Anti-inflammatory effects of nesfatin-1 on acetic acid-induced gastric ulcer in rats: involvement of cyclo-oxygenase pathway.

In order to elucidate the contribution of cycloxygenase (COX) enzymes in the anti-oxidant and anti-inflammatory mechanisms of nesfatin-1, which improves the healing process of chronic gastric ulcers, either acetic acid (80%; ulcer groups; n = 40) or saline (control groups; n = 40) was applied to the serosal surface of male Sprague Dawley rats' stomachs for 1 min. Both the control and ulcer groups were treated daily with either i.p. saline or nesfatin-1 (0.3 µg/kg; for 3 days). Nesfatin-1-treatment was preceded with i.p. saline, COX-2 inhibitor NS-398 (2 mg/kg), COX-1 inhibitor ketorolac (3 mg/kg) or non-selective COX inhibitor indomethacin (5 mg/kg) for 3 days. The rats were decapitated at the end of the third day, and their trunk blood was collected for the measurements of tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß) and IL-10 using ELISA. The induction of ulcers resulted in increased macroscopic scores, along with elevated gastric malondialdehyde, luminol- and lucigenin-enhanced chemiluminescence levels and myeloperoxidase activity. On the other hand, nesfatin-1 treatment abolished these elevations. Depleted glutathione, superoxide dismutase and catalase activity levels in the saline-treated ulcer group were preserved in the nesfatin-1-treated ulcer group. Increased levels of serum TNF-α, IL-1ß, IL-10 in the saline-treated ulcer group, as compared to control group, were significantly decreased in the nesfatin-1-treated ulcer group. The inhibition of COX-1, and/or COX-2 reversed most of the alterations induced with nesfatin-1, but COX-2-blockade was consistently more effective to abolish all nesfatin-1-induced changes. Our results suggest that nesfatin-1 ameliorates ulcer-induced inflammatory response through the modulation of oxidant-antioxidant balance. As selective pharmacological inhibition of COX-1 or COX-2 suppresses the antioxidant/anti-inflammatory effects of nesfatin-1, it appears that nesfatin-1 decreases inflammatory mediators and neutrophil migration by a COX-dependent mechanism, especially by a COX-2- dependent mechanism, during the ulcer healing stage.

The effect of estrogen receptor agonists on pancreaticobiliary duct ligation induced experimental acute pancreatitis.

The 17ß-estradiol plays a role in physiology of pancreas and may protect it from inflammation. To examine the possible anti-inflammatory effects of 17ß-estadiol in pancreaticobiliary duct ligated (PBDL) acute pancreatitis (AP) model, and the underlying mechanism that 17ß-estradiol acts on, via evaluating the direct and the receptor related effects by using 17ß-estradiol, ER-α and -ß agonists. In the study both sexes of rats (n = 88) were used. Animals were divided into two groups as PBDL and PBDL + ovariectomized. ER-α agonist propyl-pyrazole-triol (PPT; 1 mg/kg/day), ER-ß agonist diarylpropionitrile (DPN; 1 mg/kg/day) and 17ß-estradiol (10 mg/kg/day) were administered to the groups for 3 days following AP induction. On the 3rd day, lung and pancreas tissues and serum samples were taken for malondialdehyde (MDA), glutathione (GSH), myeloperoxidase (MPO), superoxide dismutase (SOD) and interleukin (IL) assays, and histological analyses. In both tissues of male and female AP groups MPO, MDA, SOD levels were increased (P < 0.05 - 0.01) and GSH levels were decreased (P < 0.05). Pancreas and lung MDA and SOD levels were improved with all treatments in female, except lung MDA levels of PPT-treated ones, while lung MDA and SOD levels were improved by PPT and 17ß-estradiol in females and via PPT in males (P < 0.05 - 0.001). The increased MPO levels were inhibited with PPT in male pancreas and female lung and with 17ß-estradiol in female pancreas (P < 0.05). The increased pro-inflammatory ILs were declined by treatments (P < 0.05 - 0.001). 17ß-estradiol and ER-α and -ß agonists reduced oxidative pancreatic and pulmonary damage. Estrogen and agonists might have protective role in AP.

L-Carnitine ameliorates methotrexate-induced oxidative organ injury and inhibits leukocyte death.

Methotrexate (MTX), a folic acid antagonist widely used for the treatment of a variety of tumors and inflammatory diseases, affects normal tissues that have a high rate of proliferation, including the hematopoietic cells of the bone marrow and the gastrointestinal mucosal cells. To elucidate the role of free radicals and leukocytes in MTX-induced oxidative organ damage and the putative protective effect of L-carnitine (L-Car), Wistar albino rats were administered a single dose of MTX (20 mg/kg) followed by either saline or L-Car (500 mg/kg) for 5 days. After decapitation of the rats, trunk blood was obtained, and the ileum, liver, and kidney were removed for histological examination and for the measurement of malondialdehyde (MDA) and glutathione (GSH) levels, myeloperoxidase (MPO) activity, and collagen content. Our results showed that MTX administration increased the MDA and MPO activities and collagen content and decreased GSH levels in all tissues, while these alterations were reversed in L-Car-treated group. The elevated serum TNF-alpha level observed following MTX treatment was depressed with L-Car. The oxidative burst of neutrophils stimulated by Annexin V was reduced in the saline-treated MTX group, while L-Car abolished this inhibition. Similarly, flow cytometric measurements revealed that leukocyte apoptosis was increased in MTX-treated animals, while L-Car reversed these effects. Severe degeneration of the intestinal mucosa, liver parenchyma, and glomerular and tubular epithelium observed in the saline-treated MTX group was improved by L-Car treatment. These results suggest that L-Car, possibly via its free radical scavenging and antioxidant properties, ameliorates MTX-induced oxidative organ injury and inhibits leukocyte apoptosis. Thus, supplementation with L-Carnitine as an adjuvant therapy may be promising in alleviating the systemic side-effects of chemotherapeutics.

Early pulmonary involvement in Niemann-Pick type B disease: lung lavage is not useful.

Niemann-Pick disease (NPD) is a rare, autosomal-recessively inherited lipid storage disease which is characterized by intracellular deposition of sphingomyelin in various body tissues. The disease is heterogeneous and classified into six groups. Pulmonary parenchymal involvement may be a feature of several subtypes of NPD, including type B. Progressive pulmonary involvement in NPD type B is a major cause of morbidity and mortality. It is usually diagnosed at older ages. Only a few cases with early pulmonary involvement have been reported. In this report, a patient with NPD type B, hospitalized with the diagnosis of pneumonia at age 3 months, is presented. Following treatment for pneumonia, she continued to have persistent respiratory symptoms and became oxygen-dependent. High-resolution computed tomography of the chest revealed diffuse interstitial changes. During follow-up, the patient developed hepatosplenomegaly. Lung, liver, and bone marrow biopsies showed characteristic findings for NPD. Biochemical studies also confirmed the diagnosis, and the sphingomyelinase enzyme level of the patient was low. Unilateral lung lavage was performed in order to decrease lipid storage as a treatment modality. However, there was no clinical or radiological improvement. The patient died at age 15 months due to progressive respiratory failure. Pulmonary involvement is a rare entity in early childhood in patients with NPD type B, but should be considered in the differential diagnosis of persistent interstitial lung disease. It may cause progressive respiratory failure, but the treatment options remain limited.

Effect of aging on the distribution of basic fibroblast growth factor immunoreactive cells in the rat hippocampus.

Hippocampal formation is extremely sensitive to the aging process and appears to be one of the first regions to show structural and physiological changes with advancing age. Basic fibroblast growth factor (bFGF) plays an important role in the stimulation of mitogenesis in glial cells, the support of neuronal survival and the promotion of neurite outgrowth in vitro. In the present study, the effect of aging on the distribution of bFGF immunoreactive (bFGF-ir) cells was investigated. The protein product of bFGF was visualized immunohistochemically in the dorsal hippocampus of Wistar albino rats. bFGF-ir astrocytes in different subfields of hippocampus and neurons in CA2 field were quantified to determine whether changes in immunoreactivity were correlated with advancing age. Aging was accompanied by a decrease in bFGF-ir cell density in subfields of hippocampus. We concluded that aging was associated with a reduction in bFGF-ir cell density that may reflect a decreased expression of bFGF in the rat hippocampus.