Dose-dependent protective effects of Lactobacillus rhamnosus GG against stress-induced ulcer.

BACKGROUND: Stress-related diseases are on the rise and stress is one of the common factors that lead to ulcer. Stress-induced mucosal bleeding is a serious complication observed in many critically ill patients. Due to the harmful side effects of proton pump inhibitors, natural and active alternative treatment methods for peptic ulcer treatment that are safe in terms of side effects are an urgent need for human health. We aimed to investigate the dose-dependent protective effects of Lactobacillus rhamnosus GG (LGG) against stress ulcers induced by cold restraint stress in rats. This study was performed in a total of 42 rats, in control group (C), stress group (S), pantoprazol (20 mg kg-1 day-1) group (P), LGG (3 × 108 cfu mL-1 day-1) + stress group (M1), LGG (15 × 108 mL-1 day-1) + stress group (M5) and LGG (30 × 108 mL-1 day-1) + stress group (M10) (each n = 7). Ulceration areas (mm2) were determined quantitatively with ImageJ software. Glucocorticoid, catalase (CAT), superoxide dismutase (SOD) and glutathione peroxidase (GPx) levels were determined by ELISA and malondialdehyde levels were determined by spectrophotometric measurement. Histopathological examinations were performed in gastric tissue. RESULTS: Therapeutic dose of LGG increased CAT, SOD and GPx levels; prevented excessive activation of the hypothalamic-pituitary-adrenal axis; reduced ulceration and bleeding in the gastric mucosal layer; and provided stabilization of mast cells. CONCLUSIONS: We can suggest that LGG may be beneficial for reducing the negative effects of stress on the body, for protecting against ulcer disease and for reducing or preventing the risk of stress-induced gastrointestinal bleeding in patients staying in intensive care units. © 2024 The Author(s). Journal of The Science of Food and Agriculture published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.

Dose-related effects of ciproxifan on brain tissue in rats with cerebral ischemia-reperfusion.

PURPOSE: Cerebral ischemia is the result of decreased or interrupted blood flow to the brain. It is the third leading cause of death after cardiovascular disease and cancer. Cerebral ischemia is reversible or irreversible in neurons in the affected area, and subsequent free radical damage can be exacerbated if reperfusion occurs. Ciproxifan is used to study the involvement of histaminergic neurons in different phases such as wakefulness and cognition. We wanted to find out whether ciproxifan has a protective effect on the brain of rats with cerebral ischemia-reperfusion injury. MATERIALS AND METHODS: A total of 64 adult rats (32 male and 32 female) were used for the experiment. Eight cages were formed with randomly selected rats. No substance was administered to the rats in Group 1 and no surgical procedure was performed. The cerebral ischemia-reperfusion model (clamping of the left common carotid artery for 15 min followed by reperfusion for 24 h) was applied to rats in Group 2, Group 3, and Group 4 after 7 days/single dose of saline and ciproxifan (10 mg/kg, 30 mg/kg). After that, the activitymeter, forced swim test (FST), and Morris water maze (MWM) were performed on all animals. RESULTS: Rats treated with ciproxifan exhibit neurons and glial cells with histologic structures similar to those of the control group, and interestingly, these differences became more pronounced with increasing dose. Rats administered ciproxifan improved motor coordination, decreased total distance behavior, and improved learning ability. However, when the groups were compared by sex, no significant difference was found in the parameters. CONCLUSION: Thus, we could conclude that ciproxifan has a protective effect on the brain to a certain extent, regardless of the dose.

Cerebral ischemia is one of the leading causes of death.Cerebral ischemia is a common mechanism of acute brain injury that results from impaired blood flow to the brain.Ciproxifan is a well-investigated histamine H3 receptor inverse agonist/antagonist.Ciproxifan presynaptically inhibits glutamate release in rat hippocampus.

Ethyl Pyruvate; from Liver Preservation Solutions University of Wisconsin (UW) Increases the Effectiveness of the Solution.

BACKGROUND: The most important factor affecting the success rate of liver transplants is the preservation of the normal histologic and biochemical properties of the cells in the tissue taken. The study aimed to identify the possible increase in efficacy of ethyl pyruvate, which has a hepatoprotective effect, on the University of Wisconsin (UW) solution. METHODS: Rats were randomly selected and divided into 4 groups. After a laparotomy, the small intestines were removed from the abdomen and the portal pedicle was identified. Arterial and venous circulation of the liver was interrupted. After the portal vein was cannulated (and the distal of the portal pedicle was ligated, the liver was perfused with a solution. Perfusion solution was selected as Ringer Lactate in Group 1. In group 2, UW solution was chosen as the perfusion solution. In Group 3, the perfusion solution was chosen as the UW solution, but ethyl pyruvate at a dose of 40 mg/kg was administered intraperitoneally to the experimental animals 30 minutes before hepatectomy. In Group 4, as a perfusion solution, a UW solution with 40 mg/kg dose of ethyl pyruvate added to it was used. RESULTS: With TUNEL and Caspase-3 staining, a significant decrease was found in the apoptosis rates of Groups 2, 3, and 4 at the 12th hour post hepatectomy when compared with Group 1. When the morphometric liver sinusoid/parenchyma ratios and vena centralis diameters of the groups were examined, it was found that all preservation solutions containing the UW solution were more protective than the RL solution. CONCLUSIONS: Ethyl pyruvate is regarded as a promising agent that can increase the effect of the UW solution on organ preservation solutions. Because this study is the first in literature to apply ethyl pyruvate in preservation solutions, additional studies with larger series and different doses are needed.

LoxBlock-1 or Curcumin attenuates liver, pancreas and cardiac ferroptosis, oxidative stress and injury in Ischemia/reperfusion-damaged rats by facilitating ACSL/GPx4 signaling.

In this study, the effects of the pretreatment of Curcumin and LoxBlock-1 on liver, pancreas, and cardiac dysfunction following Ischemia-Reperfusion-induced (IR) Acute Kidney Injury (AKI) were investigated through the mechanisms of oxidative stress and ferroptosis. Total antioxidant status (TAS), total oxidant status (TOS) and oxidative stress index (OSI) parameters in the tissue were analyzed to investigate the oxidative stress occurring in the liver, pancreas, and heart, and Acyl-Coa synthetase long-chain family member (ACSL4). Glutathione peroxidase 4 (GPx4) enzyme levels were also analyzed by ELISA to investigate the effect on ferroptosis. In addition, hematoxylin-eosin staining was performed for histopathological examination of the tissues. As a result of biochemical analyzes, it was observed that oxidative stress parameters increased significantly in the IR group. In addition, while the ACSL4 enzyme level increased in the IR group in all tissues, the GPx4 enzyme level decreased. In the histopathological examination, it was observed that IR caused serious damage to the heart, liver, and pancreas tissues. The present study shows that Curcumin and LoxBlock-1 have a protective effect on the liver, pancreas, and cardiac ferroptosis following the effect on AKI. In addition, Curcumin was found to be more effective than LoxBlock-1 in I/R injury with its antioxidant property.

Probiotics ameliorates LPS induced neuroinflammation injury on Aß 1-42, APP, γ-ß secretase and BDNF levels in maternal gut microbiota and fetal neurodevelopment processes.

The gut microbiota influences brain development and functioning through the gut-brain axis. This is first study regulate maternal gut microbiota and fetal neurodevelopment processes by using probiotics such as Bifidobacterium bifidum (BIF) and Lactobacillus salivarius (LAC) in the prenatal period. In this study, Wistar Albino female rats were divided into five groups; Control, lipopolysaccharide (LPS, 100 µg/kg), LPS + LAC, LPS + BIF and LPS + LAC + BIF (4 × 109 ml CFU). Maternal rats were given probiotics for 21 days. Inflammation was induced by lipopolysaccharide (LPS), on the 17th day of pregnancy. After birth, the brain tissues of the maternal and neonatal rats were removed and their blood was collected. Fecal calprotectin levels of pregnant rats were measured as an important biomarker in determining intestinal flora disruption. Calprotectin levels were high in LPS group (p < 0.05). Aß 1-42, APP, γ secretase and ß- secretase levels were higher in both maternal and neonatal LPS groups (p < 0.05). These levels were statistically decreased in the probiotic groups compared to the LPS group, as demonstrated in both biochemical and histological analyzes (p < 0.05). While BDNF mRNA expression decreased in LPS groups, APP level increased in the same group. The difference between groups in mRNA expressions in the neonatal brain tissues was similar to maternal brain tissues. What's more, BDNF/actin and APP/actin rates were proven by western blot and the damage caused by neuroinflammation in the brain tissue and the preservation of the intestinal microbiota were visualized histopathologically on the morphological structures in all groups. It will shed light on new therapeutic strategies for the impact of the use of probiotics on the neurodevelopmental processes of the neonatal against LPS-induced inflammatory responses and impaired gut microbiota in the prenatal period.

Effects of the probiotic, Lactobacillus rhamnosus GG, on ulcer pathogenesis, HSP70 stress protein and nitric oxide levels in stress induced ulcer.

Peptic ulcer is a gastric or duodenal mucosal injury; psychological stress may participate in development of the lesions. Heat shock protein-70 (HSP70) is a molecular chaperone that is responsible for cellular healing; it is an early biomarker of cellular damage. Nitric oxide (NO) is an intra- and intercellular messenger in the gastrointestinal system that protects mucosal integrity. Lactobacillus rhamnosus is among the microflora of the intestinal tract; it is resistant to gastric acidity. We investigated the efficacy of L. rhamnosus administration on ulcer pathogenesis, stress protein HSP70 and NO levels in experimental stress induced ulcer. The proton pump inhibitor, pantoprazole, was used for comparison with the gastroprotective effect of the probiotic. We administered 10 mg/kg pantoprazole and L. rhamnosus at doses of 3 × 108 cfu/ml (M1), 15 × 108 cfu/ml (M5), 30 × 108 cfu/ml (M10) to rats according to McFarland-1, McFarland-5, McFarland-10 standards, respectively. Rats were stressed by immobilization at 4 °C, then sacrificed. The pH, amounts of gastric mucus, NO and HSP70 levels were measured and the histological structure of stomach was assessed. We found increased NO levels in the M5 group and increased HSP70 expression in the pantoprazole group. Significant epithelial damage was observed in the stressed groups and minimal epithelial damage was observed in M5 group compared to controls. The probiotic, L. rhamnosus, may be useful for preventing stress induced ulcers.

The effects of N-acetylcysteine on experimentally created l-asparaginase-induced liver and pancreatic damage in rats.

In this study, oxidative stress marker (malondialdehyde, MDA) and antioxidant enzymes (glutathione (GSH), catalase (CAT)) levels in the liver and pancreas tissue and the histopathological effects of N-acetylcysteine (NAC) were investigated in l-asparaginase (l-ASP) induced liver and pancreatic damage in rats. Forty male albino rats were divided into four groups. The control group was intraperitoneally injected physiological saline (0.02 mL/g); NAC group was injected NAC (200 mg/kg, five days); l-ASP group was injected single-dose l-ASP (10,000 U/kg), and l-ASP + NAC group was injected NAC for five days following single-dose l-ASP (10,000 U/kg). The surgical operation was performed on all animals on the fifth day. There was no difference between the groups regarding tissue MDA, GSH, and CAT levels (p>.05, for all). In the group receiving NAC after l-ASP, there was a significant improvement in the liver and pancreas damage score than the l-ASP group. NAC was effective in reducing organ damage caused by l-ASP.

Conivaptan and Boric Acid Treatments in Acute Kidney Injury: Is This Combination Effective and Safe?

Acute kidney injury is still a worldwide clinic problem that affects kidney function and associated with high mortality risk. Unfortunately, approximately 1.7 million people are thought to die from acute kidney injury each year. Boron element is defined as an "essential trace element" for plants and thought to have a widespread role in living organisms. Boric acid, which is one of the important forms of boron, has been extensively discussed for both medicinal and nonmedicinal purposes. However, there is a lack of data in the literature to examine the relationship between boric acid and antidiuretic hormone (ADH) antagonism in kidney injury. Thus, we aimed to investigate the effects of conivaptan as an ADH antagonist and boric acid as an antioxidant agent on the post-ischemic renal injury process. In this study, the unilateral ischemia-reperfusion (I/R) injury rat model with contralateral nephrectomy was performed and blood/kidney tissue samples were taken at 6th hours of reperfusion. The effects of 10 mg/mL/kg conivaptan and 50 mg/kg boric acid were examined with the help of some biochemical and histological analyses. We observed that conivaptan generally alleviated the destructive effects of I/R and has therapeutic effects. Also of note is that conivaptan and boric acid combination tended to show negative effects on kidney function, considering the highest BUN (78.46 ± 3.88 mg/dL) and creatinine levels (1.561 ± 0.1018 mg/dL), suggesting possibly drug-drug interaction. Although it has reported that conivaptan can interact with other active substances, no experimental/clinical data on the possible interaction with boric acid have reported so far.

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

Interest in phytochemical therapy methods in the treatment of diabetes is increasing day by day. Although the antidiabetic and antioxidant effects of Cistus laurifolius L. (CL) have been mentioned, the systemic effects remain unknown. The present study aims at evaluating the antidiabetic effects of the CL aqueous extract via metformin on streptozotocin (STZ)-induced diabetic rats. Forty male Wistar 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 inflammatory pathways were comparatively investigated. In addition, nuclear factor-κB (NFκB), tumor necrosis factor-alpha (TNF-α), and interleukin (IL)-1ß 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%, and 31.4% in the total oxidant capacity, NFκB, TNF-α, IL-1ß, caspase3, and cytochrome c levels, respectively, compared to the diabetic group. Additionally, CL treatments showed a dose-dependent reduction in NFκB, TNF-α, and IL-1ß expression levels. A 250mg/kg CL treatment exhibited a greater increase (by 9.6%) in total antioxidant capacity than metformin. CL treatment provided histologically more improvement in the brain, heart, pancreas, spleen, liver, kidney, and testicular tissues compared to the metformin group. Our results suggest that the single treatment of CL aqueous extract at the low doses may have stronger short-term anti-diabetic effects than metformin. Therefore, further studies are needed regarding the long-term hypoglycemic effect or treatment of CL aqueous extract.

In vivo effects of Viscum album and probiotics against carbon tetrachloride-induced liver injury.

This study tested the possible protective and therapeutic effects of Viscum album extract and probiotics against carbon tetrachloride (CCl4)-induced acute/chronic liver injury. Male Wistar rats were assigned to seven groups: Control, acute CCl4, acute V. album + CCl4, acute V. album + Probiotics + CCl4, chronic CCl4, chronic CCl4 + V. album, and chronic CCl4 + V. album + Probiotics. Acute and chronic liver injuries were induced by 2 mg/kg CCl4 (i.p.) and 1 mg/kg CCl4 (i.p.), respectively. The extract and probiotics were administered daily to related groups. Serum enzyme activities, lipid profile, total protein, albumin, bilirubin, heme oxgenase-1 and 8-hydroxydeoxyguanosine levels were measured. Liver tissue sections stained with Hematoxylin-Eosin. Acute or chronic CCl4-exposure caused to significant changes in concentrations/activities of the measured parameters. The oral administration of extract and probiotics showed protective and therapeutic effects against CCl4-induced liver-injury. The supplementation of intestinal flora by the use of probiotics may enhance the efficacy of orally given therapeutic extracts.

Protective Effect of Boric Acid and Omega-3 on Myocardial Infarction in an Experimental Rat Model.

Boric acid and omega-3 are used as essential elements for both animal and human health. Many researchers have shown these beneficial effects on cardiac and inflammatory markers. This study aims to evaluate cardiac protective effect of boric acid and omega-3 against MI (myocardial infarction), probably due to the suppression of pro-inflammatory cytokines of natriuretic peptides in rats. Fifty male Sprague-Dawley rats were randomly divided into five groups: control, MI, MI+boric acid, MI+omega-3, and MI+boric acid+omega-3. Saline solution (2 ml/day), omega-3 (800 mg/kg/day), and boric acid (100 mg/kg/day)+omega-3 (800 mg/kg/day) were orally administered to the relevant groups throughout the 28 days. To constitute the MI model, the rats were exposed to isoproterenol-HCl (ISO) (200 mg/kg, S.C.) on the 27th and 28th. In the MI group, serum levels of CK-MB, BNP, and TNF-α are increased significantly. Also, ST waves and heart rates were higher in the MI than the control. These results demonstrate that biochemical results healed in MI+boric acid, MI+omega-3, and MI+boric acid+omega-3 groups compared MI group. ECG and light microscope results supported the findings as well. The statistical analysis showed that boric acid and/or omega-3 has protective effects on cellular damage in MI.

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 µg/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-α, 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.

An Experimental Comparison of the Analgesic and Anti-Inflammatory Effects of Safflower Oil, Benzydamine HCl, and Naproxen Sodium.

The study aims to establish how feasible a natural therapy option (safflower oil) is in the treatment of postoperative pain. Naproxen sodium has already been experimentally proven to be effective for this purpose. Accordingly, the analgesic and anti-inflammatory effects of safflower oil were compared with those obtained with benzydamine HCl and naproxen sodium. Forty-two, healthy, adult female rats of Wistar albino species were divided at random into six groups of seven rats. The intervention allocation was as follows: Group No. 1-physiological saline 0.9%; Group No. 2-safflower oil 100 mg/kg; Group No. 3-safflower oil 300 mg/kg; Group No. 4-benzydamine HCl 30 mg/kg; Group No. 5-benzydamine HCl 100 mg/kg; and Group No. 6-naproxen sodium 10 mg/kg. Following allocation of treatment, pain was induced experimentally and tested in various ways (hot plate test, tail-pinching test, and writhing test) and the efficacy of each treatment in providing peripheral and central analgesia was evaluated. The second stage consisted of providing different treatments to four groups (groups 7-10) of seven rats each, chosen at random. The allocations were as follows: Group No. 7-physiological saline 0.9%; Group No. 8-safflower oil 300 mg/kg; Group No. 9-benzydamine HCl 100 mg/kg; and Group No. 10-naproxen sodium 10 mg/kg. To create experimental inflammation, 2% formaldehyde was injected into the experimental animal's paw and the resulting edema was measured and recorded for a 10-day period. Edema inhibition was calculated as a percentage. The rats were sacrificed and the paw and stomach dissected for histopathological examination. The data were used for statistical analysis, using the Shapiro-Wilk, Kruskal-Wallis H test, and two-way analysis of variance. In the tail-pinching test, it was determined that a 300 mg/kg dose of safflower oil shows central spinal analgesic efficacy and this effect is close in magnitude to 10 mg/kg of the reference material, naproxen sodium. In the squirming test, it was observed that the 100 and 300 mg/kg doses of safflower oil had a peripheral analgesic effect when compared with the serum physiological (placebo) group. The peripheral efficacy of 300 mg/kg safflower oil was found to approximate that of 10 mg/kg naproxen sodium. In rats treated with benzydamine HCl 100 mg/kg, similar peripheral analgesic efficacy to naproxen sodium 10 mg/kg was noted. In the hot plate test, no difference in the analgesic efficacy between the various agents was found. The change in inhibition of edema between the 1st and 10th days was most marked in rats receiving naproxen sodium 10 mg/kg. A significant difference was determined in the safflower oil 300 mg/kg and benzydamine HCl 100 mg/kg groups (P < .001). Regarding histopathology findings in the rat paw, significant differences were seen in venous congestion between placebo and safflower oil 300 mg/kg and in inflammation between the control and benzydamine HCl 100 mg/kg groups. Regarding the histopathology findings in the rat stomach, significant differences were observed in venous congestion between placebo and safflower oil 300 mg/kg; in damage to the epithelium between placebo and safflower oil 300 mg/kg and between naproxen sodium 10 mg/kg and safflower oil; and in cell infiltration and development of edema between placebo and safflower oil 300 mg/kg. It is predicted that further research into safflower oil and benzydamine HCl will create opportunities to develop analgesic-anti-inflammatory therapeutics of a novel kind for the treatment of postoperative pain and inflammation.

The Role of Oxidative Stress, Renal Inflammation, and Apoptosis in Post Ischemic Reperfusion Injury of Kidney Tissue: the Protective Effect of Dose-Dependent Boric Acid Administration.

Ischemia/reperfusion (I/R) injury is associated with a strong inflammatory and oxidative stress response to hypoxia and reperfusion that impair organ function. We aimed to investigate the role of oxidative stress, renal inflammation, and apoptosis in the injury of the kidney tissue after ischemic reperfusion, and the protective effect of dose-dependent boric acid administration. For this purpose, 35 Sprague Dawley albino rats were divided into five groups of seven animals in each group: Sham, I/R and I/R + boric acid (BA) (i.p at doses of 50, 100, and 200 mg/kg). All animals underwent nephrectomy (the right kidney was removed) and were expected to recover for 15 days. After recovery, each animal received 45 min of ischemia. BA was injected intraperitoneally 10 min before reperfusion and a 24-h reperfusion procedure was performed. Sham group only underwent surgical stress procedure. In order to investigate the oxidative stress induced by I/R injury and antioxidant effects of different BA doses in the kidney tissue, TAS, TOS, MDA, SOD, CAT, and GSH levels were measured. DNA fragmentation, cytochrome C levels, caspase 3 activity were measured to determine apoptotic index in tissue. IL-6 and TNF-α levels were measured in the evaluation of inflammation. Hematoxylin-eosin and TUNEL staining was performed for histopathological examinations. As a result, increased oxidative stress, inflammation, and apoptosis after I/R were decreased with different doses of BA treatment. The application of high-dose BA was found to be lower in anti-apoptotic, anti-inflammatory, and antioxidant effects than in the low-dose groups.

A possible protective role of betain and omega-3 supplementation in traumatic brain injury.

INTRODUCTION: Due to irreversible damage following head trauma, many overlapping pathophysiological events occur including excitotoxicity, acidotoxicity, ionic imbalance, edema, oxidative stress inflammation and apoptosis. MATERIAL AND METHODS: In this this study, after the rats were separated in to groups theserats were fed throughout fourteen days with betaine, omega-3 or betaine+omega-3 combination in physiological limits prior to the trauma. After a closed head trauma, the damaged brain tissues were collected for biochemically and histologically analyses. This examination involved analyses of levels of caspase-3 and cytochrome C and neuron-specific enolase (NSE) levels in brain tissue. RESULTS: These analyses showed that traumatic brain injury (TBI) caused an increase in the levels of caspase-3, cytochrome C and neuron-specific enolase (NED) in the brain tissues examined. DISCUSSION: In this study, apoptotic and/or necrotic cell death via mitochondrial cytochrome C caspase pathway in traumatized cells and neuron-specific enolase (NED) increase indicative of neuronal damage confirmed the research hypothesis. CONCLUSION: Level of the biomarkers induced by brain injury in the groups fed with betaine, omega-3 and betaine+omega-3 combination before the traumatic damage approximated to that of control group values, suggesting that these products may have a neuroprotective role. KEY WORDS: Betain, Caspase-3, Cytochrome C and Neuron-specific enolase, Omega-3, Traumatic brain injury.

Beneficial effect of mirtazapine on diabetes-induced hyperalgesia: involvement of TRPV1 and ASIC1 channels in the spinal cord and dorsal root ganglion.

OBJECTIVES: Neuropathic pain reduces the life qualities of patients with Diabetes mellitus. Clinical guidelines recommend relief in diabetic neuropathic pain through the use of some antidepressants, anticonvulsants, opioids as well as capsaicin cream or lidocaine patches. However, since the majority of patients do not or partially respond to current treatments, there is a growing necessity for new drugs increasing the pain relief in patients with diabetes. Therefore, based on the therapeutic potential of antidepressants on neuropathic pain, we investigated the promising antihyperalgesic effect of mirtazapine (MRT) in painful diabetic neuropathy. METHODS: Experimental diabetes was induced in rats by single intraperitoneal injection of 55 mg/kg dose of streptozocin (STZ). After 4 weeks of injection of STZ, MRT was administrated for 14 days at 40 mg/kg dose. Randall-Selitto and Hargreaves tests were applied for paw-withdrawal threshold and paw-withdrawal latency measurement. TRPV1 and ASIC1 expressions measured by Western blot in dorsal root ganglion and spinal cord. RESULTS: Administration of MRT significantly improved both of the decreased paw-withdrawal threshold and shortened the paw-withdrawal latency of diabetic rats, respectively. Besides, increased levels of TRPV1 and ASIC1 channels in dorsal root ganglion and spinal cord of diabetic rats, evaluated by Western blot method, were decreased following the MRT treatment. DISCUSSION: These data show, for the first time, that MRT has beneficial effects against diabetes-induced hyperalgesia, and that suppressive effect of this drug on TRPV1 and ASIC1 levels, which are increased in diabetic rats, may be some of the pharmacological mechanisms underlying the exhibited antihyperalgesic effect of MRT.