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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. [ABSTRACT FROM AUTHOR]

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, agriculture and public health applications. Two new recently registered medicines that contain selenium and other antioxidants, IMOD and angipars (ANG), have shown beneficial effects for OS related disorders. This study examines the effect of selenium-based medicines on toxicity of three common OP compounds in erythrocytes. Materials and Methods: In the present experimental study, we determined the efficacy 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 erythrocytes 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 reduction of OS and restoration of AChE inhibition induced by CHP, MAL and DIA in erythrocytes in vitro. [ABSTRACT FROM AUTHOR]

Context: Tragopogon graminifolius DC. (Compositae) (TG) has been proposed as an efficacious remedy for gastrointestinal ulcers in Iranian traditional medicine. Objective: The present study evaluates the efficacy of TG on experimental colitis and the responsible mechanisms. Materials and methods: 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. Result: 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). Discussion: TG exhibited efficacy on TNBS-induced colitis via anti-inflammatory, immunomodulatory, antioxidant, and mucosal healing properties. Conclusion: TG possesses promising healing function on colitis. Clinical trials are warranted to prove its efficacy and tolerability in IBD. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

The uses of non-steroidal anti-inflammatory drugs (NSAIDs) are limited by a variety of side effects. So research on preparing new analgesic agents is important. According to some reports about the analgesic activity of hydrazide and hydrazine derivatives a new series of these compounds were synthesized in order to obtain new analgesic compounds. The final compounds 10a-10e and 15a-15d were prepared by condensation of corresponding hydrazides 7,8 and 11-14 with different aldehydes 9a-9e. The structures of all synthesized compounds were confirmed by means of FT-IR, ¹H-NMR and Mass spectra. All compounds were evaluated for their analgesic activities by abdominal constriction test (writhing test). Most of the synthesized compounds induced significant reduction in the writhing response when compared to control and compound 15 was more potent than mefenamic acid in the writhing test. [ABSTRACT FROM AUTHOR]

The present study was designed to determine the effect of a new 25Mg2+-carrying nanoparticle (25MgPMC16) on energy depletion, oxidative stress, and electrocardiographic (ECG) parameters on heart tissue of the rats poisoned by aluminum phosphide (AlP). 25MgPMC16 at doses of 0.025, 0.05, and 0.1 median lethal dose (LD50 = 896 mg/kg) was administered intravenously (iv) 30 min after a single intragastric administration of AlP (0.25 LD50). Sodium bicarbonate (Bicarb; 2 mEq/kg, iv) was used as the standard therapy. After anesthesia, the animals were rapidly connected to an electronic cardiovascular monitoring device for monitoring of ECG, blood pressure (BP), and heart rate (HR). Later lipid peroxidation, antioxidant power, ATP/ADP ratio, and Mg concentration in the heart were evaluated. Results indicated that after AlP administration, BP and HR decreased while R-R duration increased. 25MgPMC16 significantly increased the BP and HR at all doses used. We found a considerable increase in antioxidant power, Mg level in the plasma and the heart and a reduction in lipid peroxidation and ADP/ATP ratio at various doses of 25MgPMC16, but 25MgPMC16-0.025 + Bicarb was the most effective combination therapy. The results of this study support that 25MgPMC16 can increase heart energy by active transport of Mg inside the cardiac cells.25MgPMC16 seems ameliorating AlP-induced toxicity and cardiac failure necessitating further studies. [ABSTRACT FROM AUTHOR]