[Show abstract][Hide abstract] ABSTRACT: Scaffold-based bone defect reconstructions still face many challenges due to their inadequate osteoinductive and osteoconductive properties. Various biocompatible and biodegradable scaffolds, combined with proper cell type and biochemical signal molecules, have attracted significant interest in hard tissue engineering approaches. In the present study, we have evaluated the effects of boron incorporation into poly-(lactide-co-glycolide-acid) (PLGA) scaffolds, with or without rat adipose-derived stem cells (rADSCs), on bone healing in vitro and in vivo. The results revealed that boron containing scaffolds increased in vitro proliferation, attachment and calcium mineralization of rADSCs. In addition, boron containing scaffold application resulted in increased bone regeneration by enhancing osteocalcin, VEGF and collagen type I protein levels in a femur defect model. Bone mineralization density (BMD) and computed tomography (CT) analysis proved that boron incorporated scaffold administration increased the healing rate of bone defects. Transplanting stem cells into boron containing scaffolds was found to further improve bone-related outcomes compared to control groups. Additional studies are highly warranted for the investigation of the mechanical properties of these scaffolds in order to address their potential use in clinics. The study proposes that boron serves as a promising innovative approach in manufacturing scaffold systems for functional bone tissue engineering.
Materials Science and Engineering C 11/2014; 44:246–253. · 2.40 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: ABSTRACT Aim: The aim of this study was to research the effects of pregabalin on experimentally induced peripheral nerve crush injuries in rats. Material and method: Forty-two adult female Wistar albino rats were divided into seven groups: 1(st) group: healthy; 2(nd) group: axonotmesis control; 3(rd) group: anastomosis control; 4(th) group: axonotmesis+30 mg/kg of pregabalin; 5(th) group: axonotmesis+60 mg/kg of pregabalin; 6(th) group: anastomosis+30 mg/kg of pregabalin; 7(th) group: anastomosis+60 mg/kg of pregabalin. Evaluation of the sciatic functional index (SFI) was performed one day before and on days 7, 14, 21, and 28 following surgery. The right sciatic nerves of all animals were examined histopathologically and molecularly. Results: After 28 days post-injury, the histopathological regeneration in peripheral nerve injuries for pregabalin 30 mg/kg treated groups was significantly better than that of the control groups. Also the SFI increases and TGF-β gene expression up-regulation were significantly better in pregabalin 30 mg/kg treated groups. Conclusion: The histopathological, functional and molecular data suggest that pregabalin 30 mg/kg treatment in axonotmesis and anostomosis groups improves nerve regeneration and increases SFI in peripheral nerve injuries by activating antiinflammatory cytokine TGF-β1.
The International journal of neuroscience. 10/2014;
[Show abstract][Hide abstract] ABSTRACT: Sepsis and sepsis-related acute lung injuries (ALIs) are one of the main causes of death among hospitalized patients. Renin-angiotensin-aldosterone system (RAAS) has been reported to have role in sepsis. However, there is no study on aliskiren, a renin inhibitor, on sepsis-induced ALI. We aimed to investigate the potential protective effects of aliskiren in a model of cecal ligation and puncture (CLP)-induced lung injury. The rats were separated into five groups: sham, CLP, CLP + aliskiren 50 mg/kg (per orem (p.o.)), CLP + aliskiren 100 mg/kg (p.o.), and sham + aliskiren 100 mg/kg (p.o.). CLP model was applied via ligation of cecum and two punctures. After experiment, biochemical, molecular, and pathologic examinations were performed on lung and serum samples of rats. In our study, sepsis decreased superoxide dismutase (SOD) and glutathione (GSH) and increased malondialdehyde (MDA) in lung tissues of rats while aliskiren increased the SOD and GSH and decreased MDA. Also, sepsis caused a significant increase in pro-inflammatory cytokine levels (TNF-α, IL-1β, and IL-6) while aliskiren administration decreased these cytokines. Also, aliskiren administration at high dose protected lungs in pathologic evaluation. As a result of RAAS inhibition, aliskiren caused a decrease in serum angiotensin II level and increase in serum renin level. In light of these observations, we can suggest that the therapeutic administration of aliskiren prevented oxidative stress changes and cytokine changes and also protected lung tissues during CLP-induced sepsis by changing status of RAAS.
Naunyn-Schmiedeberg's archives of pharmacology. 07/2014;
[Show abstract][Hide abstract] ABSTRACT: ABSTRACT Background: Intestinal ischemia reperfusion (IR) is associated with morbidity and mortality. We first examined the role of levosimendan in the protection of intestine after mesenteric IR. Methods: The rats were divided into six groups: (1) Control group; (2) Levosimendan group; (3) Ischemia group (60 min of occlusion); (4) IR group (60 min of occlusion and then 60 min reperfusion); (5) IR + 1 mg/kg levosimendan group: Levosimendan was given intraperitonally 30 min prior to the ischemia; (6) IR + 2 mg/kg levosimendan group. Results: The levels of TNF-α, IL-6, and IL-1β were found to have increased in the IR group. The serum levels of TNF-α, IL-6, and IL-1β were found to have decreased as a result of the administration of both doses of levosimendan in the IR. Relative TNF-α and NFκB mRNA levels was decreased by administration of both doses of levosimendan in the IR. SOD activity and GSH levels for IR group were lower than, and 8-ISO levels were higher than, those of the sham-operated rat and ischemia alone group. Conclusions: Both doses of levosimendan had preventive effects on the alterations that occurred in the intestinal tissues after IR. Levosimendan administration attenuated in reperfusion injury of intestine and consequently protects intestinal mucosa and oxidant-antioxidant balance of ileum.
Journal of Investigative Surgery 08/2013; · 1.32 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The aim of this study was: (1) to investigate possible role for 5-HT7 receptors in carrageenan induced inflammatory paw oedema in rats; (2) to determine the presence of 5-HT7 receptors in rat paw tissue; (3) to observe the effects of 5-HT7 receptor agonist and antagonist administration on inflammation; and (4) to determine a unique mechanism for inflammatory processes via 5-HT7 receptors. Effects of 5-HT7 receptor agonist, antagonist and indomethacin were investigated in carrageenan induced paw oedema in rats. Blood and tissue samples were collected and evaluated biochemically for serum cytokine levels, tissue oxidant-antioxidant balance and histopathologically for inflammatory cell accumulation. We performed Real Time PCR analyses for tissue 5-HT7 receptor and COX mRNA expressions. The 5-HT7 receptor agonist AS-19 exerted significant anti-inflammatory effect both alone and in combination with indomethacin. Antagonist, SB269970, did not affect inflammation alone but decreased the effects of agonist when co-administered. 5-HT7 mRNA levels were higher in the carrageenan group than healthy control. Carrageenan+indometacin group decreased the mRNA expression of 5-HT7 when compared to carrageenan group. While agonist administration decreased 5-HT7 mRNA expression when compared to carrageenan group. Agonist decreased paw COX expression. Agonist also decreased serum cytokine levels and tissue oxidative stress. In conclusion, this study demonstrated for the first time that 5-HT7 receptors are expressed in rat paw tissue and that this expression responds to inflammatory stimuli. The 5-HT7 receptor may be a promising new therapeutic target for prevention of inflammation and inflammatory disorders and may also provide a new glimpse into inflammation pathophysiology.
European journal of pharmacology 06/2013; · 2.59 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Sepsis is a complex pathophysiological event involving metabolic acidosis, systemic inflammatory response syndrome, tissue damage and multiple organ dysfunction syndrome. Although many new mechanisms are being investigated to enlighten the pathophysiology of sepsis, there is no effective treatment protocol yet. Presence of 5-HT7 receptors in immune tissues prompted us to hypothesize that these receptors have roles in inflammation and sepsis. We investigated the effects of 5-HT7 receptor agonists and antagonists on serum cytokine levels, lung oxidative stress, lung histopathology, nuclear factor κB (NF-κB) positivity and lung 5-HT7 receptor density in cecal ligation and puncture (CLP) induced sepsis model of rats. Agonist administration to septic rats increased survival time; decreased serum cytokine response against CLP; decreased oxidative stress and increased antioxidant system in lungs; decreased the tissue NF-κB immunopositivity, which is high in septic rats; and decreased the sepsis-induced lung injury. In septic rats, as a result of high inflammatory response, 5-HT7 receptor expression in lungs increased significantly and agonist administration, which decreased inflammatory response and related mortality, decreased the 5-HT7 receptor expression. In conclusion, all these data suggest that stimulation of 5-HT7 receptors may be a new therapeutic target for prevention of impaired inflammatory response related lung injury and mortality.
[Show abstract][Hide abstract] ABSTRACT: Paracetamol was shown to induce hepatotoxicity or more severe fatal acute hepatic damage. Agomelatine, commonly known as melatonin receptor agonist, is a new antidepressant, which resynchronizes circadian rhythms with subjective and objective improvements in sleep quality and architecture, as melatonin does. In the present study, it was aimed to evaluate the hepatoprotective activity of agomelatine on paracetamol-induced hepatotoxicity and to understand the relationship between the hepatoprotective mechanism of agomelatine and antioxidant system and proinflammatory cytokines. A total of 42 rats were divided into 7 groups as each composed of 6 rats: (1) intact, (2) 40 mg/kg agomelatine, (3) 140 mg/kg N-acetylcysteine (NAC), (4) 2 g/kg paracetamol, (5) 2 g/kg paracetamol + 140 mg/kg NAC, (6) 2 g/kg paracetamol + 20 mg/kg agomelatine, and (7) 2 g/kg paracetamol + 40 mg/kg agomelatine groups. Paracetamol-induced hepatotoxicity was applied and liver and blood samples were analyzed histopathologically and biochemically. There were statistically significant increases in the activities of aspartate aminotransferase, alanine aminotransferase, levels of tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6) and 8-iso-prostane, and decreases in the activity of superoxide dismutase and level of glutathione in the group treated with paracetamol. Administration of agomelatine and NAC separately reversed these changes significantly. In conclusion, agomelatine administration protects liver cells from paracetamol-induced hepatotoxicity via antioxidant activity and reduced proinflammatory cytokines, such as TNF-α and IL-6.
Human & Experimental Toxicology 04/2013; · 1.31 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Sepsis is the systemic response of an organism against microorganisms and toxins. Lithium is a therapeutic agent used for bipolar disorder and neurodegenerative disease, and it exerts pleiotropic effects on various cellular processes. The present study aimed to determine the effect of lithium on cecal ligation and puncture (CLP)-induced tissue injury in the lungs, by inhibiting the pro-inflammatory cytokine response, and the generation of reactive oxygen species (ROS) triggered by polymicrobial sepsis. Five groups of 20 rats each were used: 1) sham-operated control group; 2) CLP group; 3) 50mg/kg lithium-treated control healthy group; 4) 25mg/kg lithium-treated CLP group; and 5) 50mg/kg lithium-treated CLP group. A CLP polymicrobial sepsis model was applied to the rats. All rat groups were killed 16h later, and lung and blood samples were analyzed histopathologically and biochemically. The 25 and 50mg/kg of lithium decreased the level of interleukin-1 beta (IL-1β), interleukin-6 (IL-6), and the tumor necrosis factor-α (TNF-α) in the serum, and the 8-iso-prostaglandin F2α (8-ISO) level in lung tissue. The lithium also increased the activity of superoxide dismutase (SOD) and the total levels of glutathione (GSH) in the lung tissues of rats. The histopathological scores and examinations were in accordance with the biochemical results, and revealed significant differences in the inflammation scores between the sepsis group and the other groups. The CLP+lithium 50mg/kg group had the lowest inflammation score among the CLP groups. Our results indicated that the therapeutic administration of lithium prevented oxidative stress changes and cytokine changes, and also protected vital tissues.
International immunopharmacology 03/2013; · 2.21 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Background: Urinary calculi are a common and severe problem, which are formed by urolithiasis or by the formation of calcium oxalate (CaOx) crystals in the kidneys. Many treatment options such as drugs, various herbal preparations, surgical removal of the stones, and extracorporeal shock wave lithotripsy have been applied for this condition. The aim of this study is to assess the effects of the drug amlodipine in an experimentally induced urolithiasis rat model. Materials and methods: The effect of 5 mg/kg amlodipine was studied in rats that were first treated with 1% ethylene glycol and 1% ammonium chloride for 21 days to induce urolithiasis. The weight differences and the levels of calcium, magnesium, and phosphate were measured in serum and urine. In addition, urine CaOx level was defined and histopathological analyses were performed on the kidneys. Results: Urolithiasis caused a significant increase in both serum and urine parameters compared with healthy rats. Urolithiasis plus amlodipine administration increased the levels of these same parameters. Urine CaOx level was high in urolithiasis rats and was also increased by urolithiasis plus amlodipine administration. The weight of the rats decreased in the urolithiasis plus amlodipine group when compared with the urolithiasis group. Histopathological examinations revealed extensive intratubular crystal depositions and degenerative tubular structures in the urolithiasis group and the amlodipine treatment group. Conclusion: We showed that amlodipine may increase susceptibility to urolithiasis by raising hyperoxaluria and hypercalciuria. Further studies should be performed to elucidate the urolithiasis activity of amlodipine and to confirm the data.
[Show abstract][Hide abstract] ABSTRACT: Levosimendan (LEVO) is a new calcium sensitizer with positive inotropic and vasodilating properties that represents a new pharmacological class of inotropic drugs that stimulate elevated cardiac output. The purpose of this study was to examine anti-inflammatory effect and antioxidant activity of LEVO in a carrageenan (CAR)-induced inflammatory paw oedema rat model. The CAR-induced rat groups received LEVO 1, 2 and 3 mg/kg by intraperitonally and indomethacin (IND) 25 mg/kg by oral gavage. LEVO inhibited CAR-induced paw oedema and suppressed the production of TNF-α, IL-1 and IL-6 at doses of 2 and 3 mg/kg. In contrast to CAR-injected paws, 2 and 3 mg/kg doses of LEVO and IND increased superoxide dismutase (SOD) activity and also both doses of LEVO, and IND decreased the 8-isoprostaglandin F2α (8-ISO) level. A 2 mg/kg dose of LEVO produced 39%, 46%, 61% and 64.7% anti-inflammatory effects (p < 0.0001) for the 1st, 2nd, 3rd and 4th hours, respectively. Other results of our current study have shown that SOD and glutathione for CAR-injected groups were lower, and 8-ISO level was higher than those for the healthy rat group. LEVO may be provided as a pharmacological agent in the prevention or treatment of diseases in which acute or chronic inflammation occurs based on a pathogenic factor.
[Show abstract][Hide abstract] ABSTRACT: The presence of liver disease in patients with progressively worsening insulin resistance may not be recognized until patients develop manifestations of the metabolic syndrome such as diabetes, hypertension, hyperlipidemia, and vascular disease. It was aimed to investigate whether three angiotensin II type 1 receptor antagonists (ARBs) (olmesartan, losartan, and valsartan) had preventive effect against hepatic fibrosis and this was a common characteristic among ARBs. In current study, 25 adult male rats were used and divided into five groups: the non-diabetic healthy group, alloxan induced diabetic (AID) control group, AID losartan group, AID valsartan group and AID olmesartan group. According to numerical density of hepatocytes, significant difference was found between the non-diabetic healthy group and diabetic control group. All treatments groups were significant when compared to diabetic control group. In diabetic control group it was examined swelling, irregular cristae arrangement in some of mitochondria. It was also determined mitochondria membrane degeneration in some areas of section profiles. In diabetic rats treated with losartan group, there were necrotic hepatocytes. In diabetic rats treated with valsartan group, predominantly, findings were similar to losartan group. In diabetic rats treated with olmesertan group, plates of hepatocytes were quite regular. There were hardly necrotic cells. Not only other organelles such as RER, SER and lysosom but also mitochondrial structures had normal appearance. In the diabetic control group electron microscopy revealed edema in both the cytoplasm and perinuclear area and the nuclear membranes appeared damaged. In conclusion, it was established that the most protective ARB the liver in diabetic rats was olmesartan, followed by losartan.
Journal of molecular histology 08/2012; · 1.75 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The aim of this study was to determine the effects of diabetes mellitus, ovarian aging, ovarian aging plus diabetes mellitus, and the oxidative stress generated by these conditions on the lungs of rats, using histopatological and biochemical parameters. In the diabetic group, some abnormalities like bronchial hyperplasia, edema, haemorrhage, pulmonary capillary dilatation, breakdown of alveoli, mononuclear inflammatory cells, and moderate immunoreactivity were observed. Although, the results obtained from the ovariectomy group were similar to those of the diabetic group, haemorrhagic area and an increase in apoptotic cell density were observed more in this group compared to the diabetic group. In the last group, both immunoreactivity rate and the degree of abnormal structure were more remarkable compared to the other groups. Our biochemical results confirmed the histological findings. Conclusively, increase in the reactive oxygen species (ROS) levels of the cell, regardless of whatever reason, may lead to many other functional failures as well produce some disease conditions. Our results suggested that oxidative load increased in rats with ovariectomy-induced menopause with or without diabetes; however, enzymatic free radical defense mechanisms were damaged in the diabetic rats. The results also suggested that the antioxidant ability of the female sex hormone acts as a protective factor against diabetes.
African journal of pharmacy and pharmacology 07/2012; 6(27):1989-2010. · 0.84 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The protective effects of Panax ginseng (PG) on gentamicin sulphate (GS) induced acute nephrotoxicity were investigated in rats. A total of 32 adult Sprague-Dawley rats were randomly divided into 4 equal groups and treated by intraperitoneous route for 10 days with: 0.5 mL of isotonic saline (group C), GS 100 mg/kg/day (group GS), co treatment PG (100 and 200 mg/kg/day) plus GS (100 mg/kg/day). After the last injection, kidney markers (urea, creatinine and blood urea nitrogen-BUN) and hepatic markers (aspartate aminotransferase-AST, alanine aminotransferase-ALT, gama glutamil transferase-GGT), and biochemical parameters were analyzed using diagnostic kits. Also, kidney changes were evaluated by immunohistochemical and stereological methods. GS treatment induced significant elevation (P < 0.05) in kidney and hepatic markers, most of biochemical parameters, and Bax immunoreactivity as well. However, co treatments with both doses of PG (100 and 200 mg/kg/day) significantly alleviated (P < 0.05) the GS-induced elevations and have partially protected rats from nephrotoxicity (reduction of kidney damage, and of urea, creatinine and BUN concentrations, and of apoptotic index). Both biochemical results and immunohistochemical evidence showed that administration of PG reduced the gentamicin-induced nephrotoxicity.
Journal of molecular histology 04/2012; 43(5):603-13. · 1.75 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The objective of this study was to determine the value of time-dependent ischemia-modified ghrelin in mesenteric ischemia. The authors investigated whether or not there is changes in plasma ghrelin levels in the acute period in a rat model of mesenteric ischemia were time-related. 42 mature male rats were divided into seven groups: one control and six ischemia groups. In the ischemia groups, following laparotomy the superior mesenteric artery (SMA) was ligated using a 2/0 silk suture, and blood samples were taken at 30, 60, 90, 120, 150 and 180 min. Plasma ghrelin levels in all the ischemia groups were significantly higher compared to the control group. In addition, the highest level of ghrelin was observed at 180 min. In our current study we have shown a direct increase in ghrelin in cases of acute mesenteric ischemia (AMI). This is a result of ghrelin's protective effect against ischema/reperfusion (I/R) damage on the intestines, as in most of the other organs. With these characteristics, ghrelin can be easily applied in AMI and appears to be a prognosis parameter that can be used in clinics and needs no technological equipment or experience.
African journal of pharmacy and pharmacology 04/2012; 66(13):1017-1021. · 0.84 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To evaluate biochemically and histopathologically the effects of Nigella sativa (NS) in experimental ischemia and ischemia/reperfusion (I/R) injury in rat ovaries.
Thirty-six female rats were divided into 6 groups: group I = sham operation; group II = 500 mg/kg NS + sham operation; group III = bilateral ovarian ischemia; group IV = 500 mg/kg NS + ischemia; group V = 3-hour period of ischemia + 3-hour reperfusion, and group VI: 3-hour period of ischemia + 500 mg/kg NS 2.5 h after the induction of ischemia + 3-hour reperfusion. At the end of ischemia, the bilateral vascular clips were removed, and 3-hour reperfusion was continued. IL-1β, IL-6, and TNF-α cytokine levels in serum, and superoxide dismutase (SOD), myeloperoxidase (MPO), glutathione (GSH), and malondialdehyde (MDA) levels were determined.
I/R increased the MDA level and MPO activity while significantly decreasing the SOD activity and GSH level when compared to the sham. The 500-mg/kg dose of NS before I/R reversed the trend in MDA levels, MPO activity, SOD activity, and GSH levels. Ischemia and I/R increased the serum levels of IL-1β, IL-6, and TNF-α, while the administration of NS decreased the serum levels of these cytokines.
The administration of NS is effective in reversing tissue damage induced by ischemia and/or I/R in ovaries.
Gynecologic and Obstetric Investigation 03/2012; 74(1):41-9. · 1.10 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: In this study, the effects of lacidipine (LAC), ramipril (RAM), and valsartan (VAL) on biochemical and histopathologic changes in heart tissue were studied in rats with isoproterenol-induced (ISO-induced) myocardial infarction (MI). LAC, RAM, and VAL had been administered via oral gavage at 3, 3, and 30 mg/kg doses, respectively, once per day during a 30-day time period. On days 29 and 30, the drug treatment group and the control group (with the exception of the intact control group, in which no medications were given, and ISO was not administered) were administered 180 mg/kg ISO subcutaneously over an interval of 24 h. After this period, the hearts of the rats were removed and processed for biochemical and histopathologic studies. The antioxidant parameters superoxide dismutase (SOD), catalase (CAT), and malondialdehyde (MDA) were estimated. A diagnosis of MI was confirmed with antioxidant parameters and histopathologic findings. In MI control groups, histopathologic indicators were found to be statistically higher than those in drug groups; an increase in histopathologic indicators of MI correlates with significant decreases in SOD and CAT levels, and an increase in MDA level. Histopathologic grades of MI indicators were significantly higher in MI group that did not receive any cardioprotective medications in comparison with MI groups that received LAC, RAM, and VAL. Each of the three medications favorably modulated most of the biochemical and histopathologic parameters observed. No significant difference existed with regard to any of the estimated parameters in the rat groups that received medications without MI induction. In conclusion, results indicate that LAC, RAM, and VAL significantly reduced myocardial injury and emphasize the cardioprotective nature of these agents.
[Show abstract][Hide abstract] ABSTRACT: Tianeptine is an anti-depressant drug that also has an anti-ulcer activity. In this study, it was investigated whether or not α2-adrenoreceptors have a role in the anti-ulcer effect mechanism of tianeptine. Furthermore, we investigated both intact and adrenalectomized rats to determine whether or not the anti-ulcer activity of tianeptine is related to adrenal gland hormones involved in this mechanism. In all rats, 25 mg/kg indomethacin produced gastric ulceration. Tianeptine was administered to the indomethacin-induced ulcers in the rats at different doses. Yohimbine, selective α2-receptor blocker, was given (10 mg/kg) to some rats (adrenalectomized 6 groups and intact 4 groups), for blockage of the α2-receptor. Tianeptine showed antiulcer effects of 59.6-81.6% in all animals. The results of this study show that tianeptine caused a significant anti-ulcer activity in both adrenalectomized and intact rats. Tianeptine does not have an anti-ulcer effect in rats which have been given yohimbine. Thus, the adrenal gland hormones do not have a direct effect on the anti-ulcer activity of tianeptine. This drug may be directly related to the α2-adrenoreceptors. Moreover, the anti-ulcer effect shows an increase in parallel with increasing dose. This property of tianeptine could make it suitable for use in the treatment of both depression and peptic ulcer patients. Sıçanlarda Tianeptinin Antiülser Etki Mekanizmasında α 2 -Adrenoreseptörlerin Direkt Etkisi Özet Tianeptin antiülser aktiviteye de sahip antidepresan bir ilaçtır. Bu çalışmada tianeptinin antiülser mekanizmasında α2 reseptörlerin rollerinin olup olmadığı araştırılmıştır. Ayrıca, tianeptinin antiülser mekanizmasında adrenal bez hormonları ile ilişkili olup olmadığını hem sağlıklı hem de adrenalektomi yapılan ratlarda incelenmiştir. 25 mg/kg indometazin tüm ratlarda gastrik ülserasyon meydana getirdi. İndometazinle indüklenerek ülser oluşturulan ratlara farklı dozlarda tianeptin uygulanmıştır. Seçici bir α2-reseptör blokörü olan yohimbin (10 mg/kg) reseptör blokajı için hayvanların bir kısmına (adrenalektomili 6 grup ve sağlam 4 grup) verilmiştir. Tianeptin tüm hayvanlarda %59.6-81.6 anti-ülser etki meydana getirdiği tespit edilmiştir. Bu sonuçlar göstermektedir ki tianeptin hem sağlıklı hem de adrenalektomili hayvanlarda önemli bir anti ülser etki meydana getirdiği gözlenmiştir. Yohimbin verilen hayvanlarda ise antiülser etki oluşturmadığı tespit edilmiştir. Bu yüzden, tianeptinin anti ülser etki mekanizmasında adrenal bez hormonları direk bir role sahip olmadığı gözlenmiştir. Bu ilaç α2-reseptörlerle direk alakalı olabilir. Ayrıca anti ülser etki doza parallel olarak doz arttıkça artmaktadır. Tianeptinin bu özelliği onu hem depresyonlu hem de gastrik ülserli hastaların tedavisinde kullanıma uygun hale getirebilir.
Kafkas Üniversitesi Veteriner Fakültesi Dergisi 01/2012; 18:713-718. · 0.46 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: We aimed to investigate how Diabetes Mellitus (DM) affects myeloperoxidase activity, antioxidant status, and lipid peroxidation using biochemical approaches in heart, liver, and lung and serum cytokine analyses, such as interleukin-6 (IL-6) and tumor necrosis factor α (TNF-α) in rat with sepsis induced by a cecal ligation and puncture-induced (CLP) sepsis. The rats were divided into four groups: control group, diabetic group, sepsis group, and diabetic+sepsis group. DM was induced in the male Wistar albino rats by administration of alloxan. Polymicrobial sepsis was induced by cecal ligation and two-hole puncture. After alloxan administration, all groups of rats were allowed to recover for 1 month. CLP model was applied after 1 month recovery to group 3 and 4. IL-6 and TNF-α, were measured. Effects of antioxidant defenses on the DM and/or sepsis process, the antioxidant levels superoxide dismutase (SOD), catalase (CAT), glutathione (GSH) were evaluated in heart, lung and liver tissues. The oxidant levels, such as lipid peroxidation (LPO) and myeloperoxidase (MPO) levels were also evaluated in tissues. We demonstrated DM to augment the level of oxidant and proinflammatory cytokines in lung, liver, and heart and also to exacerbate oxidative injury as assessed by increased LPO and MPO, and decreased GSH and SOD levels in a sepsis model. DM increased levels of proinflammatory cytokines while DM also resulted in significantly increased levels of proinflammatory cytokines following CLP. DM-increased plasma proinflammatory cytokines levels correlated positively with tissue oxidant levels, such as MPO and LPO levels in a rat abdominal sepsis model, based on CLP, which resulted in the exacerbation of oxidative organs injury.
[Show abstract][Hide abstract] ABSTRACT: Antidepresanların Epilepside Kullanım Alanları Özet Epilepsi beyindeki sinir hücrelerinin olağandışı, ani, aşırı ve anormal bir elekro-kimyasal boşalma yapması sonucu kısa süreli ortaya çıkan nörolojik bir hastalıktır. Epilepsi ile komorbit olarak ortaya çıkan depresyon epilepsisi olan hastaların yaşam kalitesini olumsuz etkileyebilir. Epilepsisi ve depresyo-nu olan insanlar depresyonu olmayan epilepsili hastalara nazaran, antiepilep-tik ilaçların yan etkilerine daha çok maruz kaldıklarından dolayı daha yaygın bir şekilde ilaca karşı direnç gösterirler. Epilepsideki duygu durum bozukluk-larının tedavisinde antiepileptik ve psikoaktif ilaçlar daha sık birlikte kullanıl-maya başlanmıştır. Farmakokinetik etkileşimler, ilacın emilim, dağılım, biyot-ransformasyon ve atılım gibi çeşitli aşamalarında meydana gelebilir. Epilep-sili hastalarda artmış depresyon riski mi yoksa depresyonlu hastalarda art-mış epilepsi riski mi sorusuna güncel bilgiler ışığında henüz net bir cevap ve-rilememiştir. Bu nedenle epilepsili hastalarda depresyon tedavisi önemle üze-rinde durulması gereken bir konu olarak karşımıza çıkmaktadır. Epilepsili has-talarda depresyon tedavisi yaparken ilaç seçiminde oldukça dikkatli olunma-lı, doz ayarı yapılırken küçük dozlarla başlayıp optimal doz titizlikle seçme-lidir. Son olarak antidepresanlar ile antiepileptik ilaçların gerek etki yerle-ri gerekse metabolizmaya uğradıkları yerler bakımında benzer oldukları için farmakodinamik ve farmakokinetik etkileşimlerinde çok dikkatli davranılma-sı gerekmektedir.
Journal of Clinical and Analytical Medicine. 01/2012;