Regular exercise alleviates renovascular hypertension-induced cardiac/endothelial dysfunction and oxidative injury in rats.

The importance of physical activity in the management of renovascular diseases is well-known, but lacks evidence of underlying mechanisms. The purpose of the study was to elucidate the protective/therapeutic effects of regular exercise on experimental renovascular hypertension (RVH)-induced oxidative stress and cardiac dysfunction. Wistar albino rats underwent a RVH surgery (2K1C, Goldblatt). Three weeks later half of the rats started swimming exercise for 9 weeks (n = 15), while the sedentary RVH group (n = 15) had no exercise during that period. Sham-operated control rats (n = 10), had the similar surgical procedures but the left renal artery was left unclipped. Body weights were monitored, and blood pressures were measured weekly using tail-cuff. Echocardiographic evaluation was performed on the 3(rd) week and on the 12(th) week of the experiment before the rats were decapitated. Heart and thoracic aorta were removed and serum was collected, while aortic samples were put in a 10% formaldehyde solution for immunochemistry. Cardiac tissue samples obtained from each animal were used for the determination of tissue myeloperoxidase (MPO) and catalase (CAT) activities, malondialdehyde (MDA), and glutathione (GSH) levels. In the sedentary RVH group, aortic contractile response (contraction/relaxation in isolated organ bath), left ventricular diastolic and systolic dimensions, and immunohistochemical staining of aortic inducible nitric oxide synthase (iNOS) were increased, while ejection fraction and aortic endothelial nitric oxide synthase (eNOS) staining were decreased. RVH in the sedentary rats resulted in increased pro-inflammatory cytokines (TNF-α, IL-2, IL-6), lipid peroxidation (malondialdehyde) and neutrophil infiltration (myeloperoxidase activity) along with reductions in antioxidant glutathione and catalase levels in the cardiac tissue. Exercise after RVH increased the immunohistochemical staining of aortic eNOS, decreased iNOS staining and reversed the alterations in echocardiographic and oxidative parameters. Regular exercise commenced after RVH surgery alleviated renovascular hypertension-induced oxidative injury, by modulating oxidant-antioxidant balance via the involvement of the endothelial NO system.

The effects of alpha-lipoic acid on nitric oxide synthetase dispersion in penile function in streptozotocin-induced diabetic rats.

Diabetes-induced erectile dysfunction is one of the most prevalent complications of diabetes in males. alpha-Lipoic acid (ALA) and its reduced form, dihydrolipoic acid, are powerful antioxidants. Data strongly suggest that, because of its antioxidant properties, ALA is particularly suited to the prevention and/or treatment of diabetic complications that arise from overproduction of reactive oxygen and nitrogen. The aim of this study was to investigate the localization of nitric oxide synthetase (NOS) in normal and diabetic rat cavernous smooth muscles and to examine the effects of ALA on them. Rats were divided into four groups: control, diabetic, diabetic plus ALA, and ALA only. Penile tissues were taken 15 days after drug application and examined histochemically and immunohistochemically. Comparison of the control and diabetic groups revealed that the axons of nerve cells were not identified with Masson trichrome in the diabetic group, whereas in the control group NOS localization and immunostaining (endothelial NOS [eNOS]) were normal. Diabetic rats administered ALA showed improvement in Masson trichrome, nicotinamide adenine dinucleotide phosphate diaphorase (NADPH-d) and eNOS localization compared with untreated diabetic rats. Although there was no difference between the control group and the group administered ALA only, we observed an increase in NADPH-d and eNOS. In erection, eNOS and neuronal NOS (nNOS) may have a significant role. In pathologic conditions, erectile dysfunction may occur as a result of an increase in inducible macrophage-type NOS (iNOS). ALA plays an important role in treatment of erectile dysfunction by decreasing iNOS and increasing other isoforms of NOS.

Early histological changes of ileal mucosa after augmentation cystoplasty.

Segments of bowel are used routinely for transplantation in various pathological conditions such as contracted bladders or poorly compliant neuropathic bladders. However, little is known how these intestinal segments adopt to a toxic environment caused by urine. Therefore, the present study was performed to determine early histological changes of ileal mucosa after augmentation cystoplasty. Seven patients with augmentation cystoplasty underwent random cold-cup biopsies of ileal segments after a mean period of 14.4 months after cystoplasty and morphological changes were evaluated using light microscopy and transmission and scanning electron microscopy. Most pronounced features were varying degrees of villous atrophy, increased numbers of Paneth and goblet cells. Severity of atrophic villous changes were not related to the length of the interval between surgery and endoscopic biopsy. These findings may be explained as adaptations of bowel tissue to counteract noxious effects of urine and to maintain its epithelial function in the bladder.

Protective effect of famotidine, omeprazole, and melatonin against acetylsalicylic acid-induced gastric damage in rats.

It has been reported that both omeprazole and famotidine have a protective effect against gastric mucosal damage induced by acetylsalicylic acid (ASA) and other nonsteroidal anti-inflammatory drugs. Since active oxygen species and lipid peroxidation were reported to play a role in the pathogenesis induced by ASA, we aimed to study if omeprazole and famotidine have any antioxidant effect by comparing their protective effect with that of melatonin, an effective antioxidant and free radical scavenger. Mucosal damage was evaluated by macroscopic examination, histological analysis and by measurement of lipid peroxidation (LPO), glutathione (GSH), and myeloperoxidase (MPO) activity. Omeprazole (20 micromol/kg per os), famotidine (3 mg/kg per os), and melatonin (10 mg/kg intraperitoneally) significantly prevented gastric ulcerogenesis induced by ASA (200 mg/kg per os) and decreased the ulcer index. Gastric LPO and MPO activity that were increased significantly by ASA were decreased after treatment with omeprazole, famotidine, and melatonin. ASA treatment decreased significantly the gastric GSH levels, and pretreatment with omeprazole, famotidine, or melatonin increased it significantly. Famotidine and omeprazole decreased the gastric acidity, which was increased by ASA, whereas melatonin had no effect on this parameter. These findings suggest that active oxygene species and LPO have an important role in the pathogenesis of gastric mucosal damage induced by ASA and that both famotidine and omeprazole may be protective against this damage, although they were not as efficient as melatonin as an antioxidant. On the other hand, the antisecretory effect of omeprazole and famotidine may also be contributing to their antiulcer effect.

Acute lung injury following thermal insult to the skin: a light and transmission electron microscopial study.

Oxygen radicals are involved in the development of burn shock and distant organ injury in animal models of trauma. Neutrophils are likely the source of reactive oxygen metabolites as a result of the systemic inflammatory reaction to a local burn insult. The aim of the present study was to assess the role of neutrophils in the development of lung injury related to second degree skin burn in rats. Rats were decapitated at two hours following burn injury. Lung tissue samples were removed and examined biochemically and histologically. Tissue-associated myeloperoxidase (MPO) activity, which is an index of neutrophil infiltration, was increased considerably in lung tissue at 2 h after burn injury. Disturbance of alveolar structure, intraalveolar hemorrhage and prominent neutrophil infiltration indicated lung parenchymal injury. Ultrastructural examination of the lung revealed that pneumocytes type I, pneumocytes type II and capillary endothelial cells were degenerated. The data presented here suggest that neutrophil accumulation in the lung is involved in pathogenesis of this distant organ after burn injury.

Motor neuron degeneration due to aluminium deposition in the spinal cord: a light microscopical study.

For a long time, aluminium has been considered as an indifferent element from a toxicological point of view. In recent years, it became clear that aluminium is a potential toxic agent in humans and has been implicated in the pathogenesis of several clinical disorders, such as dementia, respiratory tract disorders and allergic reactions. Chronic exposure to aluminium fumes, inhalation of aluminium and aluminium-oxide powder increase the risk to develop serious central nervous system pathology, in particular Alzheimer's disease and amyotrophic lateral sclerosis (ALS). In the present study, 3 experimental and 1 control group of rats were used to study the effects of aluminium on the central nervous system. Aluminium was injected intracisternally as a single dose (50 micrograms for group I, 100 micrograms for group II and 300 micrograms for group III) to the experimental groups (n = 5 in each group). The same dose was given at 3 months after the first injection to all groups. The control group (n = 5) was intracisternally given a physiological salt solution. Electromyography (EMG) was applied to the rats of the experimental groups. Rats were decapitated at 3 months after the second injections. Spinal cord samples from lumbar and cervical regions were removed and histological examination was performed. Light microscopical investigations revealed severe degeneration in motor neurons of the rats treated with 300 micrograms. Neurofibrillary tangle formation, chromatolysis and abnormal localization of the nuclei were found in swollen perikarya. Extreme loss of motor neurons with "ghost cell" appearance was found in that group. Sections of spinal cords of rats treated with lower doses of aluminium showed a moderate degree of motor neuron damage. EMGs of rats treated with the high dose of aluminium revealed severe acute denervation whereas treatment with lower doses resulted in moderate denervation. We conclude that aluminium may cause severe motor neuron damage in rat spinal cord resembling ALS.