Melatonin protects against pancreaticobiliary inflammation and associated remote organ injury in rats: role of neutrophils.
ABSTRACT Although the role of oxidative stress in acute pancreatitis (AP) has been studied in several animal models, little data are available regarding AP induced by pancreatic duct obstruction. We characterized the protective effects of melatonin on pancreaticobiliary inflammation and associated remote organ injury. In Sprague-Dawley rats, either the common pancreaticobiliary duct (PBDL; n = 28) or bile duct (BDL; n = 28) was ligated or a sham operation was applied (n = 14). Either melatonin (10 mg/kg) or vehicle (saline; 1 mL/kg) was administered intraperitoneally (i.p.) immediately before the surgery and twice a day until the rats were decapitated at 6 or 72 h. The pancreas, liver, kidneys and lungs were removed and tissue samples were stored for the determination of malondialdehyde (MDA) and glutathione (GSH) levels and myelopreoxidase activity. The results demonstrate that pathogenesis of acute obstructive pancreatitis involves not only the oxidative damage of the pancreatic and hepatic tissues, as assessed by increased MDA and reduced GSH levels, but the lungs and kidneys are also challenged by oxidant injury. Similarly, hepatic oxidative injury caused by cholestasis was also accompanied by pulmonary, renal and even pancreatic damage. The biochemical findings were also verified histologically. Melatonin, probably because of its free-radical scavenging and antioxidant activity, which involves an inhibitory effect on tissue neutrophil infiltration, protected all the affected tissues.
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ABSTRACT: Cirrhotic patients exhibit disturbed melatonin homeostasis, which may lead to sleep disturbances, but an influence on the hepatic encephalopathy has not been elucidated. Aim. In the present study, the association of melatonin levels in serum and ascitic fluid and ammonia concentration related to the intensity of hepatic encephalopathy (HE) was investigated. Material and Methods. The study included 90 alcoholic patients with hepatic encephalopathy and 30 healthy volunteers (C). Patients were divided in three groups according to 0-4 West-Haven Score: HE(1) (n = 28), HE(2) (n = 30), and HE(3) (n = 32). Melatonin was measured by radioimmune assay. Results. In fasting patients with hepatic encephalopathy we noted higher melatonin serum levels [pg/mL] than in healthy subjects groups: C-11.3 ± 3.9, HE(1) - 34.3 ± 12.2 (P < 0.01), HE(2)-54.8 ± 23.9, and HE(3)-119.8 ± 96.4 (P < 0.001). No correlation between melatonin and ammonia levels was found. Melatonin was detected in ascetic fluid in 24 patients of group HE(2) and 27 patients of group HE(2) of hepatic encephalopathy. Conclusions. Our results suggest that high blood levels of melatonin in cirrhotic liver patients may account for some of the clinical manifestations of hepatic encephalopathy, for example, daytime sleepiness, fatigue.Gastroenterology Research and Practice 01/2012; 2012:510764. · 0.98 Impact Factor
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ABSTRACT: SüleymanDemirel Üniversitesi TIP FAKÜLTESİ DERGİSİ: 2005 Eylül; 12(3) Ratlarda kadmiyumun pankreasa etkileri Osman Gökalp, Mehmet Kaya Özer,Ahmet Koyu, Ekrem Çiçek, Recep Sütçü, Ahmet Koçak, Sebahat Özdem, Onur Aktürk Özet Kadmiyum pekçok organ üzerinde zararlı etkileri olan bir metal olup, diğer bazı metaller gibi pankreatiteyol açabilmektedir. Bu çalışmada, ratlarda kadmiyumun pankreas üzerindeki zararlı etkilerini araştırmayı amaçladık. Çalışma grupları, kontrol ve kadmiyum grupları şeklinde düzenlendi. Kadmiyum grubuna içme suyu ile 30 gün boyunca 15 ppm dozunda kadmiyum içirildi. 30. günün sonunda, üretan anestezisi altında ratlardan kan örnekleri alındı. Alınan serum örneklerinde, amilaz ve lipaz aktiviteleri ölçüldü. Kadmiyum uygulanan grup kontrol grubuyla karşılaştırıldığında, kadmium uygulanan grubun kan kadmiyum seviyelerinde anlamlı bir artışın meydana geldiği (P0.05). Histopatolojik incelmede ise, kadmiyum uygulanan grubun pankreas preperatlarında kanama odaklarının ve bağ dokusu artışının olduğu tespit edildi. Sonuçta elde edilen bulgular, uzun süre içme suyu ile düşük doz kadmiyum verilen ratlarda biyokimyasal olarak aktif pankreatitin gelişmediği, ancak histopatolojik incelemede göreceli olarak hafif patolojik değişikliklerin olabileceğini düşündürdü. Anahtar kelimeler: Kadmiyum, pankreatit, amilaz, lipaz. Abstract Effects of cadmıum on pancreas ın rats Cadmium is a metal which causes toxic effects in various organs. In some cases, several metals like zinc cause acute pancreatitis. Therefore, we aimed to investigate possible adverse effects of cadmium in rat pancreas. Study groups were designed as control and cadmium groups. Cadmium groups were given 15 ppm cadmium chloride for 30 days via drinking water. In the end of the study, blood samples were taken under urethane anesthesia. In each sample, serum amylase and lipase enzyme activities were measured.When compared with control group, both serum lipase and amylase enzyme activities were increased in cadmium group but this was not significant. Furthermore, in cadmium group there were some congestion focuses and increase in connective tissue. We have concluded that cadmium seems not to lead biochemically active pancreas damage, however some mild histopathological changes can be seen when cadmium is administered to rats at this dose level. Key words: Cadmium ,pancreatitis, amylase, lipase.SDÜ Tıp Fakültesi Dergisi; Vol 12, No 3 (2005).