[Show abstract][Hide abstract] ABSTRACT: Inflammatory bowel disease (IBD) is a chronic condition of the intestine with unknown etiology involving multiple immune, genetic and environmental factors. We were interested to examine the effect of total extract from Zataria multiflora Boiss, a folk medicinal plant on prevention and treatment of experimental IBD. Z. multiflora was administered (400, 600, 900 p.p.m.) through drinking water to IBD mice induced by intrarectal administration of acetic acid. Prednisolone was used as the standard drug for comparison. Biochemical, macroscopic and microscopic examinations of colon were performed. Biochemical evaluation of inflamed colon was done using assay of myeloperoxidase (MPO) activity and thiobarbituric acid reactive substances (TBARS) concentration as indicators of free radical activity and cell lipid peroxidation. The activity of MPO and lipid peroxidation products (TBARS) increased in acetic acid-treated groups while recovered by pretreatment of animals with Z. multiflora (400-900 p.p.m.) and prednisolone. Z. multiflora (600 and 900 p.p.m.) and prednisolone-treated groups showed significantly lower score values of macroscopic and microscopic characters when compared with the acetic acid-treated group. The beneficial effect of Z. multiflora (900 p.p.m.) was comparable with that of prednisolone. The antioxidant, antimicrobial and anti-inflammatory potentials of Z. multiflora might be the mechanisms by which this herbal extract protects animals against experimentally induced IBD. Proper clinical investigation should be carried out to confirm the activity in human.
Evidence-based Complementary and Alternative Medicine 04/2007; 4(1):43-50. DOI:10.1093/ecam/nel051 · 1.88 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Growth factors and nitric oxide (NO) play a major role in dysregulated immune response in ulcerative colitis (UC). Recent evidence has shown increased levels of transforming growth factor-beta(1) (TGF-beta(1)) in UC and suggested an anti-inflammatory effect for this factor. Based on our recent study, dysfunctional immunoregulation is present in saliva of UC patients, we hypothesized that salivary level of NO and TGF-beta(1) may differ by severity of UC and be useful to determine the activity of the disease. Thirty-seven UC patients and 15 healthy controls were enrolled and saliva samples were obtained. Truelove-Witts severity index and modified Truelove-Witts severity index were used to determine the severity of the disease. NO and TGF-beta(1) levels were detected in saliva of all patients and control subjects using enzyme-linked immunosorbent assay. A total of 21 patients had mild disease while 8 had moderate and 8 had severe colitis. Adjusted for baseline characteristics, the levels of NO and TGF-beta(1) in different groups were compared. Salivary NO and TGF-beta(1) levels were higher in UC patients comparing to controls (P < 0.00005 and P = 0.005, respectively). The levels of NO and TGF-beta(1) showed no significant differences among the severity groups (P = 0.46 and P = 0.23, respectively). NO levels linearly increased by age (Coeff = 1.5, r = 0.38, P = 0.02). Gender, extension of disease, and medical treatment did not affect NO and TGF-beta(1) levels. Although UC patients have abnormal amounts of NO and TGF-beta(1) in their saliva, their disease activity cannot be predicted by these factors, which may indicate a pathophysiologic role rather than being nonspecific inflammatory markers for TGF-beta(1) and NO.
Annals of the New York Academy of Sciences 01/2007; 1095(1):305-14. DOI:10.1196/annals.1397.034 · 4.38 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: It has been postulated that oxidative stress, nitric oxide (NO), and transforming growth factor beta(1) (TGF- beta(1)) have major roles in the pathophysiology of Crohn's disease (CD). The aim of this study was to determine the salivary levels of total antioxidant capacity (TAC), specific antioxidants (i.e., uric acid, albumin, transferrin, and thiol molecules), lipid peroxidation (LPO), NO, and TGF- beta(1) in CD patients and control subjects and to also investigate their correlation with activity of the disease. Twenty-eight patients with confirmed diagnosis of CD were enrolled and whole saliva samples were obtained. Smokers, diabetics, those who suffered from periodontitis, and those who were consuming antioxidant supplements were excluded from the study. The Crohn's Disease Activity Index (CDAI) was used to determine the severity of the disease. Twenty healthy subjects were also recruited. In CD patients significant reductions in salivary levels of TAC (0.248 +/- 0.145 vs. 0.342 +/- 0.110 mmol/L), albumin (1.79 +/- 0.42 vs. 2.3 +/- 0.2 microg/mL), and uric acid (3.1 +/- 1.4 vs. 4.1 +/- 2.0 mg/dL) were found. TGF-beta(1) was significantly increased in CD patients compared to healthy subjects (3.02 +/- 1.54 vs. 2.36 +/- 0.52 ng/mL). A fourfold increase in NO levels (198.8 +/- 39.9 vs. 50.2 +/- 21.3 micromol/L) along with a fivefold increase in LPO concentration (0.146 +/- 0.064 vs. 0.027 +/- 0.019 micromol/L) was documented in CD patients in comparison to the control group. CDAI significantly correlated with the TAC, LPO, and the interaction between TAC and LPO (r(2) = 0.625, r(2) = 0.8, F-test's P < 0.00005). Saliva of CD patients exhibits an abnormal feature with respect to oxidative stress, NO, and TGF-beta(1). TAC and LPO modify the effect of each other in determination of CD severity, which underlines the importance of oxidative stress in the pathogenesis of CD.
Annals of the New York Academy of Sciences 12/2006; 1091(1):110-22. DOI:10.1196/annals.1378.060 · 4.38 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Inflammatory bowel disease (IBD) is a chronic condition of the intestine with unknown etiology involving multiple immune, genetic and environmental factors. We were interested in examining the effect of a total extract from Ziziphora clinopoides, an Iranian folk herbal medicine, in the prevention and control of experimental mouse IBD. Z. clinopoides was administered (75, 150, 300 mg/kg) through drinking water to mice, which dispensed a toxic dose of acetic acid intrarectally. Prednisolone was used as the standard drug for comparison. Biochemical, macroscopic and microscopic examinations of the colon were performed. Biochemical evaluation of the inflamed colon was carried out using assays of myeloperoxidase (MPO) activity and thiobarbituric acid reacting substances (TBARS) as indicators of free radical activity and cellular lipid peroxidation. Results indicated that the activity of MPO and lipid peroxidation products (TBARS) increased in acetic acid-treated groups, while recovered by pretreatment of animals with Z. clinopoides (75-300 mg/kg) and prednisolone. All doses of Z. clinopoides and prednisolone-treated groups showed significant lower score values of macroscopic and microscopic characters when compared to the acetic acid-treated group. The beneficial effect of Z. clinopoides (300 mg/kg) was comparable to that of prednisolone. It is concluded that Z. clinopoides inhibits acetic acid toxic reactions in the mouse bowel through inhibition of cellular oxidative stress. Proper clinical investigation should be carried out to confirm the same activity in human.
[Show abstract][Hide abstract] ABSTRACT: A series of azolylchroman derivatives were prepared as conformationally constrained analogs of (arylalkyl)azole anticonvulsants. The anticonvulsant activities of the compounds were evaluated by determining seizure latency and protective effect against pentylenetetrazole (PTZ)-induced lethal convulsions in mice at a dose of 5mg/kg. Among these compounds, 7-chloro-3-(1H-imidazol-1-yl)chroman-4-one and 3-(1H-1,2,4-triazol-1-yl)chroman-4-one exhibited significant action in delaying seizures as well as effective protection against PTZ-induced seizures and deaths.
[Show abstract][Hide abstract] ABSTRACT: Background: Acute brain injury (ABI) disrupts homeostasis in tissue brain. Inflammation has an important contributory role in the pathogenesis of the disease and blood cell count alteration has been shown. The clinical course is variable, and the factors or markers available for predicting survival or the functional situation of these patients are limited. Aim: The aim of this study was to measure the serum levels of interleukin (IL)-8, transforming growth factor (TGF)-β1 and nitric oxide (NO) in patients with ABI (at days 1, 2, 3 and 7) and to study their relationships to blood cell counts. Methods & results: A total of 25 patients were included in the study and 15 healthy subjects were chosen as a control group. Expression of IL-8 and TGF-β1 and production of NO were higher in ABI patients at each of the time points as compared with the control group. In the case of TGF-β1, the increase at time points 3 and 7 was greater than time points 1 and 2. White blood cells were increased significantly (12130 ± 1372 cells/μl; p < 0.01). A huge decrease in platelet counts was also observed (202 ± 14 cells/μl; p < 0.01). Interestingly, no significant correlation was found between the serum levels of these mediators and blood cell counts (mainly considered leukocytes and platelets). Discussion & conclusion: This study shows dramatic increase in the serum levels of three important mediators involved in inflammation and progression of ABI. We showed that there is no correlation between the serum levels of these mediators, leukocytes and platelets and probably they act independently from each other.
[Show abstract][Hide abstract] ABSTRACT: The objective of the present study was to evaluate the anti-inflammatory and analgesic activities of the crude and fractioned extracts (ether, ethyl acetate, n -butanol and water) of Phlomis anisodonta (Lamiaceae) in the models of carrageena n -induced paw edema and acetic acid-induced writhing in mice. Dried powdered material from the aerial parts of Phlomis anisodonta was extracted with methanol (80%) twice. The methanol extract was separated into four fractions: after drying the methanol extract, the solid residue was dissolved in water and the water-soluble portion was successively partitioned to produce the above-mentioned fractions. The total extract, ether fraction and ethyl acetate fractions significantly reduced the number of writhings compared to the control group. Water and n -butanol fractions showed no analgesic activity. Neither the total extract nor four fractions were more effective than indomethacin in acetic acid-induced test. In carrageena n -induced inflammation test, only water and ethyl acetate fractions showed antiinflammatory activity compared to the control group. The total extract, n -butanol and ether fractions showed no antiinflammatory activity. Neither the total extract nor four fractions were more effective than indomethacin. Different types of glycosides found in the genus Phlomis could be responsible for observed effects. Variations in antiinflammatory and analgesic effects of different fractions of this plant might be attributed to the fact that different fractions of P. anisodonta contain active compounds in variable ratios and activities. A comprehensive analysis for determination and quantification of these compounds is required).
International Journal of Pharmacology 02/2006; 2(2). DOI:10.3923/ijp.2006.209.212 · 0.71 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The purpose of this investigation was to study the anti-inflammatory and analgesic properties of total extract and four fractions (ether, ethyl acetate, n-butanol and water) from Phlomis lanceolata (Lamiaceae) in mice. The plant material was extracted with methanol. In order to estimate the polarity of the active compounds, the total extract was dissolved in water and the water soluble portion was successively partitioned between ether, ethyl acetate and n -buthanol. The total extract and four fractions were analyzed by Thin Layer Chromatography (TLC) by use of specific reagents. Dose of 100 mg kg <sup>1</sup> of each extracts were used in carrageenan-induced paw edema, formalin and writhing nociception tests in mice. All compounds reduced paw edema in comparison to the control group at 1, 3, 5 and 7 h post carrageenan injection. The total, ether and aqueous extracts were similar to indomethacin while the ethyl acetate extract was weaker than indomethacin in reduction of paw edema. All extracts induced antinociception in both phases of formalin test. The total and ether extracts were as potent as indomethacin in both phases of formalin test. The ethyl acetate extract was weaker than indomethacin in the second phase of formalin-test while the n -butanol and aqueous extracts showed more antinociception than indomethacin in the second phase of formalin test. All extracts as well as indomethacin induced antinociception in writhing test in comparison to control. The total and aqueous extracts induced the same antinociception as indomethacin while ether, ethyl acetate and n -butanol showed weaker antinociception than indomethacin. Positive results for iridoids and phenolic compounds were indicated by phytochemical analysis of total extract. Phenolic compounds were found in four fractions whereas only n -butanol and aqueous fractions showed positive results for iridoid glycosides. The higher antinociceptive effects of n -butanol and aqueous extracts in the inflammatory phase of formalin test among different extracts tested, might back to the presence of iridoid glycosides, phenolic glycosides or other glycosides. These data suggest that different extracts of P. lanceolata produce different antinociceptive activities that could be due to the effect of one or a combination of the bioactive components in each extract.
International Journal of Pharmacology 01/2006; 2(1). DOI:10.3923/ijp.2006.50.54 · 0.71 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Experimental findings suggest a protective role for cyclic nucleotides against induction of oxidative stress in saliva. Oxidative stress is a major contributor to the pathogenesis of inflammatory diseases. This study was conducted to evaluate salivary oxidative stress along with cGMP and cAMP levels in periodontitis subjects. cAMP and cGMP are second messengers that have important roles in salivary gland functions. Unstimulated whole saliva samples were obtained from periodontitis patients and age- and sex-matched healthy individuals. Saliva samples were analyzed for thiobarbituric reactive substances (TBARS) as a marker of lipid peroxidation, ferric reducing ability (total antioxidant power, TAP), and levels of cAMP and cGMP. Concentrations of cAMP and cGMP were reduced in the saliva of patients with moderate and severe periodontitis. Saliva of patients with severe periodontitis had higher TBARS and lower TAP than control subjects. The presence of oxidative stress and lower levels of salivary cGMP and cAMP in periodontitis are in association with disease severity.
The journal of contemporary dental practice 12/2005; 6(4):46-53.
[Show abstract][Hide abstract] ABSTRACT: The aim of this study was to examine how type 1 diabetic patients have altered levels of lipid peroxidation, antioxidant defense, NO and EGF in their plasma and saliva. We tested the differences in lipid peroxidation level, antioxidant power, and concentrations of epidermal growth factor (EGF) and nitric oxide (NO) in saliva and blood of type 1 diabetic subjects in comparison to healthy control subjects.
Nineteen subjects with type 1 diabetes mellitus and 19 healthy age- and sex-matched control subjects were included in the study. Blood and saliva samples were obtained and analyzed for thiobarbituric reactive substances (TBARS) as a marker of lipid peroxidation, ferric reducing ability (total antioxidant power), EGF and NO levels.
TBARS levels did not show a significant difference between the two groups. Analysis of antioxidant power revealed that saliva and plasma of diabetic patients had more antioxidant power (p <0.01) than the healthy control population (107 +/- 10.35 vs. 11.14 +/- 4.66 and 192 +/- 12.3 vs. 142 +/- 15.2 mmol/L, respectively). Concentration of EGF was increased (p <0.01) in saliva whereas it was reduced (p <0.01) in plasma of diabetic patients in comparison to those of healthy subjects (2423 +/- 322 vs. 1513 +/- 341 and 125 +/- 14 vs. 346 +/- 60 pg/mL, respectively). NO level increased in both saliva and plasma of diabetic patients in comparison to those of healthy subjects (46.61 +/- 7 vs. 72.89 +/- 13 and 62.11 +/- 4.6 vs. 76.25 +/- 5 micromol/L, respectively). Blood HbA1c (%) of patients was significantly higher than that of controls (8.3 +/- 0.32 vs. 5.4 +/- 0.24, p <0.01).
Existence of increased total antioxidant power in the presence of normal lipid peroxidation in plasma and saliva of type 1 diabetic patients indicates the existence of oxidative stress. Increased salivary EGF and NO levels in association with elevated TAOP is interesting and should be further studied.
Archives of Medical Research 07/2005; 36(4):376-81. DOI:10.1016/j.arcmed.2005.03.007 · 2.65 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Excessive production of reactive oxygen species has been observed following acute and chronic exposure to radiation in animal models which can lead to several detrimental and irreversible outcomes in vital organs. Aim of this study was to determine the oxidative stress status in radiology unit workers which are exposed to persistent low-dose radiation. METHODS:: A group of 32 radiology unit employees along with 32 sex- and age-matched hospital workers, not exposed to low-dose radiation were recruited from two separate hospitals for the study. Exposed subjects showed higher levels of lipid peroxidation (P=0.009), total antioxidant capacity (P=0.0006) and thiol groups (P=0.03). It is concluded that occupationally exposed individuals are oxidatively stressed and precautions such as antioxidant therapy seems reasonable.
[Show abstract][Hide abstract] ABSTRACT: Benzodiazepines (BZDs) are the most commonly prescribed hypnotic-anexiolytic-sedative drugs in the world. Their effectiveness and safe usage have made them extremely popular among patients. To date more than 30 different brands of BZDs have been introduced to drug market, which vary enormously in side effects, potency and indications. Thus, due to global consumption and diversity of BZDs, lack of a information indicating the BZDs` side effects sorted by induced signs and symptoms, this study would ease the consultation and follow-up of the patients who have undergone BZD treatment. The review first gives a brief introduction about side effects encountered by BZDs and then classifies the signs and symptoms based on the organ involved and mentions which BZDs are responsible for them. The organs and functions which are influenced are classified under: cardiovascular system, CNS, cognitive function, mood changes, endocrine/metabolic, gastrointestinal tract, blood and bone marrow, liver, eyes, respiratory system, skin, genitourinary tract, musculoskeletal system, ears and miscellaneous. Each of these items is also sub-grouped into several categories.
International Journal of Pharmacology 04/2005; DOI:10.3923/ijp.2005.376.382 · 0.71 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Background: Irritable bowel syndrome (IBS) is a disorder with unknown pathophysiology, although it would appear that stress of different types plays an important role in the onset and development of the disorder. It affects 10-15% of the general population. Currently, anticholinergics and prokinetics are the main therapies. Objective: The objective of this study was to examine the effects of sildenafil in an animal model of IBS. Methods: IBS was induced in rats using the wrap-restraint method and sildenafil was administered intragastrically by gavage at doses of 0.5, 1 and 5 mg/kg. Gastric emptying, small bowel transit and fecal excretion (index of large intestine motility) as well as concentrations of cyclic nucleotides (cGMP and cAMP) and total antioxidant capacity in the large intestine were determined. Results: Sildenafil at all doses used (0.5, 1 and 5 mg/kg) significantly reduced gastric emptying up to 120 min postdrug administration. All doses (0.5, 1 and 5 mg/kg) of sildenafil dose-dependently reduced small bowel transit up to 60 and 90 min after sildenafil administration. Treatment of rats using sildenafil (0.5, 1 and 5 mg/kg) increased the concentration of cAMP 40 min post administration. At 90 min postdrug administration, only sildenafil (5 mg/kg) increased cAMP concentration. At 40 min postdrug administration, sildenafil (1 and 5 mg/kg) and at 90 min, all doses of sildenafil increased the concentration of cGMP. Sildenafil (5 mg/kg) increased total antioxidant capacity and reduced fecal excrements in IBS rats. Conclusion: Sildenafil administration appears to have beneficial effects in the treatment of IBS in rats, which is in relation with the drugs potential to increase bowel total antioxidant capacity and cyclic nucleotides.
[Show abstract][Hide abstract] ABSTRACT: A series of N-Arylhydrazone derivatives of mefenamic acid (a known non-steroidal anti-inflammatory drug) were synthesized in order to obtain new compounds with potential analgesic and anti-inflammatory activity.
The structures of all synthesized compounds were confirmed by means of infrared, proton magnetic resonance and mass spectroscopy. All compounds were evaluated for their analgesic and anti-inflammatory activities by abdominal constriction test (writhing test) and carrageenan-induced rat paw edema test respectively.
Most of the synthesized compounds induced significant reduction in the writhing response when compared to control. Among them, compounds 11, 12, 15, 16, 19, 20, and 21 were significantly more potent than mefenamic acid in the writhing test. The anti-inflammatory activity of these 7 compounds were evaluated and compounds 11, 12, 16, 19 and 20 showed significant anti-inflammatory activity in comparison to control but their effect was weaker than mefenamic acid.
The antinociceptive relative activity of some of these newly synthesized compounds is greater than mefenamic acid but they are not potent anti-inflammatory agents.
Journal of Pharmacy and Pharmaceutical Sciences 02/2005; 8(3):419-25. · 1.86 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Increased oxidative stress has been suggested to be involved in the pathogenesis and progression of diabetic tissue damage. The aim of this study was to investigate the effect of different phosphodiesterase inhibitors on lipid peroxidation and total antioxidant capacity (TAC) of plasma in streptozotocin-induced diabetic rats (Rattus norvegicus). Rats became diabetic by a single administration of streptozotocin (STZ, 45 mg/kg). The effects of 15-days treatment by milrinone, sildenafil, and theophylline as cyclic-AMP and -GMP phosphodiesterase inhibitors (PDEIs) on diabetes-induced oxidative stress were studied. The levels of glucose, malonedialdehyde (MDA) the by product of lipid peroxides, and TAC (FRAP test) were estimated in plasma of control and experimental groups of rats. A significant increase in the levels of plasma glucose, and MDA and a concomitant decrease in the levels of TAC were observed in diabetic rats. These alterations were reverted back to near normal level after the treatment with PDEIs. Treatment of diabetic rats by PDEIs reduced MDA levels and increased TAC in the order of milrinone>sildenafil>theophylline. In conclusion, the present investigation show that PDIS possesses antioxidant activities, which may be attributed to their enhancing effect on cellular cyclic nucleotides contributing to the protection against oxidative stress in streptozotocin-induced diabetes. Exact mechanism of protective actions of cAMP- and cGMP-phosphodiesterase remains to be elucidated by further studies. This finding may suggest a place for PDEIs in maintaining health in diabetes.
Comparative Biochemistry and Physiology Part C Toxicology & Pharmacology 02/2005; 140(2):251-5. DOI:10.1016/j.cca.2005.02.010 · 2.30 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The objective of this randomized, double-blind placebo-controlled clinical trial was to evaluate the value of allopurinol treatment on reduction of oxidative stress in patients with diabetes type II patients. Forty-one diabetic type II subjects were randomly assigned to two groups. One group (n = 20) received 100 mg allopurinol three times a day for 14 days and the other group (n = 21) received a placebo. Blood and saliva samples were collected before and after intervention for analysis of lipid peroxidation level and total antioxidant power as indices of oxidative stress. At the beginning of the study, the groups were similar based upon age, duration of diabetes, fasting glucose, and HbA1c. Both allopurinol and placebo were effective in reduction of lipid peroxidation and total antioxidant power whether in saliva or plasma in a similar extent. HbA1c and FBS levels did not change through the study neither in case or placebo group. It is concluded that allopurinol therapy is not more effective than placebo in reduction of oxidative stress in diabetic patients. The same trend of changes in blood and saliva shown for oxidative stress indices was interesting and suggests a chance for saliva to be valuable in diagnosis of oxidative stress. However, to elaborate the exact role of allopurinol in diabetes, further large randomized clinical trials are needed.