Costunolide prevents renal ischemia-reperfusion injury in rats by reducing autophagy, apoptosis, inflammation, and DNA damage.

Objectives: Renal ischemia-reperfusion (I/R) is a vital health condition leading to acute kidney injury. Costunolide (COST) is an actively used molecule clinically for its anti-inflammatory, antioxidant, and immunomodulatory properties. In the present study, we searched for the possible protective effects of COST against renal ischemia/reperfusion (I/R) injury in rats. Materials and Methods: We established a renal I/R rat model. We divided forty rats into four groups: group I (sham), group II (I/R), group III (I/R+COST 5 mg/kg), and group IV (I/R+COST 10 mg/kg). We collected blood, kidney, and lung samples for analysis. Results: COST administration performed anti-oxidant and anti-inflammatory activity by reducing oxidant parameters and proinflammatory cytokine levels. COST alleviated DNA damage through declining 8-hydroxydeoxyguanosine (8-OHdG) levels. In addition, COST diminished tubular damage and inflammation by reducing kidney injury molecule-1 (KIM-1) production. COST administration also ameliorated apoptosis and autophagy by decreasing caspase-3 and microtubule-associated protein light chain 3B (MAPLC3, LC3B) expression. Conclusion: COST demonstrated protective effects against renal I/R-induced injury.

Effects of Polygonum cognatum Meissn. extract on indomethacin induced gastric damage in rats.

We investigated the anti-ulcer activity of ethanol extracts of Polygonum cognatum on indomethacin induced gastric damage in rats. We evaluated the number of ulcer areas, oxidant and antioxidant parameters as well as histopathologic features in rat stomach. We measured the total antioxidant status of P. cognatum in concentrations from 1.56-100 mg/ml. P. cognatum extract inhibited indomethacin induced ulcer formation with an effect similar to a 20 mg/kg dose of the standard anti-ulcer drug, esomeprazole. All doses of P. cognatum extract exhibited positive effects on oxidative stress markers and histopathological features in the stomach tissue of rats. We suggest that the antioxidant activity of P. cognatum extract may be responsible for its gastroprotective effect and that P. cognatum extract may be a useful gastroprotective agent.

Reproductive Effects of S. boulardii on Sub-Chronic Acetamiprid and Imidacloprid Toxicity in Male Rats.

The potential health-promoting effects of probiotics against intoxication by pesticides is a topic of increasing commercial interest with limited scientific evidence. In this study, we aimed to investigate the positive effects of probiotic Saccharomyces boulardii on the male reproductive system under low dose neonicotinoid pesticide exposure conditions. We observed that acetamiprid and imidacloprid caused a degeneration and necrosis of the spermatocytes in the tubular wall, a severe edema of the intertubular region and a hyperemia. This was concomittant to increased levels of 8-hydroxy-2'-deoxyguanosine reflecting oxidative stress, and an increase in caspase 3 expression, reflecting apoptosis. According to our results, Saccharomyces boulardii supplementation mitigates these toxic effects. Further in vivo and clinical studies are needed to clarify the molecular mechanisms of protection. Altogether, our study reinforces the burden of evidence from emerging studies linking the composition of the gut microbiome to the function of the reproductive system.

Effects of simultaneous versus post exposure epigallocatechin-3-gallate treatment on aluminum induced neurotoxicity in rat hippocampus: A multi-approach study.

Chronic aluminium(Al) exposure can affect the antioxidant and glutaminergic systems through N-methyl-D-aspartate receptors (NMDAR). This study was aimed to investigate the neurotoxic effect of Al through different mechanisms in rat hippocampus and to evaluate the protective role of epigallocatechin gallate (EGCG), a well-known antioxidant, with simultaneous administration of Al,as well as post-treatment after Al exposure.For this purpose, aluminum chloride(AlCl3) was administered simultaneously with two different EGCG doses for 8 weeks as the first part of the study.In the second part of the study, after 4 weeks of AlCl3 pre-administration, two different EGCG doses were also administered during four additional weeks as post-treatment.Al administration led to oxidative stress and increased acetylcholinesterase levels.NMDAR subunit mRNA expressions were down-regulated by Al, which was apparent in NMDAR1/2B subunits.Simultaneous EGCG treatment has shown a better neuroprotective effect in terms of these mechanisms and represents novel approach for the prevention of neurodegenerative diseases likely to be induced by Al.

Protective Effects of Idebenone against Sepsis Induced Acute Lung Damage.

BACKGROUND/AIMS: Sepsis is an uncontrolled systemic infection, withcomplex pathophysiology that may result in acute lung organ damage and cause multiple organ failure. Although much research has been conducted to illuminate sepsis's complex pathophysiology, sepsis treatment protocols are limited, and sepsis remains an important cause of mortality andmorbidity in intensive care units.Various studies have shown that idebenone (IDE) possesses strong antioxidant properties, which inhibit lipid peroxidation and protect cells from oxidative damage. The present study aimed to evaluate the protective effects of IDE against lung injury in a cecal ligation and puncture (CLP)-induced sepsis rat model. METHODS: Male albino Wistar rats were used. The animals were divided into a healthy control (no treatment), CLP, IDE control (200 mg/kg), and CLP + IDE subgroups (50 mg/kg, 100 mg/kg, and 200 mg/kg), with nine rats in each group.IDE was administered 1 h after CLP induction.To evaluate the protective effects of IDE, lung tissues were collected 16 h after sepsis for biochemical, immunohistochemical staining, and histopathological examination. RESULTS: IDE significantly ameliorated sepsis-induced disturbances in oxidative stress-related factors, with its effects increasing in accordance with the dose.IDE also abolished histopathological changes in lung tissues associated with CLP.Furthermore, interleukin 1 beta (IL-1ß)and tumor necrosis factor-alpha (TNF-α) immunopositivity markedly decreased in the septic rats following IDE treatment. CONCLUSIONS: IDE largely mitigated the inflammatory response in sepsis-induced lung injury by decreasing free radicals and preventing lipid peroxidation. The results suggest that IDE may represent a potential novel therapeutic drug for sepsis treatment.

5-HT7 receptors as a new target for prostate cancer physiopathology and treatment: an experimental study on PC-3 cells and FFPE tissues.

Prostate cancer (PCa) is one of the most common types of cancer seen among men worldwide. Previous studies have demonstrated that serotonin regulates cell proliferation, migration, and invasion in vitro; the presence of 5-HT receptors in cancer cells; and the role of serotonin in tumor development. The most recently discovered of these receptors is 5-HT7 but also least characterized receptors of serotonin. The aim of this study is to investigate the existence and possible role of 5-HT7 receptors in healthy and cancerous prostate tissues and also investigate effects of receptor agonists and antagonists on PC-3 cells to evaluate potential therapeutic effects. PC-3 cells were cultured and effects of 5-HT7 receptor agonist (LP-44) and antagonist (SB-269970) were evaluated on these cells. After proliferation analyses, relative expression of apoptotic markers and 5-HT7 receptor mRNA expression levels were determined through real-time PCR. Annexin V-FITC/PI double staining and Hoechst 33258 staining assay methods were applied to determine apoptosis. Additional PCR studies were performed on healthy and cancerous prostate tissue to see existence of receptors in human samples. The viability of PC-3 cells was decreased by SB-269970 after 48 and 72 h of incubation. However, LP-44 increased PC-3 cell proliferation at all time points. In 10-6 M SB-269970 treated PC-3 cells, there was significant increase in the expression of CAS-3 (4-fold), CAS-9 (2.5-fold), BAX (1.9-fold), and Tp-53 (4.8-fold) gene mRNA levels when compared to non-treated control group. Conversely, there was a significant decrease in NF-κB (2.9-fold) and 5-HT7 receptor (3.6-fold) mRNA expression in cells treated with SB-269970 when compared to control. SB-269970 that antagonized 5-HT7 receptors also induced apoptosis in Annexin V-FITC/PI double staining assay and Hoechst 33258 staining assays when compared with other groups. In human samples, 5-HT7 receptor mRNA expression was approximately 200-fold higher than that of heathy ones. In this study, for the first time, the 5-HT7 receptor antagonist SB-269970 has been shown to inhibit proliferation in PC-3 cells and to be associated with an apoptosis-inducing effect. These results suggest blocking 5-HT7 receptors can be a novel therapeutic target for the treatment of prostate cancer.

Effect of surfactant alkyl chain length on lyotropic uniaxial to biaxial cholesteric phase transitions.

Some ionic surfactant-based lyotropic mixtures, exhibiting cholesteric phases, were prepared to investigate the effect of the surfactant alkyl chain length on a) uniaxial-to-biaxial phase transitions and b) stabilization of different cholesteric phases. Potassium alkanoates, KCx, (potassium undecanoate, KC11, potassium dodecanoate, KC12, and potassium tridecanoate, KC13) were chosen as the surfactant molecules. The lyotropic mixtures, which were composed of KCx/potassium sulfate (K2SO4)/decanol (DeOH)/water/brucine, where brucine is a chiral dopant molecule, were studied. Partial phase diagrams were constructed to show how the surfactant alkyl chain affects the phase topologies in the phase diagrams. It was observed that the presence of a longer surfactant alkyl chain in the mixture favors the stabilization of the larger discotic cholesteric, ChD, and cholesteric biaxial, ChB, phase domains. The phase transitions from the uniaxial cholesteric to biaxial cholesteric phase were shifted to lower temperatures.

The effects of Beeswax, Olive oil and Butter impregnated bandage on burn wound healing.

BACKGROUND: Beeswax, Olive oil and Butter (BOB) are nutritive products that could support wound healing by adsorption to bandage. This study demonstrated the therapeutic effects of BOB on second degree burn. METHODS: Second degree burn model was created in rats. Experimental groups were assigned to Healthy, Burn, Silver Sulfadiazine (SS) and BOB. The effects of BOB were evaluated on skin regeneration, vesicles and bullae and fibroblast activity by histopathological analyses and wound contraction percent were determined. Transforming Growth Factor-Beta1 (TGF-ß1) and Vascular Endothelial Growth Factor-alpha (VEGF-α) mRNA expressions were analyzed with Real Time-Polymerase Chain Reaction. All parameters analyzed at 3rd, 7th, 14th days. RESULTS: The BOB treatment increased TGF-ß1 and VEGF-α expressions compared to Burn group. The histopathological analyses showed that epidermis and dermis layers injured due to burn. BOB treatment augmented the regeneration of these layers and increased fibroblast activity and keratinization which are play important role on the new blood vessels production. Also with the BOB treatment we showed wound contraction levels were higher than Burn and SS treatment. CONCLUSION: This study demonstrated that beeswax-olive oil-butter mixture impregnated bandage treatment in a second-degree burn rat model improved burn wound healing and encouraged skin renewal via modulating tissue TGF-ß1 and VEGF-α.

Effect of head-group size of some tetradecylalkylammonium bromide surfactants on obtaining the lyotropic biaxial nematic phase.

Lyotropic quaternary mixtures of some tetradecylalkylammonium bromide surfactants were prepared to examine the effect of the size of the surfactant head group on the stabilization of different lyotropic nematic phases. The lyotropic mixtures were prepared by the addition of the tetradecylalkylammonium bromides (TTAABr) in the mixture of NaBr/decanol (DeOH)/water. The uniaxial to biaxial nematic phase transitions were determined via laser conoscopy. Some micellization parameters such as critical micelle concentration, degree of counterion binding and micellization Gibbs energy were evaluated from the electrical conductivity measurements of diluted binary surfactants/water solutions. The results indicate that the head-group size of the surfactant molecules influences the amphiphilic molecular aggregate topology. Moreover, the effective area per surfactant head group is a key parameter on stabilizing the lyotropic biaxial nematic phase.

Urotensin receptors as a new target for CLP induced septic lung injury in mice.

Sepsis is a life-threatening organ dysfunction condition response resulting in acute lung injury. Urotensin II (UII), an endogenous vasoactive peptide, is widely distributed in pulmonary, cardiovascular, central nervous, renal and metabolic systems, and especially in inflammatory regions. This study aimed to investigate whether urotensin II (UII) and UII receptor (UTR) antagonists play a role in the inflammatory response to sepsis-induced lung damage and they are possible therapeutic targets. In the study, 78 male Balb-c mice were used. A cecal ligation and puncture (CLP)-induced polymicrobial sepsis model was applied, and the effects of human urotensin II (agonist) and urantide and palosuran (antagonists) were investigated on lung tissues. Glutathione and malondialdehyde levels and SOD activity of lung tissues were investigated in addition to TNF-α, IL-1ß, IL-6, NF-κB, and UTR mRNA levels. Also, lung sections were histopathologically evaluated. Urantide and palosuran, UII receptor antagonists, decreased proinflammatory cytokines such as TNF-α, IL-1ß, IL-6, NF-κB, and also decreased oxidative stress parameters in lung tissue, which are markers of damage. UTR mRNA expression was increased in septic lungs, and both antagonists significantly decreased the elevated receptor level. Also, histopathological examination showed beneficial effects of both agonists on lung tissue. The results of this study help to understand the inflammatory and therapeutic contribution of the UII/UTR system on sepsis-induced lung damage. We can suggest that UTR receptor antagonists may be evaluated as a potential drug which reduces sepsis-induced lung damage in the future.

Effects of Aliskiren, an RAAS inhibitor, on a carrageenan-induced pleurisy model of rats.

Our aim is to investigate the potentially preventive effects of Aliskiren in a carrageenan-induced lung pleurisy model and to compare the standard anti-inflammatory agents, indomethacin and dexamethasone. The pleurisy model was induced through the injection of carrageenan (0.2 ml-%2) into the pleural cavity. After the experiment, serum and lung tissues were collected and biochemical, molecular and pathological examinations were performed. In our study, pleural inflammation decreased superoxide dismutase activity and the glutathione level and increased the malondialdehyde level in the lung of rats, while Aliskiren increased the superoxide dismutase activity and glutathione level and decreased the malondialdehyde level. In addition, carrageenan-induced pleurisy caused a significant increase in pro-inflammatory cytokines mRNA expressions (TNF-α, IL-1ß, and NF-KB), while Aliskiren administration decreased their expressions as well as the standard treatments, indomethacin and dexamethasone, did. Aliskiren administration at the 200 mg/kg dose protected the lungs in the pathological evaluation, especially against inflammatory cell infiltration and edematous lesions. It appears that Aliskiren protects the lung from carrageenan-induced pleurisy damage by regulating inflammation and antioxidant-oxidant balance via Renin Angiotensin Aldosterone System inhibition.

Serum nesfatin-1 levels: a potential new biomarker in patients with subarachnoid hemorrhage.

BACKGROUND: Acute subarachnoid hemorrhage (SAH) is a neurological emergency with significant potential for long-term morbidity and mortality. Nesfatin-1 is a polypeptide which is found in various regions of the brain that play role in the feeding and metabolic regulation. OBJECTIVE: So this study aimed to investigate if nesfatin-1 levels in patients with SAH, could be used as a marker for the severity and prognosis. METHOD: Forty-eight consecutive patients (except those excluded) admitted to the emergency service of our hospital and hospitalized at our clinic with the diagnosis of aneurysmal SAH between 2011 and 2013 were included in the study and followed up for six months for outcome. The control group consisted of 48 healthy individuals of similar age and gender. RESULTS: During the 6-month follow-up, 7 of 48 patients died and 16 (33.3%) patients had poor Glasgow Outcome Score (GOS) scores. In the study group, the mean nesfatin-1 level was significantly higher than the control group (7.36 ± 2.5 pg/ml and 4.29 ± 2.02 pg/ml, respectively; p < 0.01). The mean nesfatin-1 level was 11.58 ± 0.87 pg/ml in the non-survival group and 6.64 ± 1.89 pg/ml in the survival group. Furthermore, it was 10.22 ± 1.42 pg/ml in patients with poor outcome in terms of GOS and 5.93 ± 1.46 pg/ml in those with good outcome. The nesfatin-1 levels significantly increased with worsening of GOS, the World Federation of Neurological Surgeons grading system, and Fisher scores and increasing plasma C-reactive protein levels (p < 0.01 for all). CONCLUSION: The present study is the first that shows the mortality/poor outcome of the SAH with assessing serum nesfatin-1 levels. So levels of nesfatin-1 might be useful in SAH management.

The effects of apomorphine on paracetamol-induced hepatotoxicity in rats.

It is becoming progressively more understandable that overdose of paracetamol in both humans and animals causes severe hepatotoxicity. Apomorphine is known as a neuroprotective agent. Due to the protective effect,  apomorphine had been tested in experimental studies on different models. Findings obtained through series of expriments suggested that apomorphine may also be useful in liver toxicity. The aim of this study is to investigate the relationship among the hepatoprotective mechanism of apomorphine and to determine the possible role of apomorphine on paracetamol-induced hepatotoxicity in rats. 30 Sprague Dawley rats (adult male) were distributed into 5 groups. Group 1 was the control group and did not receive any medication. Group 2 received only paracetamol 2 g/kg by intragastric gavage to induce hepatotoxicity. Groups 3 and 4 were given apomorphine 1 mg/kg and 2 mg/kg by intraperitoneal injection, respectively. Groups 3 and 4 were given 2g/kg  of Paracetamol. In Group 5, rats were treated with 2 mg/kg of apomorphine. Drug-treated rats were given food for the next 24 h until they were sacrified. Moreover, we also performed AST, ALT measurements in serum, MDA and SOD levels in liver tissues and histopathological analysis of the liver in all groups. Apomorphine had positive effects on both liver enzymes, oxidative stress markers and histopathological results in paracetamol-induced hepatotoxicity. Additionally, apomorphine at 2 mg/kg dose was significantly more protective as compared to 1 mg/kg as evidenced by the histopathological examination results. It was thought that apomorphine was found hepatoprotective on paracetamol-induced hepatotoxicity, especially at higher doses such as 2 mg/kg.

Role of kosmotrope-chaotrope interactions at micelle surfaces on the stabilization of lyotropic nematic phases.

Three lyotropic quaternary systems of ionic surfactants were prepared to investigate the role of kosmotrope-chaotrope interactions at the micelle surfaces on stabilizing the different nematic phases. The ionic surfactants were potassium laurate (KL), sodium dodecylsulfate (SDS) and tetradecyltrimethylammonium bromide (TDTMABr), where KL is a kosmotrope surfactant, and others are chaotrope. The first system consisted of KL/decanol (DeOH)/water/alkali sulfate and the second of SDS/DeOH/water/alkali sulfate. The third system was prepared by adding sodium salts of chaotropic or kosmotropic anions to the primary mixture of TDTMABr/DeOH/water, separately. The characteristic textures of discotic nematic (N D), biaxial nematic (N B) and calamitic nematic (N C) phases were identified under polarizing light microscope. Laser conoscopy was employed to determine the uniaxial-to-biaxial phase transitions. The kosmotrope-kosmotrope or chaotrope-chaotrope interactions between the head groups of the surfactants and the ions of the electrolytes led to the stabilization of the N D phase. On the other hand, kosmotrope-chaotrope interactions stabilize the N B and/or N C phases.

The Effects of Argan Oil in Second-degree Burn Wound Healing in Rats.

Argan oil, produced from the kernels of the argan tree (Argania spinosa), has been shown to have antioxidant properties. To examine the effect of argan oil in second-degree burn wound healing, an in vivo experiment was conducted among 30 adult male Wistar rats divided into 5 equal groups: a sham group, a control group (burned but no topical agent), a group in which argan oil was applied once a day, a group in which argan oil was applied twice a day, and a group treated with 1% silver sulfadiazine once a day. Second-degree burns were created by scalding hot water (85˚ C for 15 seconds). Treatment began 24 hours after the burn injury; in the argan oil groups, 1 mL of argan oil was administered via syringe to the wound. The rate of wound healing was quantified by wound measurements on days 1, 7, and 14 after burn injury. Tissues were analyzed for molecular and histologic changes in TGF-ß expression and fibroblast activity. Percent contraction of burned skin tissue was determined using the stereo investigator program, which calculated the burn field to the millimeter. Means (SD) were calculated and compared using Duncan's multiple comparison test. The group receiving argan oil twice daily showed significantly increased mRNA levels of TGF-ß1 from 39.66- to 58.70-fold compared to the burn control group on day 14 (P less than 0.05). Both argan oil-treated groups showed significantly increased contraction compared to the burn control group at all 3 timepoints; the group receiving argan oil twice daily had a greater contraction rate (31% on day 7, 76% on day 14) than the silver sulfadiazine group (22% on day 7, 69% on day 14), (P less than 0.05). Histopathological assessments on days 3, 7, and 14 showed greater healing/contraction in both argan oil and silver sulfadiazine groups compared to the control group. These results suggest argan oil is effective in healing experimentally created second-degree burns in rats. Prospective, randomized, controlled clinical studies are needed to evaluate the safety, efficacy, and effectiveness of this treatment modality for patients with second-degree burn wounds.

The Role of Urotensin Receptors in the Paracetamol-Induced Hepatotoxicity Model in Mice: Ameliorative Potential of Urotensin II Antagonist.

We aimed to evaluate the possible protective effect of a UTR antagonist and to determine the effect of the antagonist on ALT and AST levels in serum, the mRNA expression level of UTR, tumour necrosis factor-alpha (TNF-α) and IL-1ß and SOD activity, GSH and MDA levels in liver tissues, which are important mediators or markers for the hepatotoxicity animal model in mice. Animals fasted overnight and were divided into seven equal groups (n = 12). The first group was the healthy group (administered 0.1% DMSO intraperitoneally). Group 2 received only paracetamol (PARA) (administered orally at a dosage of 300 mg/kg). Groups 3 and 4 were treated with only AGO (AC7954, UTR agonist) 15 and 30 mg/kg intraperitoneally, respectively. Groups 5 and 6 were treated with only ANTA (SB657510, UTR antagonist) 30 and 60 mg/kg intraperitoneally, respectively. Group 7 was treated with AGO 30 mg/kg and ANTA 60 mg/kg intraperitoneally. One hour after the pre-treatment drugs were administered, groups 3 through 7 were given PARA. After the experimental period, the mice were killed 6 and 24 hr after PARA was administered. Antagonist administration significantly decreased the ALT and AST levels, while agonist administration did not. In addition, SOD activity and GSH levels increased, and the MDA level decreased with the pre-treatment of two antagonist doses. The increased UTR gene expression through PARA was significantly lower in both doses of the antagonist groups at 24 hr when compared with the agonist and PARA groups. This study showed that UTR antagonists have hepatoprotective and anti-inflammatory effects on high-dose PARA-induced hepatotoxicity in mice.

The Effects of RAAS Inhibition in Rate Limiting Step by Aliskiren on Testicular Torsion Injury in Rats.

PURPOSE: Testicular torsion is a urological emergency. Failure of timely intervention for this issue leads the testicles to go into necrosis. If left untreated, it can lead to loss of the reproductive organs. The aim of this study was to examine the role of aliskiren in testicular torsion and detorsion injuries. MATERIALS AND METHODS: Rats were divided into 8 groups of 12 each, including no torsion-detorsion, no torsion-detorsion plus 200 mg/kg aliskiren orally, torsion, torsion-detorsion, torsion plus 100 mg/kg aliskiren orally, torsion plus 200 mg/kg aliskiren orally, torsion-detorsion plus 100 mg/kg aliskiren orally and torsion-detorsion plus 200 mg/kg aliskiren orally. Aliskiren was administered 30 minutes before ischemia and reperfusion, and also 24 hours before the experimental protocol in all treatment groups. Ischemia and reperfusion were each applied for 2 hours. RESULTS: Testicular damage decreased superoxide dismutase and glutathione, and increased malondialdehyde in the testis tissues of rats. Aliskiren administration increased superoxide dismutase and glutathione, and decreased malondialdehyde in the testis tissues. Values were measured by a biochemical autoanalyzer. In addition, this torsion-detorsion damage caused a significant increase in levels of the inflammatory cytokine and agents interleukin-1ß and inducible nitric oxide synthase, as examined by real-time polymerase chain reaction. Aliskiren administration decreased these parameters. On pathological evaluation administration of a 200 mg/kg dose of aliskiren was found to protect the testis. Renin-angiotensin-aldosterone system inhibition by aliskiren caused an increase in serum renin levels and a decrease in serum angiotensin II levels. CONCLUSIONS: It appears that aliskiren protects the testis from ischemia-reperfusion damage by regulating inflammation and the oxidant-antioxidant balance via renin-angiotensin-aldosterone system inhibition.

Tnf-α inhibition by infliximab as a new target for the prevention of glycerol-contrast-induced nephropathy.

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 5mg/kg intraperitoneally (i.p.), and GLY+CM+INF 7 mg/kg (i.p.). Antioxidant levels in the therapy groups were observed to be quite similar to those in the healthy group. In this study, while the kidney TNF-α, IL-1ß, TGF-1ß and Caspase 3 gene expressions' levels increased in the nephrotoxic groups, these levels were found to have decreased in the treatment groups. Moreover, histopathologic examination showed that hyaline, haemorrhagic casts and necrosis were increased in nephrotoxicity group, whereas they decreased in the therapy group. Furthermore, TNF-α and NF-κB expression were decreased with infliximab administrated groups similar to control group. In conclusion, we suggest that infliximab have protective roles on CIN.

Does bosentan protect diabetic brain alterations in rats? The role of endothelin-1 in the diabetic brain.

Diabetes mellitus (DM) is a major problem all over the world, affecting more people in recent years. Individuals with diabetes are more prone to disease than non-diabetics, especially vascular complications. The aim of this study was to examine the roles of the endothelin (ET)-1 in brain damage formed in a streptozocin (STZ)-induced diabetes model, and the effect of bosentan, which is the non-specific ET1 receptor blocker in the prevention of the diabetes-induced brain damage. To examine the effects of bosentan (50 mg/kg and 100 mg/kg) in this study, the rats were given the drug for 3 months. The rats were divided into four groups: the sham group (n = 10), the diabetic control group (n = 10), the group of diabetic rats given bosentan 50 mg/kg (n = 10) and the group of diabetic rats given bosentan 100 mg/kg (n = 10). Diabetes was induced in the rats by STZ (60 mg/kg i.p.). On day 91, all rats were killed. Brain tissues of the rats were measured by molecular, biochemical and histopathological methods. Antioxidant levels in the therapy groups were observed as quite near to the values in the healthy group. In this study, while the brain eNOS levels in the diabetic groups decreased, the ET1 and iNOS levels were found to be increased. However, in the diabetes group, hippocampus and cerebellum, pericellular oedema and a number of neuronal cytoretraction were increased in neuropiles, whereas these results were decreased in the therapy group. Based on all of these results, ET1 will not be ignored in diabetes-induced cerebral complications.

The double-edged sword: effects of pregabalin on experimentally induced sciatic nerve transection and crush injury in rats.

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: 1st group: healthy; 2nd group: axonotmesis control; 3rd group: anastomosis control; 4th group: axonotmesis+30 mg/kg of pregabalin; 5th group: axonotmesis+60 mg/kg of pregabalin; 6th group: anastomosis+30 mg/kg of pregabalin; 7th 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-ß 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-ß1.