Emre Karakus

Ataturk University, Kalikala, Erzurum, Turkey

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Publications (34)57.92 Total impact

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    ABSTRACT: The opioid and non-opioid types of stress-induced analgesia have been well defined. One of the non-opioid type involve the endocannabinoid system. We previously reported that the spinal serotonin 7 receptor (5-HT7) blockers inhibit both morphine and cannabinoid-induced analgesia, thus we hypothesized that descending serotonergic pathways-spinal 5-HT7 receptor loop might contribute to stress-induced analgesia. Stress-induced analgesia were induced with warm (32°C) or cold (20°C) water swim stress in male Balb-C mice. The effects of intrathecal injection of a selective 5-HT7 receptor antagonist, SB 269970, of the denervation of serotonergic neurons by intrathecal administration of 5,7-dihydroxytryptamine (5,7-DHT) and of lesions of the dorsolateral funiculus on opioid and non-opioid type stress-induced analgesia were evaluated with the tail-flick and hot plate tests. The expression of 5-HT7 receptors mRNA in the dorsal lumbar region of spinal cord were analyzed by RT-PCR following spinal serotonin depletion or dorsolateral funiculus lesion. The effects of the selective 5-HT7 receptor agonists LP 44 and AS 19 were tested on nociception. Intrathecal SB 269970 blocked both opioid and non-opioid type stress-induced analgesia. Dorsolateral funiculus lesion or denervation of the spinal serotonergic neurons resulted in a marked decrease in 5-HT7 receptor expression in the dorsal lumbar spinal cord, accompanied by inhibition of opioid and non-opioid type stress-induced analgesia. However, the systemic or intrathecal LP 44 and AS 19 alone didn't produce analgesia in unstressed mice. These results indicate that descending serotonergic pathways and the spinal 5-HT7 receptor loop play a crucial role in mediating both opioid and non-opioid type stress-induced analgesia. Copyright © 2015. Published by Elsevier B.V.
    European journal of pharmacology 04/2015; DOI:10.1016/j.ejphar.2015.04.020 · 2.68 Impact Factor
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    ABSTRACT: Burn injuries, the most common and destructive forms of wounds, are generally accompanied with life-threatening infections, inflammation, reduced angiogenesis, inadequate extracellular matrix production, and lack of growth factor stimulation. In the current study, a new antimicrobial carbopol-based hydrogel formulated with boron and pluronic block copolymers was evaluated for its healing activity using in vitro cell culture techniques and an experimental burn model. Cell viability, gene expression, and wound healing assays showed that gel formulation increased wound healing potential. In vitro tube-like structure formation and histopathological examinations revealed that gel not only increased wound closure by fibroblastic cell activity, but also induced vascularization process. Moreover, gel formulation exerted remarkable antimicrobial effects against bacteria, yeast, and fungi. Migration, angiogenesis, and contraction-related protein expressions including collagen, α-smooth muscle actin, transforming growth factor-β1, vimentin, and vascular endothelial growth factor were considerably enhanced in gel-treated groups. Macrophage-specific antigen showed an oscillating expression at the burn wounds, indicating the role of initial macrophage migration to the wound site and reduced inflammation phase. This is the first study indicating that boron containing hydrogel is able to heal burn wounds effectively. The formulation promoted burn wound healing via complex mechanisms including stimulation of cell migration, growth factor expression, inflammatory response, and vascularization.
    Biological trace element research 04/2015; DOI:10.1007/s12011-015-0338-z · 1.61 Impact Factor
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    ABSTRACT: Testicular torsion is a urological emergency. Failure of timely intervention with this issue leads the testicles to go into necrosis, and if left untreated, can lead to the loss of the reproductive organs. The aim of this study was to examine the role of ALS in testicular torsion and detorsion injuries. Rats were divided into eight groups (n=12): SHAM, SHAM+ALS200, TOR, TOR/DET, TOR+ALS100, TOR+ALS200, TOR/DET+ALS100, and TOR/DET+ALS200. Drug administration has been carried out before 30 minutes from ischemia and reperfusion. Moreover, aliskiren administration has been carried out before 24 hours from the experiment protocol in all treatment groups. Ischemia and reperfusion was applied for 2 hours respectively. Testicular damage decreased SOD and GSH, and increased MDA in the testis tissues of rats, while aliskiren administration increased SOD and GSH, and decreased MDA in the testis tissues measured by using a biochemical autoanalyser. In addition, this Torsion/Detorsion damage caused a significant increase in inflammatory cytokine and agent levels IL-1β and iNOS examined by using real-time PCR, while aliskiren administration decreased these parameters. In the pathologic evaluation, the administration of a 200 mg/kg dose of aliskiren was found to protect the testis. RAAS inhibition with aliskiren caused an increase in serum renin levels and a decrease in serum angiotensin II levels. It appears that aliskiren protects the testis from I/R damage by regulating inflammation and oxidant-antioxidant balance via RAAS inhibition. Copyright © 2015 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.
    The Journal of urology 04/2015; DOI:10.1016/j.juro.2015.03.117 · 3.75 Impact Factor
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    ABSTRACT: The aim of this study was to examine the effects of carnitine on bone healing in ovariectomy (OVX) and inflammation (INF)-induced osteoporotic rats.The rats were randomly divided into nine groups (n=8): sham-operated (Group 1: SHAM), sham+magnesium silicate (Mg-silicate) (Group 2: SHAM+INF); ovariectomy (Group 3: OVX); ovariectomy+femoral fracture (Group 4: OVX+FRC); ovariectomy+femoral fracture+Mg-silicate (Group 5:OVX+FRC+INF); ovariectomy+femoral fracture+carnitine 50 mg/kg (Group 6: OVX+FRC+CAR50); ovariectomy+femoral fracture+carnitine 100 mg/kg (Group 7: OVX+FRC+CAR100); ovariectomy+femoral fracture+Mg-silicate+carnitine 50 mg/kg (Group 8: OVX+FRC+INF+CAR50); ovariectomy+femoral fracture+Mg-silicate+carnitine 100 mg/kg (Group 9: OVX+FRC+INF+CAR100). Eight weeks after OVX, which allowed for osteoporosis to develop, INF was induced with subcutaneous Mg-silicate. On day 80, all of the rats in Groups 4-9 underwent fracture operation on the right femur.Bone mineral density (BMD) showed statistically significant improvements in the treatment groups. The serum markers of bone turnover (osteocalcin and osteopontin) and pro-inflammatory cytokines (tumour necrosis factor α, interleukin 1β and interleukin 6) were decreased in the treatment group. The X-ray images showed significantly increased callus formation and fracture healing in the groups treated with carnitine.The present results show that in a rat model with osteoporosis induced by ovariectomy and Mg-silicate, treatment with carnitine improves the healing of femur fractures.This article is protected by copyright. All rights reserved.
    Basic & Clinical Pharmacology & Toxicology 01/2015; DOI:10.1111/bcpt.12384 · 2.29 Impact Factor
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    ABSTRACT: Contrast medium-induced nephropathy (CIN) remains as a problem with high incidence and mortality rates. The aim of this study is to examine the roles of infliximab (INF) in the glycerol (GLY) and CIN model in rats. The rats were separated into five groups (n = 8): Healthy, GLY, GLY + CM, GLY + CM + INF 5 mg/kg intraperitoneally (i.p.), and GLY + CM + INF 7 mg/kg (i.p.).
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    ABSTRACT: Abstract Purpose: To determine the protective effect of aliskiren on ischemia-reperfusion (I/R) injury in a rat renal (I/R) model. Methods: Rats were randomly divided into five groups: sham control group; sham control with aliskiren pretreatment; I/R group and I/R with two doses of aliskiren pretreatment. Rats were unilaterally nephrectomized and subjected to 45 min of renal pedicle occlusion followed by 24 h reperfusion. Aliskiren (50 and 100 mg/kg) was administered orally by gavage 24 and 1 h prior to ischemia. After 24 h reperfusion, kidney samples were taken for the determination of malondialdehyde (MDA) level, superoxide dismutase (SOD), glutathione (GSH) activity and histological evaluation. The level of serum creatinine (SCR) and blood urea nitrogen (BUN), renin and angiotensin II (AT-2) was measured in serum samples. Results: Kidneys from I/R groups showed significant increase in MDA level and significant decrease in GSH, and SOD activity. IL-1β, iNOS and NFkB gene expression significantly increased in the I/R groups in the rat kidney tissue. Aliskiren treatment showed a significant down-regulatory effect on IL-1β, iNOS and NFkB mRNA expression. Compared with the sham group, SCR and BUN, renin and AT-2 were significantly increased in the I/R rats, accompanied by histopathological damage to the kidney. Conclusion: Pretreatment with aliskiren ameliorated I/R-induced renal injury through decreasing nitric oxide and AT-2 levels and by the reduction of injury induced by I/R injury and ameliorated renal histopathological molecular and biochemical changes.
    Renal Failure 12/2014; 37(2):1-12. DOI:10.3109/0886022X.2014.991327 · 0.78 Impact Factor
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    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. DOI:10.1016/j.msec.2014.08.035 · 2.74 Impact Factor
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    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.
    International Journal of Neuroscience 10/2014; DOI:10.3109/00207454.2014.978976 · 1.53 Impact Factor
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    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.
    Archiv für Experimentelle Pathologie und Pharmakologie 07/2014; 387(10). DOI:10.1007/s00210-014-1014-0 · 2.36 Impact Factor
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    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; DOI:10.3109/08941939.2013.806615 · 1.19 Impact Factor
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    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; DOI:10.1016/j.ejphar.2013.05.010 · 2.68 Impact Factor
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    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.
    Immunobiology 04/2013; DOI:10.1016/j.imbio.2013.04.012 · 3.18 Impact Factor
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    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; 32(8). DOI:10.1177/0960327112472994 · 1.41 Impact Factor
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    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; 16(1). DOI:10.1016/j.intimp.2013.03.018 · 2.71 Impact Factor
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    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.
    Renal Failure 12/2012; DOI:10.3109/0886022X.2012.731999 · 0.78 Impact Factor
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    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.
    Basic & Clinical Pharmacology & Toxicology 09/2012; DOI:10.1111/bcpt.12004 · 2.29 Impact Factor
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    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; 43(6). DOI:10.1007/s10735-012-9441-z · 1.98 Impact Factor
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    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. DOI:10.5897/AJPP11.361 · 0.84 Impact Factor
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    ABSTRACT: Panax ginseng (PG) has been commonly used as medicinal herb for the treatment of various diseases in Eastern Asia for thousands of years. This study was designed to investigate the protective effect of PG against paracetamol-(N-acetyl-p-aminophenol; APAP)-induced liver damage in rats. Thirty-two albino Wistar rats were divided into four groups: Group C (control); Group APAP (gavaged orally with APAP (APAP, 2 g/kg, single dose); Group PG 100 mg/kg + APAP or 200 mg/kg + APAP (these two groups were treated by gavaging with PG (100 or 200 mg/kg) for 30 days following a single dose of APAP). APAP treatment alone induced hepatotoxicity, evidenced by significant increases in malondialdehyde (MDA) level and serum activities of alanine aminotransferase (ALT), aspartate aminotransferase (AST), and tumor necrosis factor-α (TNF-α). In addition, the level of GSH in the liver was significantly reduced, as were the activities of superoxide dismutase (SOD) and catalase (CAT). Liver histopathological examination showed that APAP administration induced centrilobular necrosis and infiltration of lymphocytes. However, these biochemical and histological changes were prevented by PG pretreatment. In conclusion, our results suggest that PG may be considered a protective medicinal herb against APAP-induced liver injury.
    African journal of pharmacy and pharmacology 06/2012; 6(36):2634-2642. DOI:10.5897/AJPP12.658 · 0.84 Impact Factor