomena such as hepatic oxidative stress and inflammation can interfere with glucose uptake and insulin function. In the present study, the antioxidant, anti-inflammatory, and molecular mechanism of citicoline against sodium arsenite-induced hepatotoxicity and glucose intolerance were investigated in mice. Citicoline improved glucose tolerance impaired by sodium arsenite. Citicoline increased the hepatic activity of catalase, superoxide dismutase, and glutathione peroxidase enzymes. Moreover, we found that citicoline prevents an increase in the levels of thiobarbituric acid reactive substances. Citicoline reduced levels of caspase 3, tumor necrosis factor-alpha, and interleukin 6 in sodium arsenite intoxicated groups. It was shown that citicoline increased the expression of arsenite methyltransferase, vesicle-associated membrane protein 2, peroxisome proliferator-activated receptor gamma, and sirtuin 3 to combat sodium arsenite toxicity. Citicoline reduced glucose intolerance, which was disrupted by sodium arsenite, by affecting the pancreatic and extra-pancreatic pathways involved in insulin production, secretion, and action. Based on our results, citicoline can be considered a modulating agent against arsenic-induced hepatotoxicity and hyperglycemia. Considering the relationship between arsenic exposure and the occurrence of side effects such as liver toxicity and diabetes, it is necessary to monitor and awareness of arsenic residues from sources such as drinking water.

ROS-Mediated Antitumor Activity, Apoptosis, and Molecular Docking Studies of Platinum(II) Coordination Complexes Bearing 2-(Diphenylphosphino)pyridine Ligands.

Platinum-based drugs have been widely used in cancer treatment. However, their severe side effects have limited their use. So, researchers have been striving to find compounds with fewer side effects and greater efficacy, to overcome these drawbacks. Here, the cytotoxicity of platinum(II) complexes containing 2-(diphenylphosphino)pyridine ligands have been studied on human lung (A549), ovarian (SKOV3), breast (MCF-7) cancer, and normal breast (MCF-10A) cell lines. The most potent compound exhibits a marked cell growth-inhibitory effect against ovarian and lung cancer cells with IC50 values of 9.41 and 5.58 µM, respectively, which were significantly better than that observed for cisplatin (19.02, and 8.64 µM). Additionally, all complexes achieved significantly lower cytotoxicity towards MCF-10A. To investigate the interaction of complexes with DNA, an electrophoresis mobility shift assay was conducted, which indicated that complexes bind to DNA and affect its electrophoretic mobility. An analysis of apoptosis in A549 cells supported the conclusion that they inhibits cell proliferation via induction of apoptosis in a concentration-dependent manner. Molecular docking was also used to investigate the interactions of compounds with different DNA structures. These compounds have the ability to be a suitable pharmaceutical compound with further investigations in the field of cancer research.

Swimming training combined with chitosan supplementation reduces the development of obesity and oxidative stress in high-fat diet-fed mice.

Obesity is often introduced as one of the metabolic disorders caused by imbalance between energy consumption and metabolisable energy intake. Experts in the field considered obesity as one of the robust risk factors for the lifestyle-associated diseases. The present research examined interventional effects of marine chitosan (CS), swimming training (ST) and combination of CS and ST (CS + ST) in the mice fed with high-fat diets (HFD). In this study, sample size was considered more than three in groups. Forty mice were randomly divided into five groups (n 8 per group) including control group (received the standard diet), HFD group (received high-fat food with 20 % fat), HFD + CS group (treated with high-fat food with 5 % CS), HFD + ST group (treated with HFD and ST) and HFD + CS + ST group (treated with high-fat food with 5 % CS and ST). After 8 weeks, the blood glucose, oxidative stress (OS) and lipid profile were measured. The results showed that CS + ST group has more effects in the control of body weight with the increased concentration of HDL-cholesterol, OS inhibition via enhancing the body antioxidant capacity in comparison with the ST or CS alone in HFD-fed mice. Moreover, lipid profile was improved in CS + ST-treated mice compared with HFD-treated mice, and OS inhibition correlated with the greater activities of the antioxidant enzyme enhances the lipid oxidation, cholesterol and fatty acid homoeostasis. The results suggested that a dietary intervention with a combined ST and CS can be a feasible supplementary for human prevention of obesity.

The protective effect of herniarin on genotoxicity and apoptosis induced by cisplatin in bone marrow cells of rats.

Herniarin is a member of simple coumarins, which are a group of common secondary metabolites in plants. The aim of the present study was to investigate the effects of herniarin on genotoxicity and apoptosis induced by cisplatin in rat bone marrow cells. The experimental rats were treated with four different doses of herniarin (50, 100, 200, and 400 mg/kg.) for seven consecutive days. The cisplatin (5 mg/kg, i.p.) was injected into mice 1 h after the last oral herniarin administration on the seventh day. The protective effects of herniarin were investigated by hematological test, flow cytometry, micronucleus assay, and reactive oxygen species (ROS) level analysis. Herniarin caused a marked reduction in the frequencies of micronucleated polychromatic erythrocytes (MnPCEs) and micronucleated normochromatic erythrocytes (MnNCEs) 24 h after exposure to cisplatin at doses of 200 and 400 mg/kg. Furthermore, herniarin significantly increased the levels of both red and white blood cells in peripheral blood. Treatment of rats with herniarin before cisplatin, significantly decreased the percentage of apoptotic and necrotic cells and the ROS level in bone marrow cells. This study indicated that herniarin can be introduced as a new chemoprotective agent against cisplatin-induced genotoxicity in the future.

The combined effect of dichloroacetate and 3-bromopyruvate on glucose metabolism in colorectal cancer cell line, HT-29; the mitochondrial pathway apoptosis.

BACKGROUND: 5-Fluorouracil (5-FU) is regarded as the first line treatment for colorectal cancer; however, its effectiveness is limited by drug resistance. The ultimate goal of cancer therapy is induction of cancer cell death to achieve an effective outcome with minimal side effects. The present work aimed to assess the anti-cancer activities of mitocans which can be considered as an effective anticancer drug due to high specificity in targeting cancer cells. METHODS: MTT (3-4,5-dimethylthiazol-2-yl-2,5-diphenyltetrazolium bromide) assay was performed to determine the effects of our mitocans on cell viability and cell death. Apoptosis and necrosis, caspase 3 activity, mitochondrial membrane potential and ROS production in HT29 cell lines were analyzed by ApopNexin™ FITC/PI Kit, Caspase- 3 Assay Kit, MitoTracker Green and DCFH-DA, respectively. Moreover, quantitative real-time polymerase chain reaction (qRT-PCR) was performed to detect the expression level of pro-apoptotic (Bax) and anti-apoptotic (Bcl-2) genes in HT29 cell lines. RESULTS: Treatment with mitocans (3Br-P + DCA) inhibited the growth of HT29. Moreover, 3Br-P + DCA significantly induced apoptosis and necrosis, activation of caspase 3 activity, depolarize the mitochondrial membrane potential, and ROS production. At a molecular level, 3Br-P + DCA treatment remarkably down-regulated the expression of Bcl-2, while up-regulated the expression of Bax. CONCLUSION: Mitocans, in particular the combined drug, 3Br-P + DCA, could be regarded and more evaluated as a safe and effective compound for CRC treatment. Targeting hexokinase and pyruvate dehydrogenase kinase enzymes may be an option to overcome 5-FU -mediated chemo-resistant in colorectal cancer.

Taurine attenuates valproic acid-induced hepatotoxicity via modulation of RIPK1/RIPK3/MLKL-mediated necroptosis signaling in mice.

Valproic acid (VPA) is known as a common drug in seizure and bipolar disorders treatment. Hepatotoxicity is the most important complication of VPA. Taurine (Tau), an amino acid, has antioxidant effects. The present research was conducted to evaluate the protective mechanisms of Tau on VPA-induced liver injury, especially focusing on the necroptosis signaling pathway. The sixty-four male NMRI mice were divided into eight groups with eight animals per each. The experiment groups pretreated with Tau (250, 500, 1000 mg/kg) and necrostatine-1 (Nec-1, 1.8 mg/kg) and then VPA (500 mg/kg) was administered for 14 consecutive days. The extent of VPA-induced hepatotoxicity was confirmed by elevated ALP (alkaline phosphatase), AST (aspartate aminotransferase), ALT (alanine aminotransferase) levels, and histological changes as steatosis, accumulation of erythrocytes, and inflammation. Additionally, VPA significantly induced oxidative stress in the hepatic tissue by increasing ROS (reactive oxygen species) production and lipid peroxidation level along with decreasing GSH (glutathione). Hepatic TNF-α (tumor necrosis factor) level, mRNA and protein expression of RIPK1 (receptor-interacting protein kinase 1), RIPK3, and MLKL (mixed lineage kinase domain-like pseudokinase) were upregulated. Also, the phosphorylation of MLKL and RIPK3 increased in the VPA group. Tau could effectively reverse these events. Our data suggest which necroptosis has a key role in the toxicity of VPA through TNF-α-mediated RIPK1/RIPK3/MLKL signaling and oxidative stress. Our findings suggest that Tau protects the liver tissue against VPA toxicity via inhibiting necroptosis signaling pathway mediated by RIPK1/RIPK3/MLKL and suppressing oxidative stress, and apoptosis.

Preadministration of high-dose alpha-tocopherol improved memory impairment and mitochondrial dysfunction induced by proteasome inhibition in rat hippocampus.

Objective: The ubiquitin-proteasome system plays a key role in memory consolidation. Proteasome inhibition and free radical-induced neural damage were implicated in neurodegenerative states. In this study, it was tested whether alpha-tocopherol (αT) in low and high doses could improve the long-term memory impairment induced by proteasome inhibition and protects against hippocampal oxidative stress. Methods: Alpha-tocopherol (αT) (60, 200 mg/kg, i.p. for 5 days) was administered to rats with memory deficit and hippocampal oxidative stress induced by bilateral intra-hippocampal injection of lactacystin (32 ng/µl) and mitochondrial evaluations were performed for improvement assessments. Results: The results showed that lactacystin significantly reduced the passive avoidance memory performance and increased the level of malondialdehyde (MDA), reactive oxygen species (ROS) and diminished the mitochondrial membrane potential (MMP) in the rat hippocampus. Furthermore, Intraperitoneal administration of αT significantly increased the passive avoidance memory, glutathione content and reduced ROS, MDA levels and impaired MMP. Conclusions: The results suggested that αT has neuroprotective effects against lactacystin-induced oxidative stress and memory impairment via the enhancement of hippocampal antioxidant capacity and concomitant mitochondrial sustainability. This finding shows a way to prevent and also to treat neurodegenerative diseases associated with mitochondrial impairment.

Protective effect of naringin against BPA-induced cardiotoxicity through prevention of oxidative stress in male Wistar rats.

Bisphenol A (BPA), which is an applied endocrine disrupting chemical in industry for producing epoxy resins and polycarbonate plastics and naringin, is an active flavanone glycoside of grapefruit and many citrus fruits. The present study evaluated the protective effect of naringin against cardiotoxicity induced by BPA. Male Wistar rats were divided into six groups. Control group received oral olive oil; and BPA group orally were administrated 50 mg/kg of BPA for 30 d consecutively to induce toxicity. 40, 80, and 160 mg/kg of naringin were orally administered for 30 consecutive, along with BPA. Naringin group orally received 160 mg/kg of naringin for 30 d consecutively. Animals were sacrificed and their biochemical, histological, and oxidative stress parameters were measured 24 h after the last treatment. Heart injury was induced by BPA as an evidence with a significant increase in levels of aspartate aminotransferase, lactate dehydrogenase, creatine kinase-MB, triglyceride, lipid peroxidation, and a significant decrease in levels of glutathione, superoxide dismutase, catalase, and glutathione peroxidase and triggered myocardial disorganization, myofibrillar loss, congestion of red blood cells, and the inflammation. However, there were not any changes in the total cholesterol, low-density lipoprotein-cholesterol, high-density lipoprotein-cholesterol, and alanine aminotransferase. Moreover, our results indicated that administering 80 and 160 mg/kg of naringin significantly altered all examined endpoints that were induced by BPA. Both concentrations of 80 and 160 mg/kg of naringin were more effective than 40 mg/kg. These findings indicated that naringin had a protective effect against cardiotoxicity induced by BPA through lipid-lowering properties, antioxidant activity, and suppressed lipid peroxidation.

Metformin in contrast to berberine reversed arsenic-induced oxidative stress in mitochondria from rat pancreas probably via Sirt3-dependent pathway.

Exposure to arsenic has been linked to the development of type 2 diabetes though its mechanism of toxicity remains unresolved. In this study berberine (BBR) effects on arsenic-induced sirtuin 3 (Sirt3) modifications in isolated mitochondria from rat pancreas were evaluated and compared with metformin (MET). With arsenic, mitochondrial reactive oxygen species (ROS), oxidative stress, and insulin resistance were obtained higher than control. From our results and in the presence of arsenic trioxide, insulin resistance and Sirt3 levels were found to be predominantly elevated that could be the result of compensating mechanisms. Apparently, BBR and MET recruit both direct (as an antioxidant) and indirect mechanisms (Sirt3 content) to deal with arsenic trioxide toxicity. Metformin compared with BBR exhibited a less significant effect on ROS levels and since its direct antioxidant property is minor, depressed the ROS level mainly through the Sirt3 modification.

Topical Anti-Inflammatory and Analgesic Activities of Citrullus colocynthis Extract Cream in Rats.

Background and objectives:Citrullus colocynthis (CC), known as bitter apple, is used to treat diabetes in Iranian traditional medicine. The aim of this study is to evaluate the anti-inflammatory and analgesic activities of CC cream in rats. Materials and Methods: The carrageenan-induced edema in a rat hind paw was carried out to evaluate the topical anti-inflammatory effect of the CC fruit extract cream (2⁻8%) and the tissue levels of IL-6 and TNF-α were estimated by using a commercial ELISA kit. The topical antinociceptive activity of CC cream (2⁻8%) was evaluated in the rat formalin test. To determine the role of opioid receptors in the local antinociceptive effect of the CC cream, naloxone (20 µg/paw, i.pl.), a non-selective opioid antagonist, was used. Results: The results showed that the CC cream (2⁻8%) dose-dependently reduced the carrageenan-induced paw edema and reversed the changes in the level of TNF-α and IL-6 due to carrageenan-induced edema (p < 0.01). The anti-inflammatory effect of CC cream 8% was comparable to that of hydrocortisone ointment 1%. Furthermore, the application of CC cream (2⁻8%) dose-dependently inhibited both first and second phases of the formalin test (p < 0.05). The antinociceptive effect of the CC cream (8%) was comparable to that of methyl salicylate cream 30%. Moreover, the administration of naloxone significantly reversed the topical antinociceptive effect of the CC cream (p < 0.05). Conclusions: For the first time, this study indicated that the topical application of CC cream possesses significant anti-inflammatory and antinociceptive activities in animal models, which were probably mediated by opioid receptors and the suppression of pro-inflammatory cytokines (TNF-α and IL-6). Thus, the CC cream can be used to treat inflammatory pain and inflammatory diseases.

Role of berberine against arsenic induced oxidative damage in isolated rat liver mitochondria.

The aim of the present study was to assess the protective role of berberine against toxicity induced by arsenic in mitochondria from liver of rat. The level of reactive oxygen species and mitochondrial membrane potential changes were evaluated spectrofluorometrically. 20, 40 and 100 µM arsenic concentration increased ROS level approximately by 13.5, 21.3 and 29 %. However, when pretreated mitochondria with berberine (10, 25, 50 µM) were exposed to arsenic (20, 40 and 100 µM), ROS production diminished. Also, for all arsenic concentration mitochondrial membrane damage was detected to be 2.5, 4.8 and 7.26 % respectively. Pretreatment with berberine even at highest concentration (50µM) was not able to retain membrane potential as compared to control. These results showed that mitochondria were significantly affected when exposed to arsenic, forcedly directed toward excess ROS production and mitochondrial membrane disruption. Pretreatment with berberine, reduced ROS generation but did not restore mitochondrial membrane integrity.

Investigation on the effect of static magnetic field up to 30 mT on viability percent, proliferation rate and IC50 of HeLa and fibroblast cells.

We have investigated the effects of static magnetic field (SMF) on the viability of the human cervical cancer (HeLa) cell line and fibroblast cells. The cells were cultured in DMEM medium and treated several times (24, 48,72 and 96 h) and at several intensities (5, 10, 20 and 30 mT) of magnetic field (MF). The cytotoxicity and cell viability percent in treated cells were performed using MTT assay by evaluating mitochondrial dehydrogenase activity. The MF ability on inducing cell death or inhibiting biochemical function was reported as cell death percent. The results showed that the increase of MF intensity and the time that cells were exposed to this treatment increased sharply cell death percent and proliferation rate in HeLa cell compare to fibroblast cells. Our data suggest that SMF biological effects on cell death were different in our selected targets. Cell type and time of exposure have been therefore found to be significant factors. These findings could be used to improve new effective method using SMF in conjunction with the common therapeutic approaches.

Cardiovascular and respiratory mortality attributed to ground-level ozone in Ahvaz, Iran.

Ahvaz, the capital city of Khuzestan Province, which produces Iran's most oil, is on the rolls of fame in view of air pollution. It has also suffered from dust storm during the recent two decades. So, emissions from transportation systems, steel, oil, black carbon, and other industries as anthropogenic sources and dust storm as a new phenomenon are two major concerns of air pollution in Ahvaz. Without any doubt, they can cause many serious problems for the environment and humans in this megacity. The main objective of the present study was to estimate the impact of ground-level ozone (GLO) as a secondary pollutant on human heath. Data of GLO in four monitoring stations were collected at the first step and they were processed and at the final step they were inserted to a health effect model. Findings showed that cumulative cases of cardiovascular and respiratory deaths which attributed to GLO were 43 and 173 persons, respectively. Corresponding RR for these two events were 1.008 (95% CI) and 1.004 (95% CI), respectively. Although we did not provide a distinction between winter and summer in case of mentioned mortalities attributed to GLO, ozone concentrations in winter due to more fuel consumption and sub adiabatic condition in tropospheric atmospherewere higher than those GLO in summer.