Hamit Hakan Alp

Antiulcer activity of fluvoxamine in rats and its effect on oxidant and antioxidant parameters in stomach tissue

BackgroundAlthough many drugs are available for the treatment of gastric ulcers, often these drugs are ineffective. Many antidepressant drugs have been shown to have antiulcer activity in various models of experimental ulcer. One such drug, the antidepressant mirtazapine, has been reported to have an antiulcer effect that involves an increase in antioxidant, and a decrease in oxidant, parameters. To date, however, there is no information available regarding the antiulcer activity for a similar antidepressant, fluvoxamine. This study aimed to investigate the antiulcer effects of fluvoxamine and to determine its relationship with antioxidants.MethodsGroups of rats fasted for 24 h received fluvoxamine (25, 50, 100 and 200 mg/kg), ranitidine (50 mg/kg) or distilled water by oral gavage. Indomethacin (25 mg/kg) was orally administered to the rats as an ulcerative agent. Six hours after ulcer induction, the stomachs of the rats were excised and an ulcer index determined. Separate groups of rats were treated with the same doses of fluvoxamine and ranitidine, but not with indomethacin, to test effects of these drugs alone on biochemical parameters. The stomachs were evaluated biochemically to determine oxidant and antioxidant parameters. We used one-way ANOVA and least significant difference (LSD) options for data analysis.ResultsThe 25, 50, 100 and 200 mg/kg doses of fluvoxamine exerted antiulcer effects of 48.5, 67.5, 82.1 and 96.1%, respectively, compared to the control rat group. Ranitidine showed an 86.5% antiulcer effect. No differences were observed in the absence of indomethacin treatment for any dose of fluvoxamine or for ranitidine. The levels of antioxidant parameters, total glutathione and nitric oxide, were increased in all fluvoxamine groups and in the ranitidine group when compared with the indomethacin-only group. In addition, fluvoxamine and ranitidine decreased the levels of the oxidant parameters, myeloperoxidase and malondialdeyhyde, in the stomach tissues of the rats when compared to indomethacin group.ConclusionWe conclude that fluvoxamine has antiulcer effects, and that these occur by a mechanism that involves activation of antioxidant parameters and inhibition of some toxic oxidant parameters.

Adaptation of rat gastric tissue against indomethacin toxicity.

Indomethacin is used in the treatment of inflammatory diseases. But the drug toxicity limits its usage. This study investigated whether adaptation occurred after various dosages of repeated (chronic) indomethacin in rats to the gastro-toxic effects of indomethacin. It also examined whether the adaptation was related to oxidant-antioxidant mechanisms and oxidative DNA damage in gastric tissue. To illuminate the adaptation mechanism in the gastric tissue of rats given various dosages of chronic indomethacin, the levels of oxidants and antioxidants (GSH, MDA, NO, SOD and MPO), activities of COX-1 and COX-2 enzymes and oxidative DNA damage (8-OHd Gua/10(5) Gua) were measured. Results were compared to 25-mg/kg single-dose indomethacin group, and the role of oxidant and antioxidant parameters and oxidative DNA damage in the adaptation mechanism was evaluated. The average ulcer areas of gastric tissue of the 0.5-, 1-, 2-, 3-, 4-, and 5-mg/kg dosages of chronic indomethacin given to rats were 19.5+/-3.7, 12.5+/-3.3, 10+/-5.2, 4.5+/-3.6, 8.6+/-2.4, and 9.5+/-2.1mm(2), respectively. This rate was measured as 21.3+/-2.6mm(2) in the single-dose indomethacin group. Consequently, after various dosages of repeated (chronic) indomethacin administration in rats, it was observed that a clear adaptation developed against gastric damage and that gastric damage was reduced. The best adaptation was observed in the gastric tissue of the 3-mg/kg chronic indomethacin group. In parallel with the damage reduction, the oxidant parameters (MDA and MPO) and oxidative DNA damage (8-OHd Gua/10(5) Gua) were reduced, and the antioxidant parameters (GSH, NO and SOD) were increased. There is no relation between COX enzymes and adaptation mechanism. This circumstance shows that not COX-1 and COX-2 enzymes, oxidant and antioxidant parameters may play a role in the adaptation mechanism.

Effect of acute and chronic administration of progesterone, estrogen, FSH and LH on oxidant and antioxidant parameters in rat gastric tissue

This study was conducted to investigate whether gastro-protective and gastro-toxic effects of acute and chronic administration of progesterone, estrogen, FSH and LH were related to oxidant and antioxidant parameters. Chronic administration of progesterone at a low dose (1mg/kg), which probably could not stimulate progesterone receptors (PRs), inhibited oxidative stress of FSH in gastric tissue by suppressing FSH. Progesterone (5mg/kg) may have been caused oxidative stress as reflected by PR stimulation. FSH may have decreased antioxidant parameters and increased oxidant parameters via PRs. Chronic administration of low dose of estrogen (1mg/kg) inhibited LH and but could not stimulate alpha-2 adrenergic receptors, which resulted in oxidative stress in gastric tissue. The higher dose of estrogen (5mg/kg), however, could stimulate alpha-2 receptors, exhibited antioxidant activity in acute and chronic administration. While antioxidant activity of estrogen and LH was blocked with yohimbine (an alpha-2 adrenergic receptor blocker), mifepristone prevented the oxidative stress of progesterone and FSH in gastric tissue. It is concluded that low doses of progesterone may inhibit FSH, whereas high doses of estrogen may stimulate alpha-2 receptors, suggesting that LH could have protective and antioxidant hormone effects.

Oxidative DNA damage correlates with carotid artery atherosclerosis in hemodialysis patients.

Oxidative stress is accepted as a nonclassical cardiovascular risk factor in chronic renal failure patients. The aim of this study was to evaluate the relation between oxidative DNA damage (8‐hydroxy‐2′‐deoxyguanosine/deoxyguanosine [8‐OHdG/dG] ratio), oxidative stress biomarkers, antioxidant enzymes, and carotid artery intima‐media thickness (CIMT) in hemodialysis (HD) patients. Forty chronic HD patients without known atherosclerotic disease and 48 age‐ and sex‐matched healthy individuals were included in the study. Plasma malondialdehyde (MDA) levels and 8‐OHdG/dG ratio were determined as oxidative stress markers. Superoxide dismutase (SOD) and glutathione peroxidase (GPx) activities were measured as antioxidants. CIMT was assessed by carotid artery ultrasonography. 8‐OHdG/dG ratios and MDA levels were higher; SOD and GPx activities were lower in HD patients compared to controls. HD patients had significantly higher CIMT compared to controls (0.61 ± 0.08 vs. 0.42 ± 0.05, p < 0.001). There was a significant positive correlation between CIMT and 8‐OHdG/dG ratio (r = 0.57, p < 0.01) and MDA levels (r = 0.41, p < 0.01), while there was a significant negative correlation between CIMT and SOD (r = −0.47, p < 0.01) and GPx levels (r = −0.62, p < 0.01). It is firstly demonstrated that CIMT is positively correlated with oxidative DNA damage in HD patients without known atherosclerotic disease.

Vitamin E and Hippophea rhamnoides L. extract reduce nicotine-induced oxidative stress in rat heart

The effects of vitamin E and Hippophea rhamnoides L. extract (HRe‐1) on nicotine‐induced oxidative stress in rat heart were investigated. There were eight rats per group and supplementation period was 3 weeks. The groups were: nicotine [0.5 mg kg−1day−1, intraperitoneal (i.p.)]; nicotine plus vitamin E [75 mg kg−1day−1, intragastric (i.g.)]; nicotine plus HRe‐1 (250 mg kg−1day−1, i.g.); and the control group (receiving only vehicles). Nicotine increased the malondialdehyde level, which was prevented by both vitamin E and HRe‐1. Glutathione peroxidase (GPx) activity in nicotine plus vitamin E supplemented group was higher than the others. Glutathione S‐transferase (GST) activity in nicotine plus HRe‐1 supplemented group was increased compared with the control group. Catalase activity was higher in nicotine group compared with others. GPx activity in nicotine plus vitamin E supplemented group was elevated compared with the others. Total and non‐enzymatic superoxide scavenger activities in nicotine plus vitamin E supplemented group were lower than nicotine plus HRe‐1 supplemented group. Superoxide dismutase (SOD) activity was higher in nicotine plus HRe‐1 supplemented group compared with others. Glutathione reductase activity and nitric oxide level were not affected. Increased SOD and GST activities might have taken part in the prevention of nicotine‐induced oxidative stress in HRe‐1 supplemented group in rat heart. Flavonols such as quercetin, and isorahmnetin, tocopherols such as α‐tocopherol and β‐tocopherol and carotenoids such as α‐carotene and β‐carotene, reported to be present in H. rhamnoides L. extracts may be responsible for the antioxidant effects of this plant extract. Copyright

Reason for the aggravation of diseases caused by inflammation and the ineffectiveness of NSAIDs on these diseases in rainy weather

In this study, the anti-inflammatory activity of indomethacin, diclofenac, meloxicam and nimesulide were investigated on sunny and rainy days. Parallel to these experiments, the question of whether endogenous adrenaline and cortisol (corticosterone in rats) are factors that affect medicinal activity of these anti-inflammatory drugs on sunny and rainy days was examined. Our experimental results show that the drugs used produced significant anti-inflammatory effects on sunny days (76.5, 62.8, 56.9 and 64.7%, respectively) but were less effective on rainy days. On sunny days, adrenaline levels decreased by 83-86% in the groups that received indomethacin, diclofenac, meloxicam or nimesulide, compared to the control group. In contrast, there was no significant difference in corticosterone levels in any of these groups. In addition, the adrenaline and corticosterone levels of intact (versus adrenalectomized) rats decreased by 83% and 58.8%, respectively, on rainy days compared to sunny days. Indomethacin, diclofenac, meloxicam and nimesulide were found to exert anti-inflammatory effects by decreasing adrenaline levels but not affecting corticosterone levels. The anti-inflammatory effects of the tested drugs was eliminated on rainy days due to the low level of corticosterone.

Variance of melatonin and cortisol rhythm in patients with allergic rhinitis

OBJECTIVE Allergic rhinitis is an IgE-mediated inflammatory disease which effects 10%-50% of the normal population. The mechanism of its formation and the circadian rhythm of cortisol and melatonin in allergic rhinitis have not been investigated. STUDY DESIGN Salivary levels of melatonin and cortisol were measured by radioimmunoassay in 35 newly diagnosed allergic rhinitis patients and in 23 control subjects matched for age and gender. RESULTS In the study group; amplitude, baseline and peak levels of salivary melatonin were significantly decreased compared with healty controls (p<0.001). No differences were found in the acrophase and the peak duration of salivary melatonin between the study and control groups (p>0.05). In the study subjects, the circadian rhythm of cortisol was flattened when compared with the control group. The amplitude and the 24h mean levels of salivary cortisol in the study group were significantly lower than in the control group and the acrophase was delayed in patients compared with control subjects (p<0.001). CONCLUSION The circadian rhythms of salivary melatonin and cortisol were found to be disrupted in patients with allergic rhinitis. These results may also be contributive data to explain the pathogenesis of allergic rhinitis and also they can be applicable as adjunctive therapeutic tools in the future and melatonin drugs might be an alternative in the therapy of resistant allergic rhinitis patients or allergic rhinitis patients who cannot use cortisol drugs.

The Effect of Etoricoxib on Hepatic Ischemia-Reperfusion Injury in Rats

Ischemia-reperfusion (I/R) damage is known to be a pathological process which continues with the increase of oxidants and expands with the inflammatory response. There is not any study about protective effect of etoricoxib on the liver I/R damage in literature. Objective. This study investigates the effect of etoricoxib on oxidative stress induced by I/R of the rat liver. Material and Methods. Experimental animals were divided into four groups as liver I/R control (LIRC), 50 mg/kg etoricoxib + liver I/R (ETO-50), 100 mg/kg etoricoxib + liver I/R (ETO-100), and healthy group (HG). ETO-50 and ETO-100 groups were administered etoricoxib, while LIRC and HG groups were orally given distilled water by gavage. Hepatic artery was clamped for one hour to provide ischemia, and then reperfusion was provided for 6 hours. Oxidant, antioxidant, and COX-2 gene expressions were studied in the liver tissues. ALT and AST were measured. Results. Etoricoxib in 50 and 100 mg/kg doses changed the levels of oxidant/antioxidant parameters such as MDA, MPO, tGSH, GSHRd, GST, SOD, NO, and 8-OH/Gua in favour of antioxidants. Furthermore, etoricoxib prevented increase of COX-2 gene expression and ALT and AST levels. This important protective effect of etoricoxib on the rat liver I/R can be tested in the clinical setting.

Serum coenzyme Q10 levels are associated with coronary flow reserve in hemodialysis patients

Accelerated atherosclerosis is the major cause of mortality in patients on chronic hemodialysis (HD). The aim of this study was to evaluate the relation between coenzyme Q10 (CoQ10) levels and coronary flow reserve (CFR) in HD patients as an indicator of atherosclerosis. Seventy‐one chronic HD patients and 65 age‐ and sex‐matched healthy individuals were included in the study. Plasma CoQ10 levels were performed by high‐performance liquid chromatography measurements. CFR was assessed by transthoracic Doppler echocardiography. Serum CoQ10 levels (1.36 ± 0.43 vs. 2.53 ± 0.55, P < 0.001) and CFR values (1.73 ± 0.11 vs. 2.32 ± 0.28, P < 0.001) were significantly lower in HD patients compared with controls. There was a significant positive correlation between CFR and serum levels of CoQ10 (r = 0.669, P < 0.001). A linear regression analysis showed that serum levels of CoQ10 were still significantly and positively correlated with CFR (regression coefficient = 0.235, P < 0.001). Our data have demonstrated that HD patients exhibit decreased plasma CoQ10 levels and CFR values. The study also showed for the first time that serum CoQ10 levels independently predict CFR in HD patients.

Melatonin and cortisol rhythm in patients with extensive nasal polyposis.

PURPOSE Extensive nasal polyposis is an inflammatory disease which effects 1%-4% of normal population. The mechanism of its formation and the circadian rhythm of cortisol and melatonin in ENP have not investigated. MATERIALS AND METHODS Salivary levels of melatonin and cortisol were measured by radioimmunoassay in 31 patients with extensive nasal polyposis and in 27 control subjects matched for age and gender. In both groups none of the subjects did not have obstructive sleep apnea. RESULTS The baseline and the peak levels of salivary melatonin in the extensive nasal polyposis group were significantly lower than in the control group (p<0.001). However, no differences were found in the acrophase and the peak duration of salivary melatonin between the study and control groups (p>0.05). The highest values of melatonin were recorded at 04:00 h in both the study and control groups. The amplitude and the 24 h mean levels of salivary cortisol in the extensive nasal polyposis group were significantly lower than in the control group (p<0.001). The acrophase was delayed by about 8 h in extensive nasal polyposis patients (p<0.001). CONCLUSION The circadian rhythms of salivary melatonin and cortisol were found to be disrupted in patients with extensive nasal polyposis. These results may be applicable as therapeutic tools in the future and melatonin drugs might be useful in the therapy of nasal polyposis like cortisol drugs.