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Methylmercury (MeHg) is an extremely important environmental toxicant posing serious health risks to human health and a big source of environmental pollutant. Numerous evidence available showing a link between nervous system toxicity and MeHg exposure. Other forms of mercury are reason of metabolic toxic effects and alteration of DNA in the human body. The sources of exposure could be occupational or other environmental settings. In the present study MeHg was orally gavaged to mice, at doses of 2.5, 5, and 10 mg/kg for 4 weeks. Fasting hyperglycemia, activity of hepatic phoshphoenolpyruvate carboxykinase and glucose 6-phoshphate were reported high as compared to control group. Inflammatory markers like, tumor necrosis factor α, the actual end product of inflammatory mediators' cascade pathway was also raised in comparison to control group. Hyperinsulinemia observed in serum showed clear understanding of mercury induced insulin resistance. Moreover, tissue damage due to increased oxidative stress markers like, hepatic lipid peroxidation, 8-deoxygunosine, reactive oxygen species, and carbonyl groups was significantly higher as compared to control group. MeHg caused a significant reduction in antioxidant markers like ferric reducing antioxidant power and total thiol molecules. The present study highlighted that activity of key enzymes involved in glucose metabolism is changed, owing to MeHg induced toxicity in the liver. Induction of similar toxic effects assumed to be stimulated by the production of high quantity free radicals.

Salient evidence testifies the link between organophosphorus (OPs) exposure and the formation of free radical oxidants; and it is well accepted that free radicals are one of the basic concerns of senescence. To show the oxidative features of phosalone (PLN) as a key member of OPs, to induce senescence in rat embryonic fibroblast (REF) cells and to demonstrate the beneficial effects of the known antioxidant ellagic acid (EA) in diminishing the PLN-induced toxic effects, the levels of cell viability, oxidative stress markers, inflammatory cytokines, telomerase activity, and the expression of the genes related to senescence were investigated. Our results lend support to the hypothesis that PLN enhances the entire premature senescence parameters of REF cells. This accounts for the mechanistic approval of the role of OPs in induction of senescence in rat fibroblasts. Moreover, incorporation of EA diminished PLN toxicity mainly through suppression of p38 and p53 at gene and protein levels, and tempered the inflammation factors (TNF-α, IL-1β, IL-6 and NF-κB), which further affected cell division. Analysis of cell cycle showed that the percentage of G0/G1 arrest, in REF cells treated by EA was elevated as compared to control and PLN treated cells.

Mercury (Hg) is a well-known heavy metal and causes various toxic effects. It is abundantly present in fish in the form of methyl mercury (MeHg). Also, various other forms of mercury can enter human body either from environment like inhalation or through dental amalgams. The present study was designed to assess MeHg induced toxicity in mouse plasma and pancreatic islets with respect to insulin secretion, oxidative balance, glucose tolerance, gene expression, caspases 3 and 9 activities. MeHg was dissolved in tap water and administered at doses 2.5, 5 and 10 mg/kg/day, for 4 weeks. In mice, MeHg significantly caused increase in plasma insulin as well as C-peptides. Glucose intolerance, insulin resistance and hyperglycemia are main consequences of our study that correlate with the gene expression changes of glucose homeostasis as well. MeHg caused increase lipid peroxidation in a dose-dependent manner in plasma as well as pancreatic islets. In addition, total thiol molecules and ferrous reducing antioxidant power in MeHg treated group was decreased in plasma as well as pancreatic islets. Caspases 3 and 9 activities of pancreatic islets were upregulated in MeHg exposed animals. Reactive oxygen species were extremely high in pancreatic islets of MeHg treated groups. MeHg disrupted gluconeogenesis/glycogenolysis pathways and insulin secretory functions of islets by targeting GDH, GLUT2 and GCK genes of pancreatic islets. In conclusion, the current study revealed that insulin pathways, oxidative balance and glucose metabolism encoded genetic makeup are susceptible to MeHg toxicity and the subsequent oxidative stress and alternations in gene expression could lead toward functional abnormalities in other organs.

This study evaluated the effects of Pistacia atlantica (P. atlantica), butyrate, Lactobacillus casei (L. casei) and especially their combination therapy on 2,4,6-trinitrobenzene sulphonic acid (TNBS)-induced rat colitis model. Rats were divided into seven groups. Four groups received oral P. atlantica, butyrate, L. casei and the combination of three agents for 10 consecutive days. The remaining groups were negative and positive controls and a sham group. Macroscopic and histopathological examinations were carried out along with determination of the specific biomarker of colonic oxidative stress, the myeloperoxidase (MPO). Compared with controls, the combination therapy exhibited a significant alleviation of colitis in terms of pathological scores and reduction of MPO activity (55%, p=0.0009). Meanwhile, the macroscopic appearance such as stool consistency, tissue and histopathological scores (edema, necrosis and neutrophil infiltration) were improved. Although single therapy by each P. atlantica, butyrate, and L. casei was partially beneficial in reduction of colon oxidative stress markers, the combination therapy was much more effective. In conclusion, the combination therapy was able to reduce the severity of colitis that is clear from biochemical markers. Future studies have to focus on clinical effects of this combination in management of human ulcerative colitis. Further molecular and signaling pathway studies will help to understand the mechanisms involved in the treatment of colitis and inflammatory diseases.

Genetic, environmental factors, dysregulation of immune system, intestinal microbes and oxidative stress are the most important factors that play the role in the pathogenesis of inflammatory bowel disease (IBD). Current treatments do not always result in complete remission and usually accompanied with several adverse effects. Recent studies showed that nuclear factor-kappa B (NF-κB), tumor necrosis factor-α (TNF-α) and oxidative stress play the pivotal role in the induction of inflammation. Butyrate, l -Carnitine, and probiotics have the potential to control inflammation by reduction of main inflammatory cytokines, including NF-κB and TNF-α. They also stimulate antioxidant enzymes and inhibit IκB kinase (IKK). Regarding the beneficial effects of these three compounds in inflammation via several mechanisms, we hypothesize that the mixture of these compounds would be synergistically effective in reduction of inflammation and alleviation of IBD. Further experimental investigations are needed, to evaluate the hypothesis.

AIM: To investigate the side effects of phosalone on intestinal cells and to evaluate benefits of ellagic acid (EA) as a remedy.METHODS: In order to conduct an in vivo study, a rat model was used. The rats were divided into ten groups based on the materials used in the experiment and their dosage. The first group was fed normally. The second group was administered EA through gavage. Next Four groups were given (1/3, 1/5, 1/10, 1/20) LD50 phosalone; an organophosphorus compound. The last four groups received (1/3, 1/5, 1/10, 1/20) LD50 phosalone and of EA. After one month, the rats were sacrificed and their colon cells were examined to evaluate the level of inflammation, proteins and oxidative stress markers.RESULTS: The results of this research show that phosalone elevates oxidative stress and changes the level of tumor necrosis factor-a (TNF-alpha), interlukin-6 beta (IL-6 beta) and nuclear factor (NF)-kappa b proteins. EA administration reduced phosalone toxicity and changed oxidative stress and inflammatory markers for all phosalone doses. Overall changes in reduction of TNF-alpha (230.47 +/- 16.55 pg/mg protein vs 546.43 +/- 45.24 pg/mg protein, P < 0.001), IL-6 beta (15.85 +/- 1.03 pg/mg protein vs 21.55 +/- 1.3 pg/mg protein, P < 0.05), and NF-kappa B (32.47 +/- 4.85 pg/mg protein vs 51.41 +/- 0.71 pg/mg protein, P < 0.05) manifest that the efficacy of EA is more viable for 1/3 LD50 dose of phosalone. Furthermore, EA is effective to counteract the negative outcomes of oxidative stress. When EA was used to treat 1/3 LD50 of phosalone's side effects, it improved the level of AChE activity (48.5% +/- 6% vs 25% +/- 7%, P < 0.05), TTM (0.391 +/- 0.008 mmol/L vs 0.249 +/- 0.032 mmol/L, P < 0.05), FRAP (46.04 +/- 5.005 mu mol/L vs 18.22 +/- 1.9 mu mol/L, P < 0.01) and MPO (0.222 +/- 0.019 U/mg protein vs 0.387 +/- 0.04 U/mg protein, P < 0.05).CONCLUSION: This research highlights that EA is effective to alleviate the side effects of phosalone by reducing the level of oxidative stress and inflammatory proteins.

Probiotics are live microorganisms, conferring a health benefit on the host when administered in a sufficient amount. Generally, Lactobacilli, Bifidobacteria, and Saccharomyces are recognized as “Generally Regarded As Safe by the WHO.” However, further caution is needed to administer probiotics to patients with compromised immune systems, leaky gut, or critical illnesses. Different strains of probiotics have different safety profiles, which should be taken into account, and generalizations in relation to all probiotics should be avoided. Particularly, the safety of probiotics in an at-risk population should be categorized as strain-by-strain basis, dose and interaction with other strains and pathologic conditions.

Tragopogon graminifolius DC. (Compositae) (TG) has been proposed as an efficacious remedy for gastrointestinal ulcers in Iranian traditional medicine.The present study evaluates the efficacy of TG on experimental colitis and the responsible mechanisms.After induction of IBD by 2,4,6-trinitrobenzenesulfonic acid (TNBS), rats received standardized ethanol extract of TG aerial part at 20, 30, or 50 mg/kg/d orally. After 12 d, the rats were sacrificed and the colon was removed and assessed for macroscopic and microscopic changes. Also, tumor necrosis factor-alpha (TNF-α), interleukin-1 beta (IL-1β), total antioxidant capacity, myeloperoxidase (MPO), and lipid peroxidation (LPO) were measured in the colon homogenate.TG extract significantly reduced macroscopic and microscopic scores of colitis with ED50 values of 23 and 39 mg/kg, respectively. MPO was significantly reduced in all plant extract groups with an ED50 value of 41 mg/kg. The ED50 values of extract for inhibition of TNF-α and LPO were 44 and 93 mg/kg, respectively. IL-1β significantly decreased by 50 mg/kg of TG extract (ED50 = 57 mg/kg). Total antioxidant power markedly increased by 50 mg/kg group (ED50 = 43 mg/kg).TG exhibited efficacy on TNBS-induced colitis via anti-inflammatory, immunomodulatory, antioxidant, and mucosal healing properties.TG possesses promising healing function on colitis. Clinical trials are warranted to prove its efficacy and tolerability in IBD.

Objective Organophosphorus (OP) compounds are used to control pests, however they can reach the food chain and enter the human body causing serious health problems by means of acetylcholinesterase (AChE) inhibition and oxidative stress (OS). Among the OPs, chlorpyrifos (CHP), malathion (MAL), and diazinon (DIA) are commonly used for commercial extermination purposes, in addition to veterinary practices, domestic, agricul- ture and public health applications. Two new recently registered medicines that contain selenium and other antioxidants, IMOD and angipars (ANG), have shown beneficial ef- fects for OS related disorders. This study examines the effect of selenium-based medi- cines on toxicity of three common OP compounds in erythrocytes. Materials and Methods In the present experimental study, we determined the ef- ficacy of IMOD and ANG on OS induced by three mentioned OP pesticides in human erythrocytes in vitro. After dose-response studies, AChE, lipid peroxidation (LPO), total antioxidant power (TAP) and total thiol molecules (TTM) were measured in eryth- rocytes after exposure to OPs alone and in combined treatment with IMOD or ANG. Results AChE activity, TAP and TTM reduced in erythrocytes exposed to CHP, MAL and DIA while they were restored in the presence of ANG and IMOD. ANG and IMOD reduced the OPs-induced elevation of LPO. Conclusion The present study shows the positive effects of IMOD and ANG in re- duction of OS and restoration of AChE inhibition induced by CHP, MAL and DIA in erythrocytes in vitro.

Background Coumarins are an important class of widely distributed heterocyclic natural products exhibiting a broad pharmacological profile. In this work, a new series of coumarins bearing substituted 3,4-dihydro-2H-benzothiazines were described as potential analgesic agents. The clinical use of NSAIDs as traditional analgesics is associated with side effects such as gastrointestinal lesions and nephrotoxicity. Therefore, the discovery of new safer drugs represents a challenging goal for such a research area. Results The target compounds 3-(3-methyl-3,4-dihydro-2H-benzo[b][1,4]thiazin-3-yl)-2H-chromen-2-ones 2a-u were synthesized and characterized by spectral data. The antinociceptive properties of target compounds were determined by formalin-induced test and acetic acid-induced writhing test in mice. Among the tested compounds, compound 2u bearing 2-(4-(methylsulfonyl)benzoyl)- moiety on benzothiazine ring and 4-(methylsulfonyl)phenacyloxy- group on the 7 position of coumarin nucleus showed better profile of antinocecieption in both models. It was more effective than mefenamic acid during the late phase of formalin-induced test as well as in the acetic acid-induced writhing test. Conclusion Considering the significant antinoceciptive action of phenacyloxycoumarin derivatives, compound 2u prototype might be further used as model to obtain new more potent analgesic drugs.

To investigate the beneficial effect of the combination of butyrate, Lactobacillus casei, and L-carnitine in a rat colitis model.Rats were divided into seven groups. Four groups received oral butyrate, L-carnitine, Lactobacillus casei and the combination of three agents for 10 consecutive days. The remaining groups included negative and positive controls and a sham group. Macroscopic, histopathological examinations, and biomarkers such as tumor necrosis factor-alpha (TNF-α) and interlukin-1β (IL-1β), myeloperoxidase (MPO), thiobarbituric acid reactive substances (TBARS), and ferric reduced ability of plasma (FRAP) were determined in the colon.The combination therapy exhibited a significant beneficial effect in alleviation of colitis compared to controls. Overall changes in reduction of TNF-α (114.66 ± 18.26 vs 171.78 ± 9.48 pg/mg protein, P0.05), IL-1β (24.9 ± 1.07 vs 33.06 ± 2.16 pg/mg protein, P0.05), TBARS (0.2 ± 0.03 vs 0.49 ± 0.04 μg/mg protein, P0.01), MPO (15.32 ± 0.4 vs 27.24 ± 3.84 U/mg protein, P0.05), and elevation of FRAP (23.46 ± 1.2 vs 15.02 ± 2.37 μmol/L, P0.05) support the preference of the combination therapy in comparison to controls. Although the monotherapies were also effective in improvement of colitis markers, the combination therapy was much better in improvement of colon oxidative stress markers including FRAP, TBARS, and MPO.The present combination is a suitable mixture in control of experimental colitis and should be trialed in the clinical setting.