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Objectives This in vivo study aimed to evaluate the effect of various concentrations of artemisinin (Art) alone or together with N-acetyl cysteine (NAC) on spermatological indices, antioxidant status, and histopathological parameters of testicular tissue in adult male mice. Methods Six groups of five healthy male mice (25–30 g) were randomly assigned to different experimental groups. These groups received DMSO and corn oil (0.1%) as an Art solvent (Control), 50 mg kg−1 Art (Art-50), 250 mg kg−1 Art (Art-250), 50 mg kg−1 Art + 150 mg kg−1 NAC (Art-50+NAC-150), 250 mg kg−1 Art + 150 mg kg−1 NAC (Art-250+NAC-150) and 150 mg kg−1 NAC (NAC-150) for a period of 7 days. Testes and epididymis were prepared to evaluate the malondialdehyde (MDA), glutathione (GSH), superoxide dismutase (SOD), catalase (CAT), peroxidase (POX), spermatological indices, and histological parameters. Results We showed that the high dose of Art (Art-250) significantly reduced the sperm count, motility, viability, and the activity of CAT and increased the levels of MDA compared to the control group. Also, the overdose of Art caused adverse changes in testicular tissue. Co-administration of NAC with Art (Art-250+NAC-150) corrected the adverse effects of Art. Conclusions The current study reports that a high dose of Art affects, spermatological parameters, antioxidant/stress oxidative status of the male reproductive system, and NAC is capable neutralize all adverse effects caused by Art.

Nano silicon dioxide (Nano-SiO2) has a great deal of application in food packaging, as antibacterial food additives, and in drug delivery systems but this nanoparticle, despite its wide range of utilizations, can generate destructive effects on organs such as the liver, lung, and kidney. This study aimed to investigate the toxicological effects of nano-SiO2 through apoptotic factors. For this purpose, 40 female rats in 4 groups (n = 10) received 300, 600, and 900 mg/kg/day of nano-SiO2 at 20–30 nm size orally for 20 days. Relative expression of Caspase3, Bcl-2, and BAX genes in kidney and liver evaluated in Real time-PCR. The Results indicated the overexpression of BAX and Caspase3 genes in the liver and kidney in groups receiving 300 and 900 mg/kg/day of nano-SiO2. Bcl-2 gene was up-regulated in the liver and kidney at 600 mg/kg/day compared to the control group. Overexpression of the Bcl-2 gene in the kidney in 300 and 900 mg/kg/day recipient groups was observed (p ≤ 0.05). Histopathological examination demonstrated 600 mg/kg/day hyperemia in the kidney and lung. In addition, at 900 mg/kg/d were distinguished scattered necrosis and hyperemia in the liver. The rate of Epithelialization in the lungs increased. Our study revealed that the oral consumption of nano-SiO2 can cause respiratory toxicity. The nano-SiO2 at 300 and 900 mg/kg/day can induce more cytotoxicity in the liver and lung after oral exposure. However, cytotoxicity of nano-SiO2 at 600 mg/kg/day in the kidney and lung was noticed. Hence, The Using of nano-SiO2 as an additive and food packaging should be more considered due to their deleterious effects.

Ferroptosis is a form of cell death associated with iron-dependent lipid peroxidation. We used a chicken embryo model to investigate if ferroptosis was implicated in the molecular mechanism underlying the potential effects of maternal exposure to iron oxide nanoparticles (IONPs) on the developing brain. One hundred and eighty fertilized eggs were randomly divided into six groups (30 eggs/group; 10 eggs/replicate). Groups I and II received maghemite (γ-Fe2 O3 ) NPs (MGMNPs), while groups III and IV received magnetite (Fe3 O4 ) NPs (MGTNPs). Both MGMNP and MGTNP were administrated at the concentrations of 100 and 250 ppm. One group (placebo) received saline, and the other remained untreated (control). The compounds were given by in ovo method (0.3 ml/egg) only once on the first day of the embryonic period. Samples from cerebral tissue were collected on day 20 for histopathological, biochemical and gene expression analyses. Total antioxidant capacity (TAC) and malondialdehyde (MDA) increased; glutathione peroxidase (GPX) expression and activity decreased in IONPs-treated groups. Ferroptotic cells appeared in the cerebral tissue following exposure to the low dose of MGMNP and MGTNP. Oxidative stress and ferroptotic cells were more evident for MGMNP compared to MGTNP. The low dose of MGMNP and MGTNP induced more severe oxidative stress in the cerebral tissue. According to the results, maternal exposure to IONPs is associated with ferroptosis in the brain. This work could encourage future researches to investigate inhibitors of ferroptosis as a protective strategy against iron-induced cell injuries and cell death.

One of the primary causes of morbidity and mortality in those with short bowel syndrome (SBS) is sepsis, caused by bacterial translocation (BT). Since synbiotics can cease gut-related bacterial overgrowth, they may serve as a supportive dietary supplement-based strategy after gastrointestinal surgery. This study was conducted to determine the effects of Lactobacillus acidophilus and pectin on BT and gut adaptation after extensive small bowel resection in the rat. Forty rats were distributed in four groups. Group A suffered laparotomy, group B suffered gut transection and reanastomosis, SBS rats (group C) suffered 75% small gut resection, and finally, Group D suffered gut resection and treated with a synbiotic cocktail from day 7 before the surgery to day 14 after it. Intestinal structural changes and BT to mesenteric lymph nodes, liver, portal blood, and peripheral blood were detected on day 15 post-surgery. Treatment with a synbiotic cocktail led to a considerable reduction in bacterial translocation to liver and portal vein (degree II) compared with SBS untreated rats. Also, synbiotic administration significantly increased jejunum and ileum villus height and crypt depth, ileum villus width, and percentage of goblet cells in jejunum and ileum compared with SBS rats. In the rat model of short bowel syndrome, L. acidophilus, and pectin, as a potential synbiotic compound, could decrease the BT from the gut and improve the bowel adaptation.

Objective: To compare the effects of curcumin and nanocurcumin oral supplementation on the muscle healing rate of an animal model of surgical muscle laceration. Methods: Thirty-two male adult rats were randomly divided into sham, control, curcumin, and nanocurcumin groups. Partial transection of the gastrocnemius muscle was made in the right limb of the control and treatment groups. The sham and control groups received normal saline, curcumin group received 500 mg/kg of curcumin and nanocurcumin group received 100 mg curcumin-loaded nanomicelles orally every day. They euthanized two weeks later and the specimens were stained by hematoxylin-eosin (H&E) and Masson’s trichrome methods. Aspartate transaminase (AST) and creatine phosphokinase (CPK) were measured in blood samples. Results: The percentage of collagen fibers in the nanocurcumin group was significantly lesser than the control and curcumin groups (p

Background: The inhibitory effect of Nanoparticles and microparticles of Chitosan on infection due to Cryptosporidium was studied. Methods: For this purpose 30 NMRI mice with 4-6 weeks old were randomly divided into five groups including, uninfected /untreated control group, infected/untreated control group, infected/ treated with chitosan (0.5 mg in per approve), infected/ treated with nano chitosan (0.5 mg in per approve) and infected/ treated with nano chitosan (1 mg in per approve). Except first group, mice were experimentally infected by oral administration of 104 C. parvum oocysts for per animal. Treatment groups were administered with nano chitosan and micro particles of chitosan. The presence of oocyst shedding, weight gain/loss, the histopathology of intestine sections and serology were examined in all groups. Results: There was no significant difference between the mean of weight gain/loss in control and treatment groups. Oocyst shedding was significantly (p

Background: A specific treatment has not yet developed for cryptosporidiosis, and some of the used drugs had side effects in immunodeficient patients. The goal of an appropriate remedy is to remove symptoms and improve immune responses in hosts. The current study was designed to evaluate the therapeutic efficacy of Artemisia spicigera ethanolic extract in experimentally infected immunosuppressed mice. Methods: Thirty six NMRI mice, 4-6 wk old, were randomly divided into six equal groups. C1: uninfected, treated control; C2: infected, untreated control; T1, T2, T3, and P: infected, treated with 0.2, 2, and 20 mg/ml extract, and 5mg/ml paromomycin, respectively. Mice were experimentally infected by oral administration of 104 oocysts/animal of Cryptosporidium parvum and treated orally for eight days per 12h, starting 12h before experimental infection. The presence of oocyst shedding, weight gain/loss, and the histopathology of ileum sections were examined. Results: Results revealed that oocyst shedding was significantly (P

Broilers are more vulnerable to high temperatures than mammals due to the feather cover, lack of sweat glands, fast growth and intensive breeding in commercial systems. Thermal stresses affect the function of various organs and change the expression profiles of hundreds of genes in the different tissues of broilers. Thermal manipulation (TM) during embryogenesis can increase heat tolerance in growing broilers. Small heat shock proteins (SHSPs) are a group of HSPs which participate in many cellular functions like response to different stressors. However, their role in the thermotolerance has not been fully elucidated. Ninety fertilized eggs were randomly divided into three groups (30 eggs/group; 10 eggs/replicate). Normal control (NC) eggs were incubated at 37.5 °C throughout the incubation period whereas heat stress (HS) and cold stress (CS) groups were kept at 41 °C and 33 °C from 15 to 17th day of incubation for 3 h each day, respectively. On day 20, samples from the cerebrums were harvested for histopathology and mRNA expression analyses of HSPB1, HSPB5, HSPB8, and HSPB9. There were no significant differences in survivability, defected embryos, hatchability, and body weight among treatments. TM had no major deleterious effects on the cerebral tissue except for mild degeneration in the HS group. HSPB1, HSPB5, HSPB8, and HSPB9 were expressed in the presence and absence of TM. All SHSP genes tested were downregulated in response to TM except for HSPB9 which was upregulated in the HS group. The highest change in gene expression due to TM observed for HSPB1. This study presents a broader understanding of mechanisms underlying response to TM in broilers. The results suggest that HSPB1, HSPB5, HSPB8, and HSPB9 are involved in thermotolerance in broilers and SHSPs could be involved in the gene expression profiling of TM. It may propose the use of nutritional supplements in the poultry industry to modulate SHSPs.

Present study was conducted to investigate the effects of heat-killed Tsukamurella inchonensis on growth performance, gastrointestinal structure, immune response, and biochemical parameters in rainbow trout. Fish (mean weight 25 g) were fed basal diet (control), diets containing 2.48 × 108 colony-forming units (low-dose group) or 1.24 × 109 colony-forming units (high-dose group) of heat-killed Tsukamurella inchonensis per 1 kg of feed for 90 days. Results showed that growth performance was significantly enhanced in both treatment groups compared to the control group. The intestinal villus length and pyloric cecal fold length were mainly enhanced in the high-dose group. On the other hand, higher goblet cell percentage was shown with administration of dead Tsukamurella inchonensis in both treatment groups. Immune parameters such as alternative complement activity, immunoglobulin level, and hemagglutination titer were significantly higher in treatment groups than in fish fed in the control diet. Meanwhile, feeding heat-killed Tsukamurella inchonensis especially at higher dose caused a decrease in the levels of total cholesterol, uric acid, and lipid peroxidation product whereas no significant changes were noted in serum-specific marker enzymes levels, namely alanine aminotransferase (ALT), alkaline phosphatase (ALP), and aspartate aminotransferase (AST) by feeding both treatment diets compared to the control group. This study suggests that heat-killed Tsukamurella inchonensis especially at 1.24 × 109 colony-forming units had more potential to enhance growth, immunological parameters, and intestinal structure in rainbow trout.

In the current experiment, we investigated the immune-modulatory potential of mesenchymal stem cells (MSCs) and conditioned media (CM) in attenuating of chronic asthmatic changes in a rat model. Male rats were divided into control (C) and ovalbumin-sensitized (S) groups, which further allocated into three subgroups; rats received systemically 50 μl volume of PBS (C and S groups), CM (CSV and SSV groups) and rats received intravenous infusion of 2 × 106 bone marrow-derived mesenchymal stem cells (rBMMSCs) (CCV and SCV groups). Two weeks later, the expression of interleukin (IL)-4, IL-13, and IL-10, miRNA133, and miRNA155 was measured by real-time PCR. Pathological changes and the recruitment of rBMMSCs into pulmonary parenchyma were evaluated by histopathological and immunofluorescence analyses, respectively. The systemic injection of rBMMSCs, but not CM, decreased the levels of IL-4, IL-13, IL-10, miRNA133, miRNA155 and reduced pathological changes in sensitized rats as compared with other sensitized groups (p < 0.001 to p < 0.05). rBMMSCs transmigrated to lung tissue in cell-administrated rats, albeit intensity of asthmatic changes, in turn, affected the amount of recruited cells. Collectively, our data suggest the potential role of MSCs, but not CM, in reducing pathological changes possibly via the modulation of miRNA133 and miRNA155 during asthmatic changes.

Objective-The objective of this study was to compare effects of olive oil and lime water combination with silver sulfadiazine in third-degree burn healing. Design-Randomized experimental study. Animals-Sixty-three adult male Bulb/C mice weighing25±5 gr. Procedures-The mice were anesthetized with an intraperitoneal injection of ketamine 10% and xylazine 2% combination and the third-degree burn wound was created in the area of 1×1 cm at the dorsum of the animals using an innovated electrical device. There were three groups of 21 as follows: Group I–Negative control; which received the topical normal saline solution, Group II–Positive control; with the daily topical application of silver sulfadiazine ointment, and Group III–Treatment; which was received topical olive oil plus lime water, daily. Each group was divided into three subgroups and topical treatments or saline were applied to each subgroup for 7, 14, and 21 days, respectively. No other dressing was used. The mice of each subgroup were sacrificed on days 7, 14, and 21 and hematoxylin-eosin (H&E) stained slides were prepared. Histopathologic evaluations include epidermal thickness, secondary infection, and percentage of collagen, ground substance, fibroblast, and blood vessels. Results-Group II showed significantly less secondary infection, and secondary infection in group III was significantly reduced compared to group I. The epidermal thickness of group III had a significant difference with group II at 2nd week. Both group II and III were induced more collagen synthesis at 2nd week compared to group I. This was also true about ground substance. Group III had more angiogenesis at 2nd week compared to others, but ultimately this difference was diminished. Conclusions and Clinical Relevance-Despite lime water has some cytotoxic effects, combining with olive oil can reduce these unwanted effects. Thus, the combination may be beneficial in third-degree burn wounds in mice compared to routinely used silver sulfadiazine therapy.

Background The major feature of asthma is governed by chronic airway inflammation. This investigation was proposed to achieve the suitable candidate for ameliorating long-term chronic asthmatic changes of respiratory tract. Methods 36 rats were classified into healthy (C) and ovalbumin (OVA)-sensitized animals (S). To sensitize, the rats were exposed to OVA over a course of 32 ± 1 days. One day after sensitization, equal six different groups were subjected to experimental procedure (n = 6); Rats only received intratracheally 50 ml PBS (CPT and SPT groups), 50 μl conditioned medium (CM) (CST and SST groups) and 50 μl PBS containing 2 × 106 rat bone marrow-derived mesenchymal stem cells (rBMMSCs) (CCT and SCT groups). Two weeks after treatment, tracheal responsiveness, immunologic responses and recruitment of rBMMSCs into the lung as well as pathological changes were evaluated. Results A high degree of tracheal responsiveness, total white blood cell and percentages of eosinophil and neutrophil was significantly recorded in all sensitized groups rather than of controls (p

Linguatula serrata is a cosmopolitan zoonotic parasite in which carnivores and herbivores serve as final and intermediate hosts, respectively. The aim of this study was to compare the L. serrata nymphal infection rate and intensity of infection (mean number of nymphs ± standard error) to the appearance and pathological changes of mesenteric lymph nodes (MLNs) infected with L. serrata using sheep slaughtered in Tabriz, Iran. In addition, the effect of age, sex, and season on the prevalence of L. serrata infection was evaluated. For this purpose, over a four-year period, 31,078 MLNs from 3,199 sheep were examined, with 4,972 (15.99%) MLNs infected representing 518 (16.20%) sheep. Collected MLNs were categorized by color as normal, red or black and by consistency as normal, soft or hard. L. serrata were found in 8.88% of normal-colored MLNs, 14.45% of red (hemorrhagic) MLNs and 44.57% of black-colored MLNs, with the difference being significant for infection and infection intensity (P

Tilorone dihydrochloride is a therapeutic agent with a different mechanism in cancer. The species of Lactobacillus have an important role in cytotoxic effect.Because of unknown effects of tilorone and culture supernatants from Lactobacillus reuteri on hepatoma, the aim of this study is to evaluate apoptotic, cytotoxic, and therapeutic effects of tilorone on mouse hepatoma cell line with and without culture supernatants from L. reuteri.To do so, after cell line culture, cells were divided into different groups such as negative control, treatment with four doses of tilorone, positive control of supernatant (single dose), and combination therapy groups of different doses of tilorone with supernatant (constant doses), for 48 h. All groups were studied with pathologic tests, biochemical study, tetrazolium dye (3-(4, 5- dimethylthiazol -2-yl)-2, 5-diphenyltetrazolium bromide [MTT]) assay, and absolute real-time-polymerase chain reaction (RT-PCR) were done to assess Bax and Bcl-2 genes expression, as molecular studies.MTT assay results revealed that the tilorone tissue culture ICBased on these results, it appeared that this agent could be a good candidate for further evaluation as effective chemotherapy acting through the induction of apoptosis in hepatoma. The cell death caused through bacterial supernatant was rather necrosis than apoptosis.

The effects of hesperetin plus naringenin, orange juice and grapefruit juice on mRNA expression of TNF-α, TGF-β1 and TTF-1 in a house dust mite (HDM)-induced asthma animal model were investigated. Interventional mice exposed to HDM for 6 weeks received hesperetin plus naringenin, orange plus grapefruit juice, orange juice, grapefruit juice or water during the last 4 weeks, whereas non-asthmatic control mice consumed water. Lung tissue TNF-α and TGF-β1 expressions in supplemented groups were significantly reduced (p

In the present study, the preventive effect of two different concentrations of α-hederin, the active constituent of Nigella sativa, on lung inflammation and blood cytokines in ovalbumin sensitized guinea pigs was examined. Forty eight male adult guinea pigs were divided into control (C), sensitized (S) and sensitized pretreated groups; with thymoquinone (S+TQ), low dose (S+LAH) and high dose of α-hederin (S+HAH) and inhaled fluticasone propionate (S+FP). The lung histopathology and blood levels of IL-4, IFN-γ and IL-17 were assessed. Compared to sensitized animals, all pathological changes improved significantly in pretreated groups (p < 0.001 to p < 0.05). These improvements in α-hederin pretreated groups were similar to S+TQ and S+FP groups except cellular infiltration in S+LAH and S+HAH groups which was lower than S+TQ group (p < 0.05). The blood IL-4 and IL-17 levels in S+HAH groups showed a significant decrease compared to S group (p < 0.05) which were similar to S+TQ and S+FP groups. The level of IFN-γ in S+LAH and S+HAH groups increased significantly compared to S group (p < 0.05) which was higher than S+FP group (p < 0.05). Blood IL-4 in S+HAH group was significantly lower than S+LAH group (p < 0.05). In conclusion, α-hederin could attenuate the lung inflammation and improve the changes of cytokines like thymoquinone and fluticasone in used dosages.

Objective- This research was conducted to study the effect of flunixin meglumine and ketoprofen on the healing of excisional wounding in the tendon of rats. Design- Experimental study. Animals- Twenty rats were equally divided into four groups of control, placebo (excised tendon receiving saline solution), flunixin and ketoprofen. Procedures- Right Achill complex of all groups underwent full thickness tenotomy. All the rats, except control group, received normal saline, flunixin meglumine or ketoprofen, respectively after operation for 7 days. After euthanasia of all animals on the day 15, the Achill complex was dissected free and prepared for histopathologic study. Neovascularization, edema and inflammatory cell infiltration, fibrin layer formation as well as fibroblast and fibrocyte counts were considered for the evaluation of healing process. Neovascularization, edema and inflammatory cell infiltration were scored from 0 to 3. Results- Results showed no significant change in number of fibroblasts between the groups. Reduced angiogenesis in both treatment groups of non-steroidal anti-inflammatory drugs (NSAIDs) was observed. Conclusion and Clinical Relevance- Our findings showed that anti inflammatory effects of ketoprofen is slightly more potent than flunixin meglumine, although differences were not statistically significant.

We investigated whether flavanones, hesperetin–naringenin, orange, and grapefruit juices reduce airway inflammation and remodeling in murine chronic asthma model. To establish chronic asthma, mice received house dust mite (HDM) for 3 days in 2 weeks, followed by twice per week for 4 weeks. Concurrently, during the last 4 weeks, mice received hesperetin plus naringenin (HN), orange plus grapefruit juice (OGJ), orange juice (OJ), or grapefruit juice (GJ); whereas the asthmatic control (AC) group and non-asthmatic control (NC) group consumed water ad libitum. In histopathological examination, no goblet cells metaplasia was observed in the HN, OJ, and GJ groups; also, intra-alveolar macrophages decreased compared with those of the AC group. Hesperetin plus naringenin significantly decreased subepithelial fibrosis, smooth muscle hypertrophy in airways, and lung atelectasis compared with the AC group. Also, there was a reduction of subepithelial fibrosis in airways in OJ and GJ groups compared with AC group, but it was not noticed in OGJ group. In bronchoalveolar lavage fluid, macrophages numbers decreased in OJ and OGJ groups, whereas eosinophil numbers were increased in OJ group compared with NC group. Our finding revealed that hesperetin plus naringenin ameliorate airway structural remodeling more than orange juice and grapefruit juice in murine model of HDM-induced asthma. Copyright © 2015 John Wiley & Sons, Ltd.

Testicular torsion is a consequence of spermatic cord twisting which causes progressive damage to the structure of the testis and reduces sperm quality and usually results in infertility. In the present study, with the assumption of the protective effects of L-carnitine and betamethasone against ischemia-reperfusion (IR) injuries, their effects on twisted testicles were evaluated and compared. Twenty Wistar rats were randomly divided into four groups and used in this study. Except for the Sham (S) group, testicular IR was induced surgically in three other groups, including Control (C), Betamethasone (BM), and L-carnitine (LC) groups. Betamethasone and L-carnitine were injected before detorsion in the BM and LC groups, respectively. After twelve hours of reperfusion, the testicles were detached, and prepared for sperm parameters evaluation such as sperm count, motility, viability, morphology, and chromatin quality, and histopathologic evaluations, including mean seminiferous tubular diameter (MSTD), germinal epithelial cell thickness (GECT), and Johnsen’s mean testicular biopsy scoring (MTBS). The MSTD, GECT, and healthy sperms in the C group were significantly lower than the other groups, while the BM and LC groups were significantly different from others in MTBS. The number of sperms and sperm motility in the BM group was significantly higher than the C group. Sperm viability in the BM and LC groups were significantly higher than the C group. The results of this study showed that both L-carnitine and betamethasone similarly can be effective in treating testicular IR injuries.

Background: Asthma is a chronic lung inflammatory disease driven by over-activation of T helper 2 (Th2) cells. Myeloid-derived suppressor cells (MDSCs) are innate immune cells characterized by their potential to suppress T-cell response. objective: To characterize MDSCs accumulation and function in allergic asthma in vivo. Methods: Allergic airway inflammation was induced in mice by ovalbumin (OVA) and house dust mite (HDM) challenge. MDSC accumulation was quantified by flow cytometry. To assess the functional in vivo impact, MDSCs were adoptively transferred intravenously (IV) or intratracheally (IT). Results: Our studies demonstrate that neutrophilic MDSCs (PMN-MDSCs) are decreased in the bronchoalveolar lavage fluid (BALF) and lungs of allergic airway inflammation in vivo. IV- or IT-transferred PMN-MDSCs were recruited to the lungs and BALF of asthmatic mice and suppressed the infiltration and local activity of Th2 and Th17 inflammatory cells. Adoptively transferred PMN-MDSCs reduced PAS-positive cells, pulmonary histopathological inflammatory scores and ameliorated airway hyperresponsiveness in asthmatic mice. Infiltration of inflammatory cells and pro-inflammatory cytokines released in BALF as well as expression of lung inflammatory transcription factors was decreased after PMN-MDSCs transfer. Arginase1, nitric oxide synthase 2, Cyclooxygenase 2 and A20 pathway were involved in the anti-inflammatory role of MDSCs in asthmatic mice. Conclusions: Collectively, our results demonstrate that MDSCs suppress Th2-dominant inflammation and improve lung function in asthmatic mice in vivo. Adoptive cellular transfer of MDSCs may represent an attractive therapeutic strategy for allergic asthma.

Pre parturition and newborn period events like infectious stresses have important effects on the future life of an offspring. LPS can be a cause of bacterial stress in the body. Silymarin is an herbal substance that has some therapeutic effects on body. According to our literature review there was no any study available about silymarin preservative and useful effects after LPS intervention on fetuses in their future life.Mice of both sex with 25-30 g weight were kept with each other for breeding and the first day of pregnancy was ascertained by observation of vaginal plaque.Silymarin was suspended in normal saline and then administered to pregnant mice (100 and 250 mg/kg) by stomach gavage for 5 days. Pregnant mice received LPS by one intraperitoneal injection (300 and 500 μg/kg). Half of the offspring's were used for blood sampling for immunologic tests 1.5 hour after immune system stimulation (IP injection of LPS with the dosage of 500 μg/Kg in the day 67 after their birth) IL-1β, TNF-α and IL-6 were measured in them with indirect ELISA kits. Another half of the litters were killed in 70th day of their life (after 3 days of new LPS injection) and whole brain and a specimen from their left lobe of liver was put into neutral buffered formalin.LPS has caused hyperemia and inflammation in the brain, meninges and liver of treatment groups. Silymarin managed to control the effects of LPS stress on the second generation (received LPS when they were fetus) in a dose dependent manner.Stresses of mothers during pregnancy can alter in normal physiology of the offspring's and increase the probability of illness in them in the future. These mothers and their litters has an increased level of proinflammatory cytokines in their serum. Silymarin can be useful for protecting the offsprings from LPS effects in the future life.

The present study was conducted to investigate the effects of gamma irradiation on Ichthyophthirius multifiliis trophonts and to determine the effects of exposure on inactivated parasites in rainbow trout. In the first trial, fish were treated with irradiated Ichthyophthirius multifiliis trophonts for 21 days. Results showed that irradiation at doses of 150 Gy and higher was required to inactivate Ichthyophthirius multifiliis trophonts. The LD50 value obtained was 52.2 Gy. In the second trial, the effects of irradiated Ichthyophthirius multifiliis trophonts on physiological and biochemical components of blood and mucus, as well as skin morphology, were studied for 30 days. Results showed that total protein levels increased in fish exposed to 100 and 150 Gy irradiated trophonts. Fish exposed to 150 Gy treated parasites showed significant increases in serum lysozyme activity. Serum alkaline phosphatase levels were significantly lower in the treatment groups. In the skins of fish exposed to 100 and 150 Gy irradiated trophonts, a higher percentage of goblet cells was observed. Mucus protease and esterase levels were also higher in the treatment groups compared to the control group on days 20 and 30. This suggests that rainbow trout appear to benefit from treatment with gamma-irradiated Ichthyophthirius multifiliis trophonts, especially at 150 Gy.

Gene modified or cytokine activated mesenchymal stem cells (MSCs) have been used as a treatment in various types of cancer. Moreover, irradiation is usually applied as either a standard primary or adjuvant therapy. Here, we showed that the expression of TNF related apoptosis-inducing ligand (TRAIL) and Dickouf-3 (Dkk-3), the promising anticancer proteins, increased in murine adipose-derived mesenchymal stromal cells (AD-MSCs) following activation with TNF-α, resulting in the induction of apoptosis in cancer cells. Also, anticancer effects of TNF-α activated AD-MSCs were intensified with irradiation. In vivo results showed that TNF-α preactivated AD-MSCs combined with irradiation decreased tumor size and increased survival rate in tumor bearing mice. On the other hands, both TNF-α preactivated AD-MSCs with or without irradiation prevented metastasis in ling and liver, and increased apoptosis in tumor mass. Finally, flowcytometry assay demonstrated that naïve AD-MSCs combined with irradiation but not TNF-α activated MSCs with irradiation increased Treg population in lymph node and spleen. Altogether, obtained results suggest that TNF-α activated MSCs combined with irradiation therapy can serve as new strategy in breast cancer therapy.

This study examined the effects of Hilyses™, fermented Saccharomyces cerevisiae (S. cerevisiae), on rainbow trout growth performance, haematological parameters, digestive enzyme activities and gastrointestinal structure. Rainbow trout (mean weight 100–110 g) were fed dietary Hilyses™ (5 g kg−1) and control diet without Hilyses™ for 50 days. Results of this study demonstrated that yeast supplementation in treatment group resulted in increased feed intake, followed by improved feed conversion ratio (FCR) and growth performance. Significant increases were also observed in trypsin and amylase activities in juvenile fish fed treatment diet. Light microscopy demonstrated that both groups of fish displayed normal morphology of proximal intestine and pyloric caeca. In yeast-treated group, higher density of the goblet cells per villus in the proximal intestine was shown. No effects on haematological parameters and carcass chemical composition were noted. It is therefore possible to use fermented S. cerevisiae supplementation to significantly improve the gastrointestinal structure and growth performance in rainbow trout.

Present study examined the effects of Ergosan on growth performance, digestive enzyme activities, hematological parameters and gastrointestinal structure of rainbow trout. Rainbow trout (mean weight 100–110 g) were fed basal diet (control) and diet treated with Aquavac Ergosan (5 g kg−1 of diet) for 50 days. Results of this study showed that Ergosan supplementation significantly increased weight gain (94.27 g vs. 65.04 g), specific growth rate (4.09 vs. 3.10) and feed intake (136.85 g vs. 111.22 g) and decreased feed conversion ratio (1.43 vs. 2.03) compared to control (P

Background: A precise understanding of the mechanism of human neointimal stenoses and atherosclerotic fibrous plaques, which give rise to thromboses in vital arteries, requires a suitable animal model that would mimic the same characteristics well. We developed a rabbit model of neointimal stenosis and fibrotic plaque rupture in the carotid artery to visualize the lesion progress and to characterize the lesion types according to the American Heart Association classification. Methods: Twenty-eight healthy male New Zealand white rabbits were randomly divided into two groups: The rabbits in group A (n = 14) consumed a standard chow diet, and those in group B (n = 14) were injured via perivascular cold injury using liquid nitrogen at the right common carotid artery before being fed a high cholesterol diet (1.5%) for eight weeks. Plasma lipid evaluation was performed before the sacrificing of the rabbits. At the end of every week, at least 1 rabbit from group B was sacrificed for an analysis of lesion histopathology and calculation of the area ratios of the intima to media. Results: The plasma lipid level in group B was significantly higher than that in group A (p value < 0.05). The histopathological results revealed atherosclerosis characteristics such as endothelial layer destruction, fatty streaks and lipid-containing macrophages (foam cells) formation in the intima and media layers, extracellular lipid collections, smooth muscle cells proliferation and migration, neointima formation, intima thickening and deformation, fibrotic plaque formation, and finally plaque rupture. Statistical analysis revealed a significant increase in the intima-to-media ratio at the end of the eighth week (6.41 ± 0.27, p value < 0.05). Conclusion: We successfully developed a rabbit model of neointimal stenosis and atherosclerotic fibrous connective tissue plaque rupture, which is not only quickly and easily reproducible and inexpensive but also without mortality. The merits of our model render the evaluation of neointimal stenoses and fibrotic plaques and their treatment strategies more feasible in humans.

Gastric cancer is often diagnosed at advanced stages and there is no accurate method for its screening and diagnosis, especially in small animals. Here, we explain the application of B-mode ultrasound imaging (BMUI) for screening of gastric changes in the rat. Thus, male Albino Wistar rats, weighing 100-120 grams were randomly divided into two groups. The control group rats (n=10) were given water as routine; the remaining (n=90), were given N-methyl-N-nitro-N-nitrosoguanidine (MNNG, 100 μg/mL) in drinking water ad libitum for 40 weeks. Fifteen rats were killed at different time intervals and the others were sacrificed after 55 weeks. The BMUI of the stomach of animals after MNNG administration show some changes compared with the normal groups. Pathologic investigations of the stomach indicate cancer induction at different levels. The sensitivity and specificity of BMUI is 96.6% and 78.78%, respectively. Thus, it is a useful method of diagnosis of gastric cancer in rats.

Artemisinin has been used for centuries to treat malaria, intestinal tract helminthosis, diarrhea, and used as an antipyretic and sedative agent, but the usage in veterinary medicine is a new field. Recently, it has been used successfully to control experimental poultry coccidiosis. The present study aimed to determine the effects of different doses of artemisinin in broiler chickens with chronic usage. Sixty birds divided into one control and four treatment groups that fed rations mixed with artemisinin at doses of 17, 34, 68, and 136 ppm for 36 days. During the experiment, birds showed no clinical signs except anemia. In microscopic examinations, heart, lung, and spleen had no lesion, but liver, kidney, and brain showed various lesions. Degenerative lesions like intracytoplasmic eosinophilic inclusions were seen in both kidney and liver but fatty change was seen only in liver. There was no relationship between severity of the liver lesions and drug dosage. Central chromatolysis, scattered neuronal necrosis, and mild spongy changes were observed in five regions of the brain that were chosen for sectioning (motor cortex, cerebellar nuclei, midbrain nuclei, and hindbrain nuclei at two separate levels). Severity of lesions in brain was dose-dependent, and cerebral cortex was the most vulnerable area. Haematologic tests showed lower values for hematocrit and red blood cell count dose-dependently. In conclusion, artemisinin is a promising drug for prevention and control of coccidiosis in broiler chickens and its side effects are not too much serious especially at therapeutic doses.

Histopathological alterations in rainbow trout, Oncorhynchus mykiss (Walbaum, 1792), induced by irradiated alginic acid By M. Heidarieh, F. Daryalal, A. R. Mirvaghefi, A. A. Shahbazfar, S. Moodi and H. Heidarieh Agricultural Research School (ARS-NSTRI), Karaj, Iran; Department of Fisheries and Environment Science, Natural Resources, University of Tehran, Tehran, Iran; Department of Veterinary Medicine, University of Tabriz, Tabriz, Iran; Student of DVM, Islamic Azad University, Branch of Kazeroon, Kazeroon, Iran

The present study aimed to find LD of artemisinin and to characterize the single dose toxicity of 50 the drug following oral exposure. 49 day-old Ross broilers divided into 7 groups; one control, one drug vehicle and five treatment groups. The treatment groups received artemisinin alcoholic solution at doses of 10, 50, 250, 1250 and 2500 mg/kg on day 30 by a crop tube. The control and drug vehicle groups received normal saline and ethyl alcohol, respectively. In the period of study just in 1250 and 2500 mg/kg groups there were a few transient neurological signs like depression and unconsciousness. These signs were also observed in drug vehicle group. None of the birds died, so they were euthanised on day 40. In microscopic examination, only in treatment groups a slight degeneration in liver and kidney as intracytoplas mic eosinophilic inclusions, hepatocellular swelling and bile retention in liver were evident. In brain central chromatolysis, scattered neuronal necrosis, spongy change and focal axonal swelling were observed. It is concluded that artemisinin has a good margin of safety in poultry but in very high doses it may cause some adverse effects.

Background/aim The aim of the present study was to examine the anticancer effects of combination treatment with artemisinin and iron on the human gastric cancer cell line. Materials and methods The AGS cell line was cultivated separately as a monolayer in culture flasks and different doses of 99% pure artemisinin with invariable doses of iron sulfate were added to the culture media and adhesive cells on the flask's bottom were stained with hematoxylin-eosin for a pathological assay. Results Damage to cancerous cells increased dose dependently and it was higher in the combination treatment groups (artemisinin plus iron). The histopathological changes were observed specially in the groups with high artemisinin concentration as cell swelling, nucleus swelling, and formation of small and large vacuolization. Necrotic changes as nucleus pyknosis were seen too. Changes in groups receiving both artemisinin and iron gradually became more severe with dose increase. Conclusion Pathologic studies showed that the cytotoxic effects of artemisinin were dose dependent and the presence of iron enhanced the artemisinin's anticancer potency.

Diabetes mellitus is a major cause of serious micro- and macrovascular diseases that affect nearly every system in the body, including the respiratory system. Non-enzymatic protein glycation due to hyperglycaemic stress has fundamental implications due to the large capillary network and amount of connective tissue in the lung. The current study was designed to determine whether leucine, zinc, and chromium supplementations influence the function and histological structure of the respiratory tract in a rat model of type 2 diabetes. Seventy-seven rats were divided into eleven groups, consisting of 7 animals each. One group served as negative control and insulin and glibenclamide were used as positive control drugs. Thus, eight groups received the nutritional supplements alone or in combination with each other. Nutritional supplements and glibenclamide were added to the drinking water and neutral protamine Hagedorn insulin was subcutaneously injected during the 4 weeks of treatment period. The induction of type 2 diabetes in the rats caused an infiltration of mononuclear cells and edema in the submucosa of the trachea and lung, severe fibrosis around the vessels and airways, and perivascular and peribronchial infiltration of inflammatory cells and fibrin. In the diabetic group, the total inflammation score and Reid index significantly increased. Diabetes induction significantly reduced the total antioxidant status and elevated the lipid peroxidation products in the serum, lung lavage and lung tissue of the diabetic animals. Treatment with nutritional supplements significantly decreased the histopathological changes and inflammatory indices in the diabetic animals. Supplementation of diabetic rats with leucine, zinc, and chromium, alone and in combination, significantly increased the total antioxidant status and lipid peroxidation level in the diabetic animals. The nutritional supplements improved the enzymatic antioxidant activity of catalase, glutathione peroxidase, myeloperoxidase, and superoxide dismutase in the diabetic rats. The present results demonstrate beneficial effects and amelioration of inflammation in the respiratory system of type 2 diabetic rats by leucine, zinc, and chromium supplements, probably due to their hypoglycaemic and antioxidant properties. Using safe and effective nutritional supplements, such as leucine, chromium and zinc, to replace proven conventional medical treatments may help to control diabetes and/or its complications.

Gordonia bronchialis is a Gram-positive, weakly acid-fast species of the genus Gordonia within the sub-order Corynebacteriaceae of the order Actinomycetales. It is an environmental organism that rarely gives raise to human infections (Arenskotter et al. 2004). Killed preparations of G. bronchialis and some other genera within the order Actinomycetales are potent immune modulators useful in the prevention and treatment of many immune-related diseases in laboratory animal and veterinary medicine (Fontanella et al. 2007; Davila et al. 2011; Marro et al. 2011; Stanford and Stanford 2012; Smaldini et al. 2013). In aquaculture, G. bronchialis improved survival and weight gain in shrimp and young fish, enhanced growth rate and color in Koi carp and reduced its skeletal abnormalities (Stanford and Stanford 2012). There are some studies regarding the effects of immunostimulatory substances on the metabolism of aquatic animals (Castexa et al. 2009; Harikrishnan et al. 2010; Lazado et al. 2010; Weifen et al. 2012). Since there is no information about the effect of G. bronchialis on fish biochemical indices, in the present study the effect of dietary inclusion of heatkilledG. bronchialis on the serum antioxidant activity, serum-specific marker enzymes such as alkaline phosphatase and aspartate aminotransferase, and serum metabolites (triglycerides, cholesterol, uric acid, and glucose) of juvenile rainbow trout was investigated. Furthermore the growth performance and gastrointestinal structure of juvenile rainbow trout fed with heat-killed G. bronchialis was also determined.

We investigated whether flavanones, hesperetin-naringenin, orange, and grapefruit juices reduce airway inflammation and remodeling in murine chronic asthma model. To establish chronic asthma, mice received house dust mite (HDM) for 3 days in 2 weeks, followed by twice per week for 4 weeks. Concurrently, during the last 4 weeks, mice received hesperetin plus naringenin (HN), orange plus grapefruit juice (OGJ), orange juice (OJ), or grapefruit juice (GJ); whereas the asthmatic control (AC) group and non-asthmatic control (NC) group consumed water ad libitum. In histopathological examination, no goblet cells metaplasia was observed in the HN, OJ, and GJ groups; also, intra-alveolar macrophages decreased compared with those of the AC group. Hesperetin plus naringenin significantly decreased subepithelial fibrosis, smooth muscle hypertrophy in airways, and lung atelectasis compared with the AC group. Also, there was a reduction of subepithelial fibrosis in airways in OJ and GJ groups compared with AC group, but it was not noticed in OGJ group. In bronchoalveolar lavage fluid, macrophages numbers decreased in OJ and OGJ groups, whereas eosinophil numbers were increased in OJ group compared with NC group. Our finding revealed that hesperetin plus naringenin ameliorate airway structural remodeling more than orange juice and grapefruit juice in murine model of HDM-induced asthma.

BACKGROUND: Chronic obstructive pulmonary disease is an inflammatory lung disease mainly caused by tobacco smoke inhalation.METHODS: Fifteen healthy adult male cats were categorized into 3 groups: (1) control group, (2) exposed to cigarette smoke (CS), and (3) exposed to CS treated with tiotropium.RESULTS: Increases in clinical signs and airway responsiveness in CS cats were found compared to control animals. The airway hyperresponsiveness and clinical signs were significantly attenuated by treatment with tiotropium. The CS-induced pulmonary release of interleukin-6, interleukin-8, monocyte chemotactic protein-1, and tumor necrosis factor alpha was reduced in the tiotropium group. Exposure to CS significantly increased total inflammatory cells number in bronchoalveolar lavage fluid, which was significantly attenuated by treatment with tiotropium. The number of macrophages, eosinophils and neutrophils and lymphocytes was increased after exposure to CS. Tiotropium significantly reduced the number of all these cells. Perivascular, peribronchiolar infiltration of inflammatory cells and Reid index increased in the CS group. Treatment with tiotropium significantly reduced these parameters to control level. Enhanced lipid peroxidation with concomitant reduction of antioxidants status was observed in the CS group. Tiotropium significantly reduced the serum, lung lavage, lung, and tracheal tissue lipid peroxides to near control levels. Tiotropium also decreased lung and tracheal protein leakage, and prevented the reduction of total antioxidant status in serum, lung lavage, lung and tracheal tissue of the CS group.CONCLUSION: Cigarette smoke increases airway responsiveness and inflammation in a cat model of CS induced lung inflammation. It can effectively be reduced by treatment with tiotropium.

A 3-year-old female goat was referred to the veterinary hospital of Tehran University with a history of respiratory problems, emaciation, and poor body condition. At necropsy, the lungs were heavier than normal and showed grayish sulfur granules. The pleura had adhesion to the thoracic wall with fibrous tissue. The heart was partly flaccid and had serous atrophy of fat at the base. In microscopic sections, granulomatose pneumonia with club shape colonies and asteroid bodies were obvious. Tissue gram staining showed gram-negative colonies. Bacterial culture and biochemical tests directed us to Actinobacillus pleuropneumoniae as cause of pneumonia in the goat.

This study investigated the therapeutic effect of dual-frequency sonication (3 MHz and 28 kHz) at low intensity levels in combination with micellar doxorubicin in the treatment of a tumor model of spontaneous breast adenocarcinoma in Balb/c mice.We used sonication frequencies 28 kHz and 3 MHz and their dual combinations in the progressive wave mode to enhance acoustic cavitation. Then, the antitumor effect of the simultaneous dual-frequency ultrasound (28 kHz and 3 MHz) at low intensity levels in combination with doxorubicin and micellar doxorubicin injection was investigated in a spontaneous model of breast adenocarcinoma in Balb/c mice. Sixty-three tumor-bearing mice were randomly divided into seven groups: control, sham, sonication with dual frequency, doxorubicin without sonication, doxorubicin with dual-frequency sonication, micellar doxorubicin without sonication, and micellar doxorubicin with dual-frequency sonication. The tumor volume change relative to the initial volume, tumor growth inhibition ratio, the required times for each tumor to reach two (T 2) and five (T 5) times its initial volume, and survival period were the tumor growth delay parameters which were calculated and recorded at various times after treatment.The results of the combination of frequencies 28 kHz (0.04 W/cm(2)) and 3 MHz (2.00 W/cm(2)) showed remarkable enhancement of the cavitation activity compared with single-frequency sonication (P 0.05). The micellar doxorubicin injection with sonication group showed a significant difference in the relative volume percent parameter compared with the other groups (P 0.05). Additionally, the T 2 and T 5 times in the micellar doxorubicin with sonication group were significantly higher than in the other groups (P 0.05). Also, the survival period of the mice in the micellar doxorubicin with sonication group was significantly longer than in the other groups (P 0.05). These findings were verified histopathologically.This study shows that simultaneous combined dual-frequency ultrasound sonication in continuous mode is effective in producing cavitation activity at low intensity. We conclude that dual-frequency sonication with micellar doxorubicin injection extends survival in a murine breast adenocarcinoma model.

Artemisinin is a sesquitrepenelactone with an endoperoxide bridge. It is a naturally occurring substance from Artemisia species plants. Artemisia species have been used in oriental medicine for centuries to treat malaria, gastrointestinal helminthosia, diarrhea, and as an antipyretic and sedative agent. Antileishmanial activity of the plants has been announced a few years ago. Dogs are the most important reservoir of leishmaniasis in some parts of the world. To use it as an antileishmanial drug in dogs, its side effects on different organs, among them the kidney as the organ of elimination have to be elucidated. Artemisinin with different concentrations (0.15, 0.3, 0.6 and 1.2 μg/ml) was added to the culture of MDCK (Madin darby canine kidney) cells with and without iron (86 μg/dl). All the changes were controlled and photographed every 12 hours using an invert microscope. After 60 hours, supernatants and cell extracts were examined for LDH (lactate dehydrogenase) concentration and total protein. Also TBARS (thiobarbituric acid reactive substances) test was performed on cell extracts. Some microscopic slides were prepared from the cells and stained with hematoxylin-eosin for microscopic exams. Biochemical parameters showed cellular reaction and injury in a concentration dependent manner. Cell injury was more severe in the iron-added groups. Microscopic exams showed cell and nuclear swelling, granular degeneration, vacuole and vesicle formation, cellular detachment, piknosis, karyorrhexis, cellular necrosis and inhibition of new mitosis. On using the drug for leishmaniasis treatment in the dog, it should be done with caution and supervision.