Elevated plasma asymmetric dimethylarginine (ADMA) levels have been implicated in many cardiovascular and metabolic disorders. In the current work, we investigated the hypothesis that peripheral ADMA is an important contributor to opioid tolerance and dependence, by determining plasma ADMA levels during the development of tolerance and dependence to morphine in mice. Tolerance to and dependence on morphine were induced by repeated injections of morphine (10 mg/kg, s.c.) twice daily to male mice, divided into groups of 3-, 6-, 9- and 10-day injection duration. The loss of antinociceptive effect of morphine in the tail flick test was used for evaluating the degree of tolerance. Physical dependence was assessed following the administration of a 5 mg/kg dose of naloxone, by counting the occurrence of withdrawal jumps and forepaw tremors for 20 min. At the end of each period, animals were anesthetized and blood samples were collected from carotid artery. The plasma levels of ADMA, symmetric dimethylarginine (SDMA), l-homoarginine and l-arginine in morphine-tolerant and -dependent mice were not different from duration-matched control mice. Similarly, no difference was observed in plasma ADMA and the other molecules concentrations between groups of mice with different stages of development of tolerance and dependence. Our results suggest that endogenous plasma ADMA, SDMA, l-homoarginine and l-arginine levels remain unchanged during the development of morphine tolerance and dependence, and are not associated with these phenomena.

Aging is an important determinant of vascular disease. Endothelial dysfunction accompanying vascular disease may be related to cardiovascular risk factors such as aging, hypertension, and atherosclerosis. Experimental models suggest that endothelium-derived nitric oxide is reduced with aging, and this reduction is implicated in atherogenesis. The aim of this study was to determine whether increased age resulted in altered serum nitrite and nitrate levels, end-products of nitric oxide, in healthy subjects. Sixty-nine healthy individuals were divided into five different age groups: group I (6–15 years), group II (16–30 years), group III (31–45 years), group IV (46–60 years), and group V (>61 years). In these subjects, serum nitrite was measured by the Griess reaction and nitrate by the nitrate reductase method. Statistical analysis showed that serum nitrite levels were not significantly different in any of the groups, while serum nitrate concentrations exhibited significant differences (P<0.001). These findings suggest that nitric oxide synthesis and/or secretion is reduced with age and consequently endothelium-dependent vasodilation is impaired.

Purpose The prognosis of acute pancreatitis (AP) depends upon the degree of pancreatic necrosis and the intensity of multisystem organ failure. The liver contributes to the systemic manifestations of AP by releasing some cytokines. This study was undertaken to examine comparative effects of melatonin, antioxidant mixture containing L(+)-ascorbic acid and N-acetyl cysteine, pentoxifylline and l-arginine on hepatic damage induced by caerulein-pancreatitis. Results The liver specimens of all groups showed histopathological alterations such as hepatocyte necrosis, intracellular vacuolization, vascular congestion, sinusoidal dilatation and inflammatory infiltration. TEM studies revealed vacuole formation, mitochondrial degeneration, lysosome accumulation and necrosis. The mean histopathological score of the caerulein group was significantly different from that of each treatment group. Conclusionl-Arginine and antioxidant administration be important for reducing hepatic damage induced by AP. Improvement of hepatic damage, in turn, might be beneficial for the prognosis of AP.

Obstructive sleep apnea–hypopnea syndrome (OSAHS) with episodic hypoxia–reoxygenation is associated with increased cardiovascular morbidity and mortality. Therefore, increased homocysteine, asymmetric dimethylarginine (ADMA), oxidative status, and decreased nitric oxide levels have been implicated as possible mechanisms for development of cardiovascular diseases. We aimed to investigate changes in the levels of these substances in patients with OSAHS in comparison with nonapneic controls. Thirty-four OSAHS patients and 15 healthy controls were included in this study. In the blood samples, oxidative status and nitric oxide levels were measured with spectrophotometric methods. Plasma ADMA and homocysteine levels were determined by using high-performance liquid chromatography with fluorescence detection. Nitric oxide levels were significantly low in OSAHS patients (p < 0.05) and correlated with mean SaO₂ (r = 0.513, p < 0.002) and lowest SaO₂ (r = 0.363, p < 0.03). Oxidative status, ADMA, and homocysteine levels were higher in OSAHS patients, but difference did not reach statistical significance. After dividing patients into moderate (AHI = 5–29) and severe (AHI ≥ 30) OSAHS groups, significantly increased homocysteine levels were observed in the severe OSAHS group (p < 0.05). Nitric oxide levels negatively correlated with oxidative status in total OSAHS patients (r = −0.415, p < 0.02) and also in severe OSAHS group (r = −0.641, p < 0.007). Hyperhomocysteinemia and diminished NO production may be causal factors in endothelial dysfunction seen in OSAHS and may explain the association between OSAHS and cardiovascular diseases. These modifiable factors should be monitored in patients suspected of having OSAHS.

Purpose

Epidermal growth factor (EGF) has been used as a vulnerary agent. Epidermal growth factor accelerates wound healing. Nitric oxide (NO) is considered to be an important factor which is involved in wound healing. The objective of this study was to examine the effects of interactions between exogenous EGF and NOx which may have either similar or quite opposed properties in the process of oral wound repair on different days. In addition, lipid peroxidation was found to be an indicator of free radical damage.

Methods

Five-month-old New Zealand albino male rabbits were used for this study. A surgical incision was made in the right mandibula diestema region of the rabbits, which were then divided into controls and EGF implanted groups. All parameters were analyzed by spectrophotometry.

Results

In the EGF-implanted groups, both the NOx and lipid peroxidation indicator levels significantly decreased in comparison to those of the control groups on the first day after wounding. However, on the 3rd and 5th days after wounding, the NOx levels of the tissue strips also decreased in both modalities, but there was no significant alteration between the 3rd and 5th day after wounding.

Conclusion

It was concluded that EGF affects oral wound healing by downregulating both the lipid peroxidation and NOx levels, and it may thus be considered to be an oxygen radical scavenger.

Introduction

We investigated the effect of ginkgo biloba on testicular ischemia-reperfusion (IR) injury.

Materials and methods

Thirty-two Wistar Albino rats were randomly assigned into four groups. Torsion/detorsion (T/D) performed to the rats in group 1, group 2 received ginkgo biloba (50 mg/day) for a month before T/D, group 3 received only gingko biloba (50 mg/day) for a month and group 4 was defined as sham group. After 1 month the testes were removed.

Results

Mean testicular malondialdehyde, nitrate and nitrite levels were significantly increased in group 1 compared to groups 2, 3 and 4 (P < 0.05). The rats in group 3 provided basal histological appearance. In group 1, edema, congestion and hemorrhage between seminiferous tubules were predominant. In group 2, histopathologic features were markedly less than group 1.

Conclusions

Malondialdehyde, nitrate and nitrite levels were increased after unilateral testicular torsion. EGb 761 has a protective effect on testicular injury induced by IR.

We measured the circulatory levels of nitric oxide and estradiol in men over 50 years with esrogenisation findings. We investigated relation between nitric oxide, which is the principal signal for relaxation of vascular smoth muscle cells, and estradiol levels in serum in men over 50 years with estrogenisation. This study included 14 men with (group 1) and 20 without estrogenisation findings (group 2). Mean nitric oxide and estradiol levels were found to be significantly lower in group 2 than group 1. Group 2 had lower levels sex-hormone binding globin and higher both systolic and diastolic blood pressure values than group 1. There was a significant correlation between nitric oxide and estradiol in esrogenisation group.

Background: One of the major adverse effects of long term cyclosporine A (CyA) administration is chronic nephrotoxicity. Several studies have suggested that alterations of the L-arginine (L-Arg) nitric oxide (NO) pathway may be involved in the pathogenesis of CyA-induced kidney damage. Aim: We postulated that in vivo activation of L-Arg-NO pathway might have a beneficial effect on CyA-induced renal damage. Conditions of chronic NO enhancement was established with L-Arg supplementation and chronic NO blockade with N-nitro-L-Arg methyl ester (L-NAME). We tested the hypothesis that, if CyA administration alters intrarenal NO synthesis, then exogenous L-Arg supplementation could limit renal injury, on the contrary, L-NAME, a potent competitive inhibitor of NO synthesis, could enhance CyA nephrotoxicity. Harmful effect of NO blockade indirectly supports the beneficial effect of NO in a model of CyA nephrotoxicity. Methods: Rats were administered vehicle (VH), CyA (7.5 mg/kg/day), CyA + L-Arg (2g/kg/day), CyA + L-NAME (5 mg/100 ml/day), CyA + L-Arg + L-NAME, VH + L-Arg, VH + L-NAME and were sacrificed at the end of the experiment. Body weight, serum creatinine, blood urea nitrogen (BUN) and NO levels were determined. Tubular injury and interstitial fibrosis were evaluated semiquantitatively using scoring systems on paraffin sections stained with hematoxylin/eosin (H/E), Masson’s trichromic and periodic acid-Schiff (PAS). Results: The CyA group developed marked renal injury, characterized by a significant increase in serum creatinine and BUN, and histopathological alterations including tubular dilatation, vacuolization, necrosis, interstitial cell infiltration and tubulointerstitial fibrosis. CyA reduced serum NO level. L-Arg treatment significantly enhanced NO biosynthesis and protected animals from CyA-induced kidney damage. In contrast L-NAME strikingly reduced serum NO level, and worsened biochemical and histopathological alterations. Conclusion: Chronic CyA nephrotoxicity can be aggravated by NO blockade and ameliorated by NO enhancement suggesting that L-Arg supplementation may be protective in CyA nephrotoxicity.

An experimental study was conducted to investigate the effects of allopurinol, which inhibits the enzyme xanthine oxidase, on oxidative stress and on the prevention of stricture development after esophageal caustic injuries in rat. A randomized controlled study was conducted and 60 Wistar albino rats were divided into 6 equal groups, three groups for the acute phase and 3 groups for the chronic phase. Caustic esophageal burn was created by application of 37.5% NaOH to the distal esophagus. Allopurinol was administered at 40 mg/kg daily. Efficacy of the treatment for the acute phase was assessed by measuring tissue malondialdehyde (MDA), nitric oxide (NO) and glutathione (GSH) at the 3rd day; and for the chronic phase by determining tissue hydroxyproline content and histopathologic damage score at the 28th day. We found an increase in XO, MDA and GSH levels and a decrease in NO levels in the acute phase. Allopurinol reinstated the increase in XO significantly, while MDA, GSH and NO levels were reinstated insignificantly. There was no significant difference in means of tissue hydroxyproline content. Histopathologic damage scores were significantly lower in the allopurinol treated group. This study, which is to our knowledge, the first in the literature investigating the influence of allopurinol on caustic esophageal burn, reveals that allopurinol effects MDA, GSH and NO levels insignificantly in the acute phase of caustic esophageal burn and decreases fibrosis significantly in the chronic phase.

We proposed to assess antioxidant status and nitric oxide in fibromyalgia (FM) patients in comparison to healthy controls. Additionally, the association between the serum antioxidant levels and clinical findings in FM patients was also investigated. Thirty-seven FM patients and 37 healthy controls were enrolled in this study. Severity of fatigue and pain were determined by Visual Analogue Scale. Functional capacity in daily living activities was evaluated by fibromyalgia impact questionnaire. Serum NO, catalase and glutathione were measured. Serum glutathione and catalase levels were significantly lower in FM patients than controls. However, no significant difference was seen in serum NO levels between the two groups. A significant correlation was evident between serum NO level and pain. Additionally, the correlation between glutathione level and morning stiffness was found to be significant. These findings support other studies, we assume that these two antioxidants might have impact on the pathogenesis of FM disease.