Protective effect of leptin against ischemia-reperfusion injury in the rat small intestine

BACKGROUND: The small intestine is extremely sensitive to ischemia-reperfusion (I/R) injury and a range of microcirculatory disturbances which contribute to tissue damage. Previous studies have shown that leptin plays an important physiological role in the microvasculature. The aim of this study was to evaluate the protective effects of leptin in I/R – induced mucosal injury in the small intestine. METHODS: Forty rats were divided into 5 groups (n = 8). Group I was subjected to a sham operation. Following mesenteric ischemia in group II (control); physiologic saline 1 cm(3), in group III; leptin 100 μg/kg, and physiologic saline 1 cm(3), in group IV; N(G)-L-arginine methyl ester (L-NAME) 20 mg/kg, and physiologic saline 1 cm(3), in group V; leptin 100 μg/kg, L-NAME 20 mg/kg, and physiologic saline 1 cm(3 )were given intra-peritoneally. In these groups, an I/R procedure was performed by occlusion of the superior mesenteric artery for 45 min followed by 120 min reperfusion. After reperfusion, the small intestines were resected for malondialdehyde (MDA) and nitric oxide (NO) concentration and histopathologic properties. Mucosal lesions were scored between 0 and 5. Tissue MDA and NO concentration and histopathologic grades were compared statistically. RESULTS: Tissue MDA level significantly increased (P < 0.05), tissue NO level significantly decreased in group V animals, compared to group III animals respectively (P < 0.001). Histopathologically, intestinal injury significantly decreased in the leptin treated ischemic group. CONCLUSION: Leptin can be used safely in mesenteric occlusive diseases, since it induces NO formation and release in mesenteric vessels

Reproductive Effects of Nicotinamide on Testicular Function and Structure in Old Male Rats: Oxidative, Apoptotic, Hormonal, and Morphological Analyses.

Aging is a natural process in which morphological and functional abnormalities in living organisms increase irreversibly. Nicotinamide (NAM) acts both as a precursor of many metabolites and as a cofactor of many enzymes involved in cell energy metabolism, homeostasis of redox balance, and regulation of signaling pathways. In this study, we investigated the effects of NAM treatment on morphological and biochemical changes in testis of old rats. The rats were treated with 200, 400, and 800 mg/kg NAM doses as a gavage for 1 month. As a result, we determined the dose-dependent therapeutic effects of NAM on testicular tissues of aged rats. We found that NAM treatment decreased total oxidant status (TOS), caspase 3 (CASP3) and cytochrome c (CYC) levels and increased total antioxidant status (TAS), follicle-stimulating hormone (FSH), luteinizing hormone (LH), and testosterone levels (P<0.05). NAM treatment significantly reduced the age-related histopathological parameters such as cellular loss, necrotic tissue, interstitial edema, tubular damage, and vascular congestion in aged rat testicular tissue compared to the control group. Moreover, based on histomorphological analysis, we detected that NAM treatment resulted in a dose-dependent improvement in testicular tissue damage of old rats. Consequently, the results showed that the reproductive decline caused by aging could be ameliorated with NAM treatment.WOS:0006590244000032-s2.0-85107816162PubMed: 3410114

Ex Vivo Investigation of Bexarotene and Nicotinamide Function as a Protective Agent on Rat Synaptosomes Treated with A beta(1-42)

In this study, we were aimed to investigate the neuroprotective effects of bexarotene and nicotinamide in synaptosomes incubated with amyloid-beta (A beta). Our study consists of 2 parts, in vivo and in vitro. In the in vivo section, twenty-four Wistar albino male rats were divided into 4 groups (control, dimethyl sulfoxide (DMSO), nicotinamide and bexarotene) with six animals in each group. DMSO(1%), nicotinamide(100 mg/kg) and bexarotene(0.1 mg/kg) were administered intraperitoneally to animals in the experimental groups for seven days. In the in vitro part of our study, three different isolation methods were used to obtain the synaptosomes from the brain tissue. Total antioxidant capacity(TAS), total oxidant capacity(TOS), cleaved caspase 3(CASP3), cytochrome c(Cyt c), sirtuin 1(SIRT1), peroxisome proliferator-activated receptor gamma(PPAR gamma) and poly(ADP-ribose) polymerase-1(PARP-1) levels in the synaptosomes incubated with a concentration of 10 mu M A beta(1-42) were measured by enzyme-linked immunosorbent assay method. Biochemical analysis and histopathological examinations in serum and brain samples showed that DMSO, nicotinamide and bexarotene treatments did not cause any damage to the rat brain tissue. We found that in vitro A beta(1-42) administration decreased TAS, SIRT1 and PPAR gamma levels in synaptosomes while increasing TOS, CASP3, Cyt c, and PARP1 levels. Nicotinamide treatment suppressed oxidative stress and apoptosis by supporting antioxidant capacity and increased PPAR gamma through SIRT1 activation, causing PARP1 to decrease. On the other hand, bexarotene caused a moderate increase in SIRT1 levels with PPAR gamma activation. Consequently, we found that nicotinamide can be more effective than bexarotene in AD pathogenesis by regulating mitochondrial functions in synaptosomes.Eskisehir Osmangazi University Scientific Research CommissionEskisehir Osmangazi University [201811D21]This study was supported by Eskisehir Osmangazi University Scientific Research Commission with grant number 201811D21.WOS:0006070288000022-s2.0-85099087207PubMed: 3342809

Concanavalin A induces apoptosis in a dose-dependent manner by modulating thiol/disulfide homeostasis in C6 glioblastoma cells.

Glioma is the most common brain tumor. C6 rat glioblastoma cells provide thepossibility to the scientist to study brain cancer. Concanavalin A (Con A) has a lot ofantitumoral effects, especially over oxidative stress. In the present study, it wasaimed to decide the impacts of various doses of Con A on C6 glioblastoma cellsregarding cytotoxicity, thiol/disulfide homeostasis, apoptosis, and inflammation. Wedetected the cytotoxic activity of Con A (from 7.8 to 500 µg/ml) in C6 cells byutilizing 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyl tetrazolium bromide (MTT) anddetermined the toxic concentration of Con A. Once the optimal doses were found,the thiol–disulfide homeostasis, levels of total antioxidant and oxidant status (TASand TOS), malondialdehyde (MDA) and glutathione (GSH), pro‐inflammatory cytokines as tumor necrosis factor‐alpha (TNF‐α) and interleukin‐6 (IL‐6), apoptoticproteins as cytochrome c (CYCS), and caspase 3 (CASP3) were measured. Apoptoticand morphological changes in the C6 cells were examined with an inverted microscope and flow cytometry technique. Dose‐dependent Con A triggered oxidativedamage in the C6 cells, affecting the inflammatory pathway, so reducing proliferation with apoptotic proteins and morphological changes. But especially, Con A increased disulfide formation by disrupting the thiol/disulfide balance in C6 cells. Thisstudy revealed that Con A, known as carbohydrate‐binding protein, generatedoxidative damage, inflammation, and apoptosis in a dose‐dependent manner bymodulating thiol/disulfide homeostasis in C6 glioblastoma cells.</p

Effects of Curcumin and Boric Acid Against Neurodegenerative Damage Induced by Amyloid Beta (1-42)

Synaptosomes are used as an ex vivo model in the investigation of neuronal transmission and neurodegenerative processes. In this study, we aimed to determine the protective effects of boric acid (BA) and curcumin, which have antioxidant and anti-inflammatory properties, on A beta 1-42 induced neurodegenerative damage. Synaptosomes obtained from the rat cerebral cortex were divided into five groups: control, 10 mu M A beta 1-42, 10 mu M A beta 1-42 + 25 mM BA, 10 mu M A beta 1-42 + 10 mu M curcumin, and 10 mu M A beta 1-42 + 25 mM BA+10 mu M curcumin. Synaptosomes treated with A beta 1-42 caused a significant decline in synaptophysin levels and increase in malondialdehyde (MDA) levels, acetylcholinesterase (AChE) activities, DNA fragmentation values, and nitric oxide (NO) levels compared with the control group (P < 0.01). Synaptosomes treated with BA showed a significant reduction in MDA and NO levels against A beta 1-42 exposure (P < 0.01). In addition, curcumin treatment has been found to cause a significant reduction in AChE activities and MDA levels in synaptosomes (P < 0.05). Co-administration of BA and curcumin on synaptosomes exposed to A beta 1-42 resulted in a significant decrease in DNA fragmentation values, MDA levels, and AChE activities. Curcumin and BA + curcumin combination showed an enhancement in synaptophysin levels of A beta 1-42-induced synaptosomes (P < 0.01). The results showed that BA and curcumin had protective effects on rat brain synaptosomes against A beta 1-42 exposure. BA and curcumin treatment can have abilities to prevent the alterations of the cholinergic system and inhibit oxidative stress in the cerebral cortex synapses of A beta 1-42 exposed.WOS:0005925762000022-s2.0-85096556157PubMed: 3323749

Prenatal alcohol-induced neuroapoptosis in rat brain cerebral cortex: protective effect of folic acid and betaine

WOS: 000398041500006PubMed ID: 28062893Purpose Alcohol consumption in pregnancy may cause fetal alcohol syndrome (FAS) in the infant. This study aims to investigate prenatal alcohol exposure related neuroapoptosis on the cerebral cortex tissues of newborn rats and possible neuroprotective effects of betaine, folic acid, and combined therapy. Methods Pregnant rats were divided into five experimental groups: control, ethanol, ethanol + betaine, ethanol + folic acid, and ethanol + betaine + folic acid combined therapy groups. We measured cytochrome c release, caspase-3, calpain and cathepsin B and L. enzyme activities. In order to observe apoptotic cells in the early stages, TUNEL method was chosen together with histologic methods such as assessing the diameters of the apoptotic cells, their distribution in unit volume and volume proportion of cortical intact neuron nuclei. Results Calpain, caspase-3 activities, and cytochrome c levels were significantly increased in alcohol group while cathepsin B and L. activities were also found to be elevated albeit not statistically significant. These increases were significantly reversed by folic acid and betaine + folic acid treatments. While ethanol increased the number of apoptotic cells, this increase was prevented in ethanol + betaine and ethanol + betaine + folic acid groups. Morphometric examination showed that the mean diameter of apoptotic cells was increased with ethanol administration while this increase was reduced by betaine and betaine + folic acid treatments. Conclusion We observed that ethanol is capable of triggering apoptotic cell death in the newborn rat brains. Furthermore, folic acid, betaine, and combined therapy of these supplements may reduce neuroapoptosis related to prenatal alcohol consumption, and might be effective on preventing fetal alcohol syndrome in infants.TUBITAK [109S510]This work was supported by TUBITAK 109S510 project

Curcumin and LOXblock-1 ameliorate ischemia-reperfusion induced inflammation and acute kidney injury by suppressing the semaphorin-plexin pathway

Aims: Ischemia/reperfusion (I/R) is one of the most important causes of acute kidney injury (AKI), a clinical syndrome with kidney dysfunction and high mortality rates. New diagnostic biomarkers need to be defined to better illuminate the pathophysiology of AKI. For the first time, we aim to investigate the protective effects of Curcumin which is known for its antioxidant and anti-inflammatory properties and 12/15 lipoxygenase inhibitor LOXblock-1 on I/R induced AKI by modulating inflammatory processes, oxidative stress, apoptosis and semaphorin-plexin pathway. Main methods: The rats were divided into five groups, with eight animals per group: Sham, I/R, I/R + DMSO (1%, i.p.), I/R + Curcumin (100 mg/kg, i.p.), I/R + LOXblock-1 (2 mu g/kg, i.p.). Key findings: The renal function biomarkers (BUN, CREA and UA) in serum were significantly increased in the I/R group. The inflammatory (TNF-alpha, IL-6 and MCP-1), apoptotic (CYCS and CASP3) and oxidative stress parameters (MDA, MPO, TAS and TOS) measured by ELISA were significantly increased in the I/R group. In histopathological analysis, it was observed that I/R caused serious damage to kidney tissue. SEMA3A was found to increase both serum level and mRNA expression in I/R group. It was observed that curcumin and LOXblock-1 reduce inflammatory processes, oxidative stress and apoptosis via the semaphorin-plexin pathway by both measurements and histopathological analysis. Curcumin was proved more effective than LOXblock-1 with its antioxidant feature in I/R injury. Significance: The current study reveals the protective effects of Curcumin and LOXblock-1 on acute kidney injury by suppressing SEMA3A as a new biomarker.Commission of Scientific Research Projects of Eskisehir Osmangazi University, Eskisehir, Turkey [2019-2344, 2019-1915]This study was supported by the Commission of Scientific Research Projects of Eskisehir Osmangazi University, Eskisehir, Turkey with the grant numbers: 2019-2344 and 2019-1915.WOS:0005607654000092-s2.0-85087120412PubMed: 3260381

The neuroprotective effect of acute moderate alcohol consumption on caspase-3 mediated neuroapoptosis in traumatic brain injury: The role of lysosomal cathepsin L and nitric oxide

Our aim in this study was to investigate the effect of moderate acute alcohol administration on cysteine protease mediated neuronal apoptosis and nitric oxide production in the traumatic brain injury. A total of 29 adult Sprague-Dawley male rats weighing 250-300 g were used. The rats were allocated into four groups. The first group was the control (sham-operated) group in which only a craniotomy was performed, the others were alcohol, trauma and trauma + alcohol groups. Caspase-3 enzyme activity in the trauma group increased significantly in comparison with the control group. The alcohol given group showed a decreased caspase-3 enzyme activity compared to the trauma group. The level of caspase-3 enzyme activity in the alcohol + trauma group decreased in comparison to the trauma group. SF/EEL ratio of cathepsin-L enzyme activity in the trauma group was significantly higher than in the control group. Our results indicate that moderate alcohol consumption may have protective effects on apoptotic cell death after traumatic brain injury. Protective effects of moderate ethanol consumption might be related to inhibition of lysosomal protease release and nitric oxide production. Published by Elsevier B.V

Comparative effects of metformin and Cistus laurifolius L. extract in streptozotocin-induced diabetic rat model: oxidative, inflammatory, apoptotic, and histopathological analyzes.

AbstractInterest in phytochemical therapy methods in the treatment of diabetes is increasing day by day. Although the antidiabetic andantioxidant effects of Cistus laurifolius L. (CL) have been mentioned, the systemic effects remain unknown. The present study aimsat evaluating the antidiabetic effects of the CL aqueous extract via metformin on streptozotocin (STZ)-induced diabetic rats. Forty maleWistar albino rats were divided into five groups of eight animals each: control, diabetic group (55mg/kg STZ), STZ+125mg/kg CL,STZ+250mg/kg CL, and STZ+100mg/kg metformin. The effects of CL and metformin on oxidative, apoptotic, and inflammatorypathways were comparatively investigated. In addition, nuclear factor-κB(NFκB), tumor necrosis factor-alpha (TNF-α), and interleukin(IL)-1β expressions analysis were carried out. CL treatment resulted in a significant improvement in blood glucose levels, lipid profile,pancreatic markers, and liver and kidney function tests. A 250mg/kg CL treatment decreased by 67.9%, 31.6%, 66.8%, 28.3%, and31.4% in the total oxidant capacity, NFκB, TNF-α, IL-1β, caspase3, and cytochrome c levels, respectively, compared to the diabeticgroup. Additionally, CL treatments showed a dose-dependent reduction in NFκB, TNF-α, and IL-1β expression levels. A 250mg/kgCL treatment exhibited a greater increase (by 9.6%) in total antioxidant capacity than metformin. CL treatment provided histologicallymore improvement in the brain, heart, pancreas, spleen, liver, kidney, and testicular tissues compared to the metformin group. Ourresults suggest that the single treatment of CL aqueous extract at the low doses may have stronger short-term anti-diabetic effects thanmetformin. Therefore, further studies are needed regarding the long-term hypoglycemic effect or treatment of CL aqueous extract.Keywords Diabetes . Cistus laurifolius L. .Metformin . Oxidative stress . Apoptosis . Inflammation . Histopathology</p

Development of Gruenhagen's space at tip of a villus in group III rats (Grade II) (HE, ×100)

<p><b>Copyright information:</b></p><p>Taken from "Protective effect of leptin against ischemia-reperfusion injury in the rat small intestine"</p><p>BMC Gastroenterology 2005;5():37-37.</p><p>Published online 21 Nov 2005</p><p>PMCID:PMC1334207.</p><p>Copyright © 2005 Hacioglu et al; licensee BioMed Central Ltd.</p