Dynamic Thiol/Disulphide Homeostasis in Acute Urticaria.

BACKGROUND: Urticaria is an unknown, sudden, and itchy skin disease that is recognized with redness, swelling, and is sometimes seen with angioedema. It is classified as acute or chronic, depending on the duration of symptoms. Thiols in plasma are powerful antioxidants that physiologically eliminate free radicals. The mostly and rapidly affected proteins are thiols that contain the sulfhydryl group. In the present study, the thiol/disulfide homeostasis was investigated as a brand new indicator of oxidative stress in patients who had acute urticaria and presented to the emergency department. OBJECTIVE: In the present study, the thiol/disulfide homeostasis, ischemia-modified albumin (IMA), and and neutrophil lymphocyte ratio (N/L ratio) were investigated in the etiopathogenesis of acute urticaria. MATERIAL AND METHOD: A total of 37 patients and 40 healthy volunteers were included in the study. Thiol/disulfide homeostasis (TDH) [total thiol-native thiol/disulfide changes] was measured in both groups (patient group and control group) using a brand novel method developed by Erel and Neselioglu. Half of the difference between total thiol and native thiol concentrations gives the amount of disulfide bond. RESULTS: Total thiol and native thiol levels in blood were found to be low. The levels of total thiol (P = 0.218) and native thiol (P = 0,001) were significantly lower in patients with acute urticaria than in the control group. At the same time, the level of disulfide was significantly higher in the patient group than in the control group (P = <0.001). The level of IMA was higher in the patient group than in the control group (P < 0.001). CONCLUSION: While total thiol and native thiol are low in acute urticaria, the levels of disulfide and IMA are high.

Accelerated forgetting and verbal memory consolidation process in idiopathic nondement Parkinson's disease.

OBJECTIVE: Episodic memory impairment and underlying pathophysiology in Parkinson's Disease (PD) is poorly investigated. Formerly, it was thought to be a secondary effect of impairment in fronto-striatal circuit. However, recent studies hypothesized that there is a dual progression of PD and memory loss is possibly related to posterior cortex rather than frontal. To understand the impairment, underlying mechanisms should be investigated. Although consolidation is one of these mechanisms consolidation phase of episodic memory in PD was not investigated yet. Recently accelerated long term forgetting (ALF) phenomenon is emphasized in consolidation researches. METHOD: Here it is evaluated the presence of accelerated long-term forgetting in nondemented PD as a consequence of a deficit in consolidation process. 32 patients and 33 controls participated in the study. Turkish Verbal Memory Process Test (VMPT) was applied to both groups. Delayed recall (DR) scores collected after 30 min, one week and six weeks. Forgetting rates were calculated based on these scores. RESULTS: There was significant difference in DR scores of patients compared to controls in the 30th minute and sixth week. Forgetting rate between 30th minute-1st week did not differ but 1st-6th week was found statistically significant across groups. CONCLUSIONS: To the best of our knowledge, this is the first study investigating verbal memory consolidation in PD. Results suggested that impairment is possibly related to the late phase of consolidation of verbal memory in neocortex.

Changes in kidney tissue and effects of erythropoietin after acute heart failure.

Impairment of cardiac function causes renal damage. Renal failure after heart failure is attributed to hemodynamic derangement including reduced renal perfusion and increased venous pressure. One mechanism involves apoptosis and is defined as cardiorenal syndrome type 1. Erythropoietin (EPO) is a cytokine that induces erythropoiesis under hypoxic conditions. Hypoxia inducible factor 1 alpha (HIF-1α) plays a regulatory role in cellular response to hypoxia. Protective effects of EPO on heart, kidney and nervous system are unrelated to red blood cell production. We investigated early changes in and effects of EPO on renal tissues of rats with myocardial infarction by morphology and immunohistochemistry. Coronary artery ligation was used to induce myocardial infarction in Wistar rats. Group 1 comprised sham operated rats; groups 2, 3 and 4 included rats after coronary artery ligation that were sacrificed 6 h after ligation and that were treated with saline, 5,000 U/kg EPO or 10,000 U/kg EPO, respectively; group 5 included rats sacrificed 1 h after ligation. Group 2 showed increased renal tubule damage. Significantly less tubule damage was observed in EPO treated groups. EPO and EPO receptor (EPO-R) immunostaining intensities increased slightly for group 5 and became more intense for group 2. EPO and EPO-R immunostaining was observed in the interstitial area, glomerular cells and tubule epithelial cells of EPO treated groups. HIF-1α immunostaining was observed in collecting tubules in the medulla only in group 2. Caspase-3 immunostaining is an indicator of apoptosis. Caspase-3 staining intensity decreased in renal medulla of EPO treated groups. EPO treatment may exert a protective effect on the renal tissues of patients with cardiorenal syndrome.

Risk for malignant and borderline ovarian neoplasms following basic preoperative evaluation by ultrasonography, ca125 level and age.

OBJECTIVE: To verify the basic preoperative evaluation in the discrimination between benign and malignant adnexal masses in our clinical practice. MATERIALS AND METHODS: Data were collected on the records of 636 women with adnexal masses who had undergone surgery either by open or endoscopic approaches. Those with obvious signs of malignancy, any history of cancer, emergency surgeries without basic evaluation were excluded. The preoperative features by age, ultrasound and serum Ca125 level were compared with final histopathological diagnosis at the four departments of the institution. These are the general gynecology (Group 1: exploratory laparotomy), the gynecologic endoscopy (Group 2: laparoscopy and adnexectomy), the gynecological oncology (Group 3: staging laparotomy) and the gynecologic endocrinology and infertility (Group 4: laparoscopy and cystectomy). RESULTS: There were simple and complex cyst rates of 22.3% and 77.2%, respectively. There were 86.3% benign, 4.1% (n:20) borderline ovarian tumor (BOT) and 6.4% (n:48) malignant lesions. There were 3 BOT and 9 ovarian cancers in Group 1 and one BOT and two ovarian cancer in the Group 2. During the surgery, 15 BOT (75%) and 37 ovarian cancer (77%) were detected in the Group 3, only one BOT was encountered in the Group 4. The risk of rate of unsuspected borderline or focally invasive ovarian cancer significantly increased by age, size, complex morphology and Ca125 (95% CI, OR=2.72, OR=6.60, OR=6.66 and OR=4.69, respectively). CONCLUSIONS: Basic preoperative evaluation by comprehensive ultrasound imaging combined with age and Ca125 level has proved highly accurate for prediction of unexpected malignancies. Neither novel markers nor new imaging techniques provide better information that allow clinicians to assess the feasibility of the planned surgery; consequently, the risk of inadvertent cyst rupture during laparoscopy may be significantly decreased in selected cases.

Quercetin protects radiation-induced DNA damage and apoptosis in kidney and bladder tissues of rats.

Ionizing radiation (IR) can induce cell damage and cell death through the reactive oxygen species generated by radiolytic hydrolysis. The present study was aimed to determine the possible protective effects of quercetin, a well-known antioxidant agent, against IR-induced bladder and kidney damage in rats. Sprague-Dawley rats were exposed to 8-Gy whole-abdominal IR and given either vehicle or quercetin (20 mg/kg, ip). Rats were decapitated at either 36 h or 10 days following IR, where quercetin or vehicle injections were repeated once daily, and kidney and bladder samples were obtained for the determination of myeloperoxidase and caspase-3 activities, an index of tissue neutrophil infiltration and apoptosis, respectively. Radiation-induced inflammation was evaluated through tissue cytokine, TNF-α levels. In order to examine oxidative DNA damage, tissue 8-hydroxydeoxyguanosine (8-OHdG) levels were measured. All tissues were also examined microscopically. In the saline-treated irradiation groups, myeloperoxidase and caspase-3 activities, 8-OHdG and TNF-α levels were found to be increased in both tissues (p < 0.05). In the quercetin-treated-IR groups, all these oxidant responses were prevented significantly (p < 0.05). The present data demonstrate that quercetin, through its free radical scavenging and antioxidant properties, attenuates irradiation-induced oxidative organ injury, suggesting that quercetin may have a potential benefit in radiotherapy by minimizing the adverse effects and will improve patient care.

The protective effect of oxytocin on ischemia/reperfusion injury in rat urinary bladder.

Oxytocin (OXY), a well-known nonapeptide, plays a crucial role in reproduction, and has effects on modulating the immune and inflammatory processes in living organisms as well. Recently it is also known as an antioxidant in several organs. The present study aims to demonstrate the protective effect of OXY against ischemia/reperfusion (I/R) injury in urinary bladder tissue. Abdominal aorta of rats, were clamped to perform urinary bladder ischemia. OXY (0.5 µg/kg) was injected intraperitoneally before ischemia in I/R+OXY group, whereas the vehicle solution was injected to I/R group. At the end of reperfusion, tissue samples from urinary bladder were processed for histochemical, ultrastructural and biochemical analysis. Tissue sections were stained by toluidine blue for mast cell counting and hematoxylin-eosin for histopathology. In addition, malondialdehyde (MDA) and glutathione (GSH) levels were determined biochemically. The results demonstrated that there was an extreme damage at urothelium, dilatation of intercellular junctions, inflammatory cell infiltration in I/R group. I/R+OXY group demonstrated a reduction in the severity of urinary bladder damage. According to mast cell counting results, both granulated and degranulated mast cells were decreased in I/R+OXY group compared to I/R group. The mean MDA level was higher in I/R group compared to control and lower in I/R+OXY group compared to I/R group. GSH level reduced in I/R group compared to the control and increased in I/R+OXY group compared to I/R group. In conclusion, oxytocin, as confirmed by histological evaluation and biochemical assays has a potential protective effect in the urinary bladder tissue against ischemia/reperfusion injury.

Effect of topical insulin on cutaneous wound healing in rats with or without acute diabetes.

BACKGROUND: Diabetes is a condition known even in its early stages to impair the normal course of wound healing, thus leading to chronic wounds. The role of insulin in the regulation of energy metabolism, protein synthesis, cell differentiation and growth suggests that this hormone could also play an essential role in regulation of wound healing. AIM: To determine the effects of topical insulin administration on wound healing in rats with or without acute diabetes. METHODS: This study was conducted using four groups of male Sprague-Dawley rats: (i) nondiabetic rats receiving topical insulin (n = 7), (ii) nondiabetic rats receiving topical sterile water (n = 7), (iii) diabetic rats receiving topical insulin (n = 7) and (iv) diabetic rats receiving topical sterile water (n = 7). Wound healing was assessed by wound contraction rate, complete epithelialization time and histological results. RESULTS: Topical insulin enhanced wound healing by shortening the time needed for complete epithelialization in both the nondiabetic and acute diabetic groups. The histological observations supported the planimetric results in both groups. CONCLUSIONS: This study revealed that topical insulin application to cutaneous wounds accelerates wound healing in rats with or without acute diabetes.

Determination of malondialdehyde, reduced glutathione levels and APOE4 allele frequency in late-onset Alzheimer's disease in Denizli, Turkey.

OBJECTIVES: The aim of the present study was to determine the Apolipoprotein E (APOE) 4 allele frequency of patients with late-onset Alzheimer's disease (AD) and to determine the effects of oxidant-antioxidant balance on AD. DESIGN AND METHODS: PCR-RFLP was undertaken in 62 cases with AD and 56 aged-matched controls. Activities of reduced glutathione (GSH) and malondialdehyde (MDA) concentration were measured in same groups. RESULTS: Patients with at least one E4 allele genotype were significantly different in patients with AD (21%) than controls (9%) (p=0.01). Serum MDA levels were significantly different between AD patients and Control group (p=0.0001). There was no significant difference in serum GSH levels between AD patients and C groups. CONCLUSION: These results confirmed that the APOE4 allele occurs frequently in late onset AD compared with normal controls. Also elevated MDA levels are likely an essential factor in the pathogenesis and neuronal damage of AD.

A comparative ontogenic study of urinary bladder: impact of the epithelial differentiation in embryonic and newborn rats.

The present study aimed to show the cellular and subcellular distribution of glycogen content during the differentiation of urothelial cells from simple cuboidal to stratified transitional epithelium. Bladder samples were taken from rat embryos on the 15th to 19th days and newborn at 21st day. During the development of the bladder, the formation of fusiform vesicles, asymmetric unit membrane (AUM) and microridges were examined with staining with haematoxylin-eosin and periodic acid Schiff for light microscope and periodic acid-thiocharbohydrazide-silver proteinate for transmission electron microscope. The topographical changes of luminal differentiation were examined with the scanning electron microscope. The urothelium was simple cuboidal from 15th till the 17th days of gestation. Glycogen content was present in the cytoplasm till the 18th day of gestation. At the early stage (16th day) of gestation, the apical surface contains microvilli that points the undifferentiated cells. The density of microvilli decreased and ropy microridges appeared at the 17th day of gestation. The small discoid vesicles lined with AUM developed at the apical cytoplasm of the surface cells at the 17th day of gestation. After this stage, both the density of microridges and large and elongated fusiform vesicles increased. The differentiation of the urothelium begins with the formation of the round and small vesicles, continues with the formation of the AUM and at the final stage there is a decrease in both glycogen content and the appearance of the microridges at the luminal surface of the urothelial cells.

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.

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.

NK-1 antagonist CP99994 inhibits stress-induced mast cell degranulation in rats.

Mast cells are implicated in stress-induced inflammatory skin diseases such as psoriasis. Mechanisms of stress-induced mast cell degranulation however, are not entirely clear. Here we explore the role of activation of a Substance P (SP) receptor (NK-1) on mast cell degranulation upon exposure to stress in rats. A specific nonpeptide NK-1 antagonist, CP99994 was used to treat the rats either peripherally or intracerebroventricularly. Because increased SP activity in the brain may mediate the stress response, we also examined cutaneous mast cell degranulation after central injection of SP. Stress, as well as SP injected centrally, increased mast cell degranulation. Both central and peripheral injection of CP99994 prevented stress-induced mast cell degranulation. Surprisingly, the combination of stress with SP decreased mast cell degranulation, suggesting that high levels of SP may counteract the stress responses. Results in this animal model suggest that NK-1 antagonists may be used therapeutically to treat stress-induced inflammatory skin diseases; however, drug doses should be chosen carefully.

The effects of quantum energy surgical device and of bipolar coagulation: a comparative experimental study.

OBJECTIVE: The quantum energy surgical device (QESD) employs an innovative, "no-touch" thermal coagulation, incision and evaporation technique in which thermal energy is delivered to tissue in the format of high-energy neutral argon gas atoms. The aim of this study is to compare QESD and bipolar coagulation (BC) through assessment of both haemostasis and histological damage to isolated femoral arteries of rats. METHODS: Sixty rats were randomly divided into acute and short-term experimental groups. In the acute group (n=20) histopathological evaluation was performed immediately following coagulation, whereas in the short-term experimental group (n=20) the evaluation was performed 10 days later. Each sham group consisted of ten rats. Viewed under the surgical microscope, only normal-appearing, freshly sectioned, and bleeding femoral arteries were studied. Right femoral arteries subject to QESD coagulation, and left femoral arteries to BC. Haemorrhaging was controlled using the minimal coagulation time necessary to stop it. All vascular layers, including endothelium, internal elastic lamina, media and adventitia were examined histologically and ultrastructurally in a "blind" fashion to critically compare morphological damage due to QESD and BC. RESULTS: Surgical haemostasis induced by QESD was found to be as safe as BC. Light microscopy revealed more marked histopathological changes in the BC than in the QESD group. These involved mainly the endothelial and medial compartments and, at the ultrastructural level, consisted of endothelial degeneration and exfoliation, irregularity of internal elastic lamina, degeneration, and loss of medial smooth muscle. CONCLUSION: The results indicate that QESD coagulation induces significantly less histological damage than does BC. Thus QESD coagulation is a safe, less tissue destructive, and equally effective method of haemostasis.

Morphological examination of the effects of defibrotide on experimentally induced bladder injury and its relation to interstitial cystitis.

This morphological study aims to investigate the effects of defibrotide, a deoxyribonucleic acid derivative drug with cytoprotective, immunosuppressive and vasorelaxant effects, on protamine sulfate induced bladder injury. Wistar albino female rats were catheterized and intravesically infused with phosphate buffered solution (control group) or, either protamine sulfate (bladder injury group) or protamine sulfate+defibrotide (bladder injury+defibrotide group) dissolved in phosphate buffered solution. The morphology of the urinary bladder was investigated using light and electron microscopy. The number of mast cells in the mucosa, mucosal alterations, intercellular junctions, surface topography and the glycosaminoglycan (GAG) layer as well as microvillus formation on the luminal surface were evaluated. In the bladder injury group, ulcerated areas, irregularity of the GAG layer, increased number of mast cells, vacuole formation, dilated perinuclear cistern, formation of pleomorphic and uniform microvilli and dilatations in the intercellular spaces in the urothelium were observed. In the bladder injury+defibrotide group a relatively normal urothelial topography, GAG layer and a few mast cells in the mucosa, some dilatations between the intercellular areas, less uniform microvilli, regular perinuclear cistern and tight junctions were observed. These results show that defibrotide can inhibit PS induced bladder damage.

[N,N'-bis(salicylidene)-2,2-dimethyl-1,3-propanediaminate]nickel(II) and [N,N'-bis(salicylidene)-2,2-dimethyl-1,3-propanediaminate]copper(II).

In the title compounds, [2,2'-[2,2-dimethyl-1,3-propanediylbis(nitrilomethylidyne)]diphenolato-kappa4N,N',O,O']nickel(II), [Ni(C19H20N2O2)], and [2,2'-[2,2-dimethyl-1,3-propanediylbis(nitrilomethylidyne)]diphenolato-kappa4N,N',O,O']copper(II), [Cu(C19H20N2O2)], the Ni(II) and Cu(II) atoms are coordinated by two iminic N and two phenolic O atoms of the N,N'-bis(salicylidene)-2,2-dimethyl-1,3-propanediaminate (SALPD2-, C17H16N2O2(2-)) ligand. The geometry of the coordination sphere is planar in the case of the Ni(II) complex and distorted towards tetrahedral for the Cu(II) complex. Both complexes have a cis configuration imposed by the chelate ligand. The dihedral angles between the N/Ni/O and N/Cu/O coordination planes are 17.20 (6) and 35.13 (7) degrees, respectively.

Role of afferent neurons in stress induced degenerative changes of the bladder.

PURPOSE: We investigated the role of afferent C fibers in morphological changes of the rat bladder during stress. MATERIALS AND METHODS: Wistar albino rats were exposed to cold immobilization stress. Different routes of capsaicin administration before cold immobilization stress were studied. Capsaicin was given to neonates, around the vagus (perivagal) or celiac (periceliac), or perivagal plus periceliac. From each group samples of bladder were randomly chosen for morphological evaluation using electron microscopy. RESULTS: Stress exposure led to pathological changes, including an increased number of mast cells, degenerated urothelium and dilated tight junctions, in the bladder. Capsaicin given neonatally and around the vagal and celiac ganglia prevented these stress induced degenerative bladder changes. CONCLUSIONS: Activation of capsaicin sensitive afferent neurons locally and centrally may be involved in stress related pathological changes in the rat bladder.

Beneficial effects of glycocholic acid (GCA) on gut mucosal damage in bile duct ligated rats.

In order to investigate the effect of bile acids on gastrointestinal inflammations, bile duct ligated rats (BDL) were treated with GCA (25 mM/ml, oral or colonic) or saline I h before ethanol challenge and twice daily for 3 days in the ileitis group, while GCA was given twice daily for 3 days in the colitis group. BDL reduced the macroscopic and microscopic damage scores in the ileitis group compared to sham operated group, while it had no significant effect on ulcer or colitis groups. However, GCA given in BDL group reduced the ulcer index and microscopic damage in colitis group compared to saline-treated groups, but had no effect in ileitis group. Both BDL and GCA administration in BDL group reduced ileitis- or colitis-induced elevations in MPO levels. GCA administration in BDL group inhibited gastric acid output and volume. Our results suggest that oral or colonic administration of primary bile acids may be useful for the treatment of gastrointestinal inflammations.

The effect of alpha-melanocyte stimulating hormone on endotoxin-induced intestinal injury.

We investigated the effect of alpha-melanocyte stimulating hormone (alpha-MSH) on endotoxin-induced intestinal inflammation and the role of nitric oxide and prostaglandins in this response. alpha-MSH treatment (25 microg/rat, intraperitoneally (i.p.); twice daily) reduced the severity of the lesions macroscopically and microscopically. This protective effect was found to be confined mainly to the distal ileum. These lesions were reversed by pretreatment with the non-selective COX inhibitor indomethacin (10 mg/kg, subcutaneously (s.c.)) but not by the selective COX-2 inhibitor nimesulide (3 mg/kg, s.c.), the NO donor sodium nitroprusside (4 mg/kg, i.v.) or the iNOS inhibitor dexamethasone (3 mg./kg, i.p.) at macroscopic level and reversed by Indo or Dex at microscopic level. Increased peroxidase activity -index of tissue neutrophil infiltration- in the distal ileum of LPS-treated rats was decreased by alpha-MSH and this effect was reversed by pretreatment with Indo. In conclusion, the neuropeptide alpha-MSH has a beneficial effect on endotoxin-induced distal intestinal lesions by a mechanism which probably involves nitric oxide and COX-1 derived prostaglandins.

Role of capsaicin-sensitive nerves in gastric and hepatic injury induced by cold-restraint stress.

The role of capsaicin-sensitive afferent fibers on cold-restraint stress-induced gastric and hepatic injury was examined at the macroscopic and ultrastructural levels. Wistar albino rats were treated with capsaicin either locally (intragastric, perivagal, and periceliac) or systemically (neonatal, intraperitoneal). Perineural and neonatal treatment with capsaicin was used to denervate afferent fibers, while intragastric capsaicin treatment would have activated mucosal afferent fibers just before the stress exposure. Capsaicin decreased significantly the formation of macroscopic gastric lesions caused by stress in all treatment groups. At the electron microscopic level, however, denervation of vagal afferent fibers with capsaicin was most effective in prevention of cellular injury in gastric mucosa. In the liver, systemic denervation of afferent fibers completely inhibited stress-induced cellular damage, while denervation of afferent fibers in vagus and splanchnic nerve was partially effective. Central neural pathways sensitive to capsaicin may mediate formation of both gastric and hepatic injury resulting from stress.

The effect of alpha-melanocyte stimulating hormone on colonic inflammation in the rat.

The effect of alpha-melanocyte stimulating hormone (alpha-MSH) on colonic inflammation in the rat. In this study, we investigated the effects of alpha-MSH administration on trinitrobenzene sulfonic acid-induced colitis and the role of nitric oxide and prostaglandins in this response. alpha-MSH treatment (25 microg/rat, intraperitoneally; twice daily for 3 days) reduced the colonic macroscopic lesions compared to untreated ones in both acute and chronic colitis groups. This effect was reversed by pretreatment with the nitric oxide donor, sodium NP (4 mg/kg, intravenously) or cyclooxygenase-1 selective antagonist indomethacin (5 mg/kg, subcutaneously) in the acute group and with the cyclooxygenase-2 selective antagonist nimesulide (3 mg/kg, subcutaneously) in the chronic group. alpha-MSH had no effect on colonic wet weight and myeloperoxidase activity compared to the untreated colitis group. However, protein oxidation was markedly elevated in the alpha-MSH-treated group compared to untreated ones. Nitroprusside and indomethacin reversed the effect of alpha-MSH on macroscopic lesions in the acute groups, whereas nimesulide showed a similar effect in the chronic group. In conclusion, the results of our study show a protective role of alpha-MSH on colonic lesions which partially involves nitric oxide and prostaglandins.