Intracerebroventricular administration of the exercise hormone irisin or acute strenuous exercise alleviates epileptic seizure-induced neuroinflammation and improves memory dysfunction in rats.

BACKGROUND: Status epilepticus is a common and potentially life-threatening neurological emergency with a high risk for cognitive and neurobiological impairment. Our aim was to evaluate the neuroprotective effects of centrally administered irisin and acute exhausting exercise against oxidative brain injury and memory dysfunction due to a pentylenetetrazole (PTZ)-induced single seizure. Male Sprague Dawley rats with intracerebroventricular (icv) cannulas were randomly divided into intraperitoneally (ip) saline-injected control and PTZ-injected (45 mg/kg) seizure groups. Both the control and PTZ groups were then treated with irisin (7.5 µg/kg, 2 µl, icv), saline (2 µl, icv) or were forced to an acute bout of strenuous exercise before the ip injection of saline (control) or PTZ. Seizures were evaluated using the Racine score. To evaluate memory performance, a passive avoidance test was performed before and after PTZ injection. Following euthanasia at the 24th hour of seizure induction, brain tissues were removed for histopathological examination and for evaluating oxidative damage, antioxidant capacity, and neurotransmitter levels. RESULTS: Glutamate/GABA imbalance observed in PTZ rats was corrected by irisin administration (p < 0.001/p < 0.01), while irisin prevented the generation of reactive oxygen species and lipid peroxidation (p < 0.05 - 0.001) and replenished the antioxidant catalase and glutathione levels (p < 0.01-0.01) in the cerebral tissue, and reduced the histologically evident neuronal injury due to a single seizure (p < 0.05 - 0.01). Irisin also delayed the onset of seizures (p < 0.05) and improved memory dysfunction (p < 0.05), but did not affect the severity of seizures. The acute exhaustive swimming exercise completed before PTZ-seizure depressed glutamate level (p < 0.001), maintained the oxidant/antioxidant balance, alleviated neuronal injury (p < 0.05 - 0.01) and upregulated cerebral BDNF expression (p < 0.05). CONCLUSION: In conclusion, acute high-intensity exercise or exogenously administered irisin provides neuroprotection by maintaining the balance of excitatory/inhibitory neurotransmitters and oxidant/antioxidant systems.

Early Prediction of Bloodstream Infection with Complete Blood Count Parameters: an Ex-Vivo Human Whole Blood Model.

BACKGROUND: Despite the advanced laboratory technologies available today, blood culture is the gold standard method in the diagnosis of bloodstream infections. Automated blood culture devices give blood culture results for laboratories approximately in 2 - 3 days up to 7 days. Moreover, some microorganisms like nonreproducible bacteria, fungi or viruses cannot be produced in culture. Among all samples taken for blood culture on suspicion of infection approximately 10% are determined as positive whereas the false positive rate due to contamination is 5%. Especially in life-threatening severe conditions such as sepsis early diagnosis and prompt treatment are crucial. Based on this the aim of this study is to investigate complete blood count parameters as potential early markers in Escherichia coli, Staphylococcus aureus and Candida albicans bloodstream infections using an ex vivo whole blood model. METHODS: Blood samples collected from healthy donors (n = 10) were treated with suspensions containing a certain concentration of microorganisms (107 CFU/mL for both E. coli ATCC 25922 and S. aureus ATCC 29213, 106 CFU/mL for C. albicans ATCC 14053). After bacteremia and candidemia were induced, complete blood count parameters were analyzed hourly in the samples until the end of the 4th hour with a Mindray BC-6800 hematology analyzer. Statistical analysis was performed by Tukey-Kramer post-hoc multiple comparison test and statistical significance was accepted as p < 0.05. RESULTS: When platelet derived parameter baseline values were compared to hourly values in E. coli and S. aureus induced whole blood samples, it was found that the decrease in PLT, P-LCC and the increase in IPF% was significant from the first hour whereas the increase in IMG% was found to be significant only from the 3rd hour onward. In the experiments with C. albicans, it was observed that the increase in IPF% and IMG% was significant from the 2nd and 3rd hour onward, respectively. There was no relationship between MPV, P-LCR, and NLR baseline and hourly results in any microorganism induced model. CONCLUSIONS: IPF% can guide clinicians in the early diagnosis and management of treatment of infections caused by S. aureus, E. coli, and C. albicans.

Possible anti-inflammatory, antioxidant, and neuroprotective effects of apigenin in the setting of mild traumatic brain injury: an investigation.

OBJECTIVE: Apigenin is a plant flavone proven with biological properties such as anti-inflammatory, antioxidant, and antimicrobial effects. This study, it was aimed to examine the possible anti-inflammatory, antioxidant, and neuroprotective effects of apigenin in the setting of the mild traumatic brain injury (TBI) model. METHODS: Wistar albino male rats were randomly assigned to groups: control (n = 9), TBI (n = 9), TBI + vehicle (n = 8), and TBI + apigenin (20 and 40 mg/kg, immediately after trauma; n = 6 and n = 7). TBI was performed by dropping a 300 g weight from a height of 1 m onto the skull under anesthesia. Neurological examination and tail suspension tests were applied before and 24 h after trauma, as well as Y-maze and object recognition tests, after that rats were decapitated. In brain tissue, luminol- and lucigenin-enhanced chemiluminescence levels and cytokine ELISA levels were measured. Histological damage was scored. Data were analyzed with one-way ANOVA. RESULTS: After TBI, luminol (p < .001) and lucigenin (p < .001) levels increased, and luminol and lucigenin levels decreased with apigenin treatments (p < .01-.001). The tail suspension test score increased with trauma (p < .01). According to the pre-traumatic values, the number of entrances to the arms (p < .01) in the Y-maze decreased after trauma (p < .01). In the object recognition test, discrimination (p < .05) and recognition indexes (p < .05) decreased with trauma. There was no significant difference among trauma apigenin groups in behavioral tests. Interleukin (IL)-10 levels, one of the anti-inflammatory cytokines, decreased with trauma (p < .05), and increased with 20 and 40 mg apigenin treatment (p < .001 and p < .01, respectively). The histological damage score in the cortex was decreased in the apigenin 20 mg treatment group significantly (p < .05), but the decrease observed in the apigenin 40 mg group was not significant. CONCLUSION: The results of this study revealed that apigenin 20 and 40 mg treatment may have neuroprotective effects in mild TBI via decreasing the level of luminol and lucigenin and increasing the IL-10 levels. Additionally, apigenin 20 mg treatment ameliorated the trauma-induced cortical tissue damage.

Targeting soluble guanylate cyclase with Riociguat has potency to alleviate testicular ischaemia reperfusion injury via regulating various cellular pathways.

Testicular ischaemia reperfusion (I/R) injury results with serious dysfunctions in testis. This study aims to explore effects of soluble guanylate cyclase (sGC) stimulator Riociguat on experimental testicular I/R injury in rats. Twenty-one male rats were divided into three groups (Control, IR and IRR). The control group was not exposed to any application. Bilateral testis from IR and IRR animals were rotated 720° in opposite directions for 3 h to induce experimental testicular ischaemia. Animals in IR and IRR groups were subjected to 3 h of reperfusion. Isotonic and Riociguat were administered to the animals 30 min prior reperfusion by oral gavage. At the end of experiment, animals were sacrificed and tissue samples were used for analyses. Riociguat treatment significantly decreased tissue malondialdehyde and Luminol levels compared to the IR group (p < 0.05). The pathological changes, pro-apoptotic proteins (Bax, Caspase 3, and Caspase 9) and apoptotic index in the IR group were down regulated in Riociguat treated animals (p < 0.05). Riociguat treatment was also significantly increased anti-apoptotic Bcl-2 expression, but alleviated tissue injury via modulating pro-inflammatory cytokine IL-1ß levels and significantly (p < 0.05) down-regulating NF-κB activity. Moreover, mTOR and ERK phosphorylation increased in IR group (p < 0.05), but Riociguat treatment reduced protein phosphorylation. Our experiment indicated that targeting sGC might support surgical interventions in testicular I/R injury by modulating oxidative stress, inflammation, and apoptotic protein expression levels, but more detailed studies are required to explore the protective activity of Riociguat and underlying mechanisms in testicular I/R injury.

Paraoxonase-1 and fetuin-A levels in children with cerebral palsy.

BACKGROUND: Studies mostly focused on risk factors and clinical status in children with cerebral palsy (CP). Various antiinflammatory markers may help us in the early diagnosis and clinical classification of cerebral palsy patients. In this study, the relationship between antiinflammatory marker levels and clinical status in patients with CP is determined. It is the first time that Fetuin-A and Paraoxonase-1 (PON-1) are examined in children with CP. METHODS: The study is conducted on 79 children which are divided into two groups as CP and control. Gross motor function and spasticity are evaluated in addition to biochemical parameters. RESULTS: There is a statistically significant difference between CP and control group in terms of PON-1 activity, high sensitive C-Reactive Protein, HDL, and total cholesterol levels. There is no statistically significant difference in Fetuin A levels between the two groups. DISCUSSION: In suspected CP patients less than 24 months of age who possess prenatal and postnatal risk factors, the determination of PON-1 activity can be considered as a biomarker to support early diagnosis.

Oestrogen receptor ERα and ERß agonists ameliorate oxidative brain injury and improve memory dysfunction in rats with an epileptic seizure.

NEW FINDINGS: What is the central question of this study? Could different hormonally active substances, including oestrogen receptor (ER) agonists, protect against oxidative brain damage and memory impairment induced by a single epileptic seizure in rats? If so, which signalling mechanisms are involved in their anti-inflammatory effects? What is the main finding and its importance? Chronic administration of oestrogen, progesterone, ER modulators/agonists or blockade of testosterone exhibited anti-inflammatory and antioxidant actions on single seizure-induced neuronal injury, while ER agonists additionally improved memory function and up-regulated CREB signalling and hippocampal GABA(A)α1 receptor density, suggesting that ERα or ERß receptor activation may be beneficial in protecting against seizure-related oxidative brain injury and cognitive dysfunction. ABSTRACT: The susceptibility to epileptic seizures is dependent on sex as well as fluctuations in oestrogen levels, while exogenous oestrogen was shown to have no effect or to facilitate or to inhibit seizure activity. Oestrogen receptors (ERs) mediate antioxidant and anti-inflammatory actions in several inflammatory models, but the involvement of ERs in seizure-induced neuronal injury has not been evaluated previously. In order to assess the effects of resveratrol, progesterone, oestradiol (E2), an anti-testosterone (cyproterone acetate; CPA), a selective ER modulator (tamoxifen; TMX) and ERα/ERß agonists (propyl pyrazole triol (PPT), diarylpropionitrile (DPN)) on oxidative brain damage and memory impairment due to epileptic seizure, male Wistar rats (n = 120) received one of the treatment choices either in drinking water or intraperitoneally for 31 days, and epileptic seizure was induced on the 28th day by injection of a single-dose of pentylenetetrazole (45 mg kg-1 ). The results demonstrate that chronic pretreatment with resveratrol, progesterone, E2, CPA or TMX suppressed most of the inflammatory parameters indicative of oxidative neuronal injury, while treatment with the ER agonists DPN or PPT were found to be even more effective in limiting the oxidative damage. Treatment with DPN resulted in the up-regulation of cAMP response element-binding protein (CREB) and brain-derived neurotrophic factor (BDNF) expression, while PPT up-regulated expression of CREB without affecting BDNF levels. Moreover, both ER agonists provided protection against seizure-induced memory loss with a concomitant increase in hippocampal GABA(A)α1-positive cells. In conclusion, ER agonists, and more specifically ERß agonist, appear to provide maximum protection against seizure-induced oxidative brain injury and associated memory dysfunction by up-regulating the expression of CREB, BDNF and GABA(A)α1 receptors.

Potential Effect of 1,25 Dihydroxyvitamin D3 on Thioacetamide-Induced Hepatotoxicity in Rats.

BACKGROUND: 1,25 Dihydroxyvitamin D3 (1,25(OH)2D3) modulates inflammation and immune responses. Deficiency of 1,25(OH)2D3 was found to be associated with the risk of cancer, cardiovascular disease, osteoarthritis, infections, and autoimmune diseases. This study evaluated the effect of 1,25 dihydroxyvitamin D3 1,25(OH)2D3 on thioacetamide (TAA)-induced acute liver injury in rats. MATERIALS AND METHODS: Rats were treated with either saline or 1,25(OH)2D3 (0.30 µg/kg; orogastrically) for 15 d. Starting from day 13, TAA (200 mg/kg; intraperitoneally) was given for 3 d. On day 15, all rats were euthanized. Liver and blood samples were collected. RESULTS: TAA caused severe damage, increased lipid peroxidation with reductions in endogenous antioxidants, increased apoptosis, increased production of reactive oxygen species, and elevated inducible nitric oxide synthase (iNOS), and nuclear factor kappa B (NF-κB) expression in liver. Extent of damage was decreased by 1,25(OH)2D3 (P < 0.01). 1,25(OH)2D3 attenuated the increase in malondialdehyde (P < 0.01), increase in myeloperoxidase (P < 0.01), increase in chemiluminescence levels (P < 0.05) and apoptotic activity (P < 0.001). Elevated liver iNOS and NF-κB expression in TAA group was also reduced by 1,25(OH)2D3 (P < 0.001, for iNOS; P < 0.001, for NF-κB). TAA group revealed high serum aspartate transaminase and alanine transaminase (ALT) activities (P < 0.01, for aspartate transaminase; P = 0.08, for ALT) and reduced albumin levels (P < 0.01) compared with control. 1,25(OH)2D3 had no statistically significant effect on these parameters. CONCLUSIONS: 1,25(OH)2D3 provides protection against hepatic injury in a rat model of TAA-induced hepatotoxicity via suppression of inflammatory reaction, oxidative stress, and apoptosis.

The effects of antibiotics and melatonin on hepato-intestinal inflammation and gut microbial dysbiosis induced by a short-term high-fat diet consumption in rats.

High-fat diet (HFD) consumption leads to metabolic disorders, gastrointestinal dysfunction and intestinal dysbiosis. Antibiotics also disrupt the composition of intestinal microbiota. The aim of the present study was to investigate the impact of a short-term feeding with HFD on oxidative status, enteric microbiota, intestinal motility and the effects of antibiotics and/or melatonin treatments on diet-induced hepato-intestinal dysfunction and inflammation. Male Sprague-Dawley rats were pair-fed with either standard chow or HFD (45 % fat) and were given tap water or melatonin (4 mg/kg per d) or melatonin plus antibiotics (ABX; neomycin, ampicillin, metronidazole; each 1 g/l) in drinking water for 2 weeks. On the 14th day, colonic motility was measured and the next day intestinal transit was assessed using charcoal propagation. Trunk blood, liver and intestine samples were removed for biochemical and histopathological evaluations, and faeces were collected for microbiota analysis. A 2-week HFD feeding increased blood glucose level and perirenal fat weight, induced low-level hepatic and intestinal inflammation, delayed intestinal transit, led to deterioration of epithelial tight junctions and overgrowth of colonic bacteria. Melatonin intake in HFD-fed rats reduced ileal inflammation, colonic motility and perirenal fat accumulation. ABX abolished increases in fat accumulation and blood glucose, reduced ileal oxidative damage, suppressed HFD-induced overgrowth in colonic bacteria, and reversed HFD-induced delay in intestinal transit; however, hepatic neutrophil accumulation, hepatic injury and dysfunction were further enhanced. In conclusion, the results demonstrate that even a short-term HFD ingestion results in hepato-intestinal inflammatory state and alterations in bacterial populations, which may be worsened with antibiotic intake, but alleviated by melatonin.

Ameliorative effects of riboflavin on acetic acid-induced colonic injury in rats.

Riboflavin (RF) has been found to be a promising antioxidant and/or anti-inflammatory agent in several studies. However, the effect of RF against acetic acid (AA)-induced colonic injury is currently unknown. This study aimed to investigate the potential antioxidant and protective effects of RF in a rat model of ulcerative colitis. Starting immediately after the colitis induction (AA+RF group) or 1 week before the colitis induction (RF+AA+RF group), the rats were treated with RF (25 mg/kg per day; p.o.) for 3 days. The control and AA groups received saline (1 mL; p.o.) whereas AA+SS group (positive control) received sulfasalazine (100 mg/kg per day; p.o.) for 3 days. Colonic samples were taken for the biochemical and histological assessments on the third day. High damage scores, elevated tissue wet weight index (WI), tissue myeloperoxidase (MPO) activity, 8-hydroxy-2'-deoxyguanosine levels and chemiluminescence values, and a pronounced decrease in antioxidant glutathione (GSH) levels of the AA group were all reversed by RF pretreatment (RF+AA+RF group) and SS treatment (AA+SS group) (P < .05-.001). Tissue WI, MPO activity and GSH levels were not statistically changed in the AA+RF group. Western blot analysis revealed that the decreased protein expressions of tissue collagen (COL) 1A1, COL3A1 and transforming growth factor-ß1 in the AA group were elevated in all the treatment groups (P < .05-.001). In conclusion, RF exerts both the antioxidant and anti-inflammatory effects against AA-induced colonic inflammation by suppressing neutrophil accumulation, inhibiting reactive oxidant generation, preserving endogenous glutathione, improving oxidative DNA damage and regulating inflammatory mediators, suggesting a future potential role in the treatment and prevention of ulcerative colitis.

Halofuginone improves caustic-induced oxidative injury of esophagus in rats.

BACKGROUND: The aim of this study is to evaluate the anti-inflammatory and anti-fibrotic effects of halofuginone in caustic esophageal burn injury in rats. MATERIALS AND METHODS: Corrosive esophageal injury (CEI) was produced in male Wistar albino rats by instilling NaOH solution (1 ml, 37.5%) into the distal esophagus. Rats were decapitated on the 3rd day (early group) or 28th day (late group), and treated daily with either saline or halofuginone (100 µg/kg/day; i.p.), continued on alternate days after the third day. Histopathological evaluation and measurement of nitric oxide (NO), peroxynitrite (ONOO-) and oxygen-derived radicals by chemiluminescence (CL) were made in the distal 2 cm of the esophagus. Non-irrigated proximal esophageal samples were assessed for the levels of nuclear factor (NF)-κB, caspase-3, glutathione (GSH), malondialdehyde (MDA) and myeloperoxidase (MPO) activity. RESULTS: GSH, MDA, NF-κB and caspase-3 levels, and MPO activity in the proximal esophagus were not different among groups. Increased number of TUNEL (+) cells in the irrigated esophagus of the early and late caustic injury groups was reduced by halofuginone treatment. High microscopic damage scores in both early and late CEI groups were decreased with halofuginone treatment. NO, ONOO- and CL levels, which were elevated in the saline-treated early CEI group, were reduced by halofuginone treatment, but reduced NO and ONOO- levels in the late period of saline-treated group were increased by halofuginone. CONCLUSION: In addition to its anti-fibrotic effects, current findings demonstrate that halofuginone exerts antioxidant and anti-apoptotic actions and supports therapeutic potential for halofuginone in CEI-induced oxidative stress.

Protective effect of alpha-lipoic acid, aerobic or resistance exercise from colitis in second hand smoke exposed young rats.

The role of second hand smoke (SHS) exposure on ulcerative colitis is not known. Our aim was to examine the effects of α-lipoic acid (ALA), chronic aerobic (AE) or resistance exercise (RE) on SHS exposed rats with colitis. Sprague-Dawley male rats (150-200 g, n=54) were selected for colitis induction. Among the colitis groups, one group was exposed to SHS (6 d/wk, 4 cigarettes/d) and the other was not. The SHS group was divided into subgroups as follows: sedentary; AE (swimming; 3 d/wk); and RE (climbing with weight; 3 d/wk). After 5 weeks, colitis was induced by intrarectal acetic acid. All groups had subgroups that were given subcutaneously ALA (50 mg/kg per day) or vehicle for 3 days. Following decapitation, colon tissues were sampled to examine malondialdehyde (MDA) and glutathione (GSH) levels, myeloperoxidase (MPO) activity, luminol and lucigenin chemiluminenscence, macroscopic scoring and histologic examination. ANOVA and Student's t-test were used for statistical analysis. The increased macroscopic and microscopic scores, MPO, MDA, luminol and lucigenin measurements in colitis and SHS-colitis groups were decreased via ALA (P<.05-.001). AE declined macroscopic and microscopic scores, MDA, lucigenin compared to colitis and SHS-colitis groups (P<.01-.001). RE reduced microscopic score, MPO, MDA, luminol, lucigenin (P<.05-.001) that were increased with colitis. Decreased GSH levels (P<.01) in the SHS-colitis group approached to control levels when given ALA. According to our results SHS and colitis induction increased inflammatory damage. SHS did not worsen it more than colitis. Our results suggest that ALA, AE or RE might be protective for SHS exposed ulcerative colitis conditions.

Nesfatin-1 alleviates gastric damage via direct antioxidant mechanisms.

BACKGROUND: Indomethacin is a nonsteroidal anti-inflammatory drug, which is known to produce serious side effects, causing ulcerative lesions. Nesfatin-1, a newly identified anorexigenic peptide, was recently shown to have neuroprotective effects. The aim of the study was to investigate the anti-inflammatory effects of nesfatin-1 on indomethacin-induced gastric ulcer. MATERIALS AND METHODS: After a 24-h starvation period, ulcer was induced in Sprague-Dawley rats by subcutaneous administration of indomethacin (25 mg/kg), whereas control group received vehicle. Fifteen minutes after ulcer induction, rats were treated with either saline or nesfatin-1 (0.1, 0.3, or 1 µg/kg, intraperitoneally). At the fourth hour, all rats were decapitated and their trunk blood was collected for tumor necrosis factor (TNF)-α and interleukin (IL)-6 measurements. Stomach samples were examined microscopically and analyzed for myeloperoxidase (MPO) activity, malondialdehyde (MDA), glutathione (GSH), luminol-, and lucigenin-enhanced chemiluminescence (CL) levels. RESULTS: Ulcer induction increased serum TNF-α; and IL-6 levels, gastric CL and MDA levels and MPO activity but decreased gastric GSH content (P < 0.05-0.001). On the other hand, 0.1 µg/kg dose of nesfatin-1 reduced microscopic and macroscopic damage scores, decreased MPO activity and MDA levels, CL and IL-6 levels, whereas gastric GSH was replenished (P < 0.01). However, indomethacin-induced increase in TNF-α level was abolished at only 1 µg/kg dose of nesfatin-1 (P < 0.01). CONCLUSIONS: Nesfatin-1 alleviated indomethacin-induced gastric injury, suggesting that the anti-inflammatory and gastroprotective effects of nesfatin-1 on oxidative gastric damage could be implemented by supporting the balance in oxidant and antioxidant systems while inhibiting the generation of pro-inflammatory mediators.

Comparison of Dietary Supplementation with Krill Oil, Fish Oil, and Astaxanthin on an Experimental Ethanol-Induced Gastric Ulcer Model: A Biochemical and Histological Study.

BACKGROUND/OBJECTIVES: Despite advances in ulcer treatment research, the search for new, safe, and effective strategies for preventing and treating ulcer diseases persists. METHODS: In this study, the protective effects of dietary supplementation with krill oil (KO), fish oil (FO), and astaxanthin (ASX) on an ethanol-induced gastric ulcer model were compared during biochemical and histological observations. Sprague-Dawley (n = 64) rats randomly divided into four groups-normal control (vehicle), KO, FO, and ASX groups-received the supplements via the orogastric route at a rate of 2.5% (v/w) of their daily feed consumption for 4 weeks. Then, ulcer induction was performed with ethanol. RESULTS: The ulcer group showed increased levels of malondialdehyde (MDA), chemiluminescence (CL), and myeloperoxidase (MPO) activity and decreased levels of glutathione in the gastric tissues. While KO, FO, and ASX supplementation decreased chemiluminescence levels in the ulcer group, only ASX supplementation decreased MDA levels and MPO activity. CONCLUSIONS: In conclusion, supplementation with KO or FO has a similar protective effect against ethanol-induced ulcer damage, as it inhibits ROS formation and reduces lipid peroxidation. However, ASX supplementation has a higher protective effect than KO or FO supplementations against experimental ethanol-induced gastric lesions in rats, as it inhibits ROS formation and reduces neutrophil infiltration and lipid peroxidation.

Neuropeptide W protects against ovarian oxidative injury and reinforces ovarian steroidogenic activity via the upregulation of ERα expression.

OBJECTIVES: The aim of this study was to investigate the protective effect of neuropeptide W (NPW) on ovarian ischemia-reperfusion-induced oxidative injury and ovarian steroid metabolism. METHODS: Rats were randomly divided into control and ischemia groups that received either saline or NPW (0.1 or 5 µg/kg/day). Bilateral ovarian ischemia was performed for 3 h followed by a 72-h reperfusion. Blood, ovary, and uterus samples were collected for biochemical and histological assessments. KEY FINDINGS: Treatment with either dose of NPW alleviated oxidative injury of the ovaries with a significant suppression in free radical formation and decreased histopathological injury in both the ovarian and uterine tissues, along with reduced lipid peroxidation and neutrophil accumulation in the uterus. Moreover, NPW treatment reversed the decrease in aromatase expression with a concomitant reduction in the expression of the inactivity enzyme estrogen sulfotransferase. Also, downregulation of estrogen receptor-α (ERα) expression in the injured ovarian tissue was abolished by NPW treatment, which implicates that the protective effect of NPW on the female reproductive system may involve the upregulation of the ERα-mediated signaling pathway. CONCLUSIONS: Our study demonstrated for the first time that NPW protects against ovarian oxidative injury and reinforces ovarian steroidogenic activity, which is accompanied by the upregulation of ERα expression in the ovaries.

Regulation of STAT3 and NF-κB signaling pathways by trans-Anethole in testicular ischemia-reperfusion injury and its gonadoprotective effect.

Testicular ischemia reperfusion (I/R) injury is a significant urological problem where clinical interventions may be inadequate, and the antioxidants might be potential co-treatment modalities. This study examined the gonadoprotective effect of trans-Anethole in testicular I/R injury. Twenty-eight male rats were divided into four groups. Rats in the I/R, I/R + t100, I/R + t200 groups underwent bilateral testicular I/R injury. The I/R + t100 and I/R + t200 groups received 100 or 200 mg/kg trans-Anethole at the 2nd hour of ischemia. Microscopic evaluations demonstrated that testicular I/R injury leads to severe testicular degeneration. Tissue oxidative stress, pro-apoptotic Bcl-2 associated X (Bax) and Caspase 3, pro-inflammatory Tumor necrosis factor-alpha (TNF-α), Interleukin-1 beta (IL-1ß) and Interleukin 6 (IL-6) cytokines levels were significantly (p < 0.05) upregulated when compared to the Control group. Additionally, transcription factors Signal transducer and activator of transcription 3 (STAT3) and Nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) levels increased significantly (p < 0.05) compared to the Control group. Tissue disrupted parameters in the I/R + t200 group were significantly different (p < 0.05) from the I/R group, contrasting with the slight improvement in the I/R + t100 group. The STAT3 and NF-κB expression levels in the I/R + t200 group were significantly suppressed (p < 0.05) compared to the I/R group. In conclusion, our study indicates that trans-Anethole could enhance gonadoprotective activity in testicular I/R injury, potentially involving transcription factors STAT3 and NF-κB. However, before the consumption of trans-Anethole-containing natural or manufactured goods, the potential benefits and side effects should be carefully evaluated.

Gilaburu (Viburnum opulus L.) fruit extract has potential therapeutic and prophylactic role in a rat model of acetic acid-induced oxidant colonic damage.

ETHNOPHARMACOLOGICAL RELEVANCE: Ulcerative colitis (UC) which has a global impact on the health care system with its recurrent and incompletely curable characteristics, affects the patients' quality of life. Gilaburu (GB; Viburnum opulus L.) is a fruit with rich polyphenol ingredient which is used ethnobotanically in Türkiye for medicinal purposes (for example, to pass kidney stones, to treat stomach, heart, and liver diseases, hemorrhages, hypertension, ulcers, common cold, tuberculosis, rheumatic and menstrual pain, and diabetes). On the other hand, the effects of GB in the experimental UC model have not been studied. AIM OF THE STUDY: This study aimed to explore the potential antioxidant and anti-inflammatory effects of GB fruit extract in improving acetic acid (AA)-induced UC. MATERIALS AND METHODS: Starting immediately after (AA + GB group) or 1 week before (GB + AA + GB group) the colitis induced by intrarectal AA (5%; v/v) administration, the rats orally received GB (100 mg/kg) once per day for 3 days. The control and AA groups were administered orally saline (1 ml), while the AA + SS group were administered sulfasalazine (SS; 100 mg/kg; orally) as a positive control once per day for 3 days. Distal colonic tissue specimens were obtained for the histological and biochemical [myeloperoxidase (MPO), malondialdehyde (MDA), glutathione (GSH), chemiluminescence (CL), caspase-3, 8-hydroxy-2'-deoxyguanosine (8-OHdG), matrix metalloproteinase (MMP)-9, transforming growth factor (TGF)-ß1, smad-3 and cytokine (tumor necrosis factor (TNF)-α, interleukin (IL)-1ß, IL-6, IL-8, interferon (IFN)-γ), measurements] evaluations on the 3rd day. RESULTS: Elevated macroscopic and microscopic damage scores, high tissue wet weight values, increased tissue-associated MPO, MDA, CL, caspase-3, 8-OHdG, cytokines (TNF-α, IL-1ß, IL-6, IL-8), MMP-9, TGF-ß1, smad-3 levels, and decreased GSH values of the AA group were all reversed by GB treatments (AA + GB and GB + AA + GB groups) (p < 0.05-0.001). However, sulfasalazine treatment (AA + SS group) did not change the IL-8, 8-OHdG, MMP-9, and TGF-ß1 measurements significantly. CONCLUSIONS: Gilaburu shows both anti-inflammatory and antioxidant effects against AA-induced colonic damage by suppressing neutrophil infiltration, regulating inflammatory mediators, inhibiting reactive species production, lipid peroxidation, and apoptosis, conserving endogenous antioxidant glutathione, and ameliorating oxidative DNA damage. Since the current ulcerative colitis drugs display limited benefits and adverse side effects, potential therapeutic and/or prophylactic role of gilaburu can be evaluated in ulcerative colitis.

Protein kinase C activation causes neurite retraction via cyclinD1 and p60-katanin increase in rat hippocampal neurons.

Neurons are differentiated postmitotic cells residing in G0 phase of the cell cycle and are unable to proceed through G1 phase, in which cyclinD1 needs to be up-regulated for initiation. Yet, a growing body of evidence has shown that cell cycle re-activation via cyclinD1 up-regulation drives neurons into apoptosis. By contrast, there is also evidence demonstrating cell cycle proteins playing roles in neuronal differentiation. cyclinD1 has been shown to be differently regulated by protein kinase C alpha (PKC-α) in various mitotic cells. Based on these different effects, we investigated the role of PKC-α on cyclinD1 regulation in hippocampal neurons. Neurons were treated with PKC activator, PMA, and analysed for subcellular distributions of PKC-α and cyclinD1. Remarkably, PMA treatment increased nuclear PKC-α and cyclinD1, but not PKC-ε in hippocampal neurons. Increases in nuclear PKC-α and cyclinD1 were accompanied by microtubule re-organisation via increases in tau and retinoblastoma protein phosphorylation levels. Increased p60-katanin and p53 changed the neuronal morphology into neurons with shorter, but increased number of side branches. Since up-regulation of cell cycle is associated with apoptosis in neurons, we also analysed changes in Bax, Bcl-2 early and PARP (poly(ADP-ribose)polymerase), caspase3 late apoptotic markers. However, we did not observe any indication of apoptosis. These data suggest that in addition to their previously known roles in mitotic cells on cell cycle regulation, PKC-α and cyclinD1 seem to be important for differentiation, and nuclear PKC-α and cyclinD1 interfere with differentiation by promoting microtubule re-organisation through PKC signaling without triggering apoptosis.

Lipid peroxidation and paraoxonase activity in nocturnal cyclic and sustained intermittent hypoxia.

PURPOSE: Obstructive sleep apnea (OSA) and chronic obstructive pulmonary disease (COPD) have been known to be associated with atherosclerosis and hypoxia which was suggested to have an important role in this process by the way of increased oxidative stress. In the present study, we aimed to evaluate the effects of nocturnal hypoxia pattern (intermittent versus sustained) on serum lipid peroxidation and paraoxonase (PON) activity. METHODS: Blood collections were performed in 44 OSA, 11 non-apneic, nocturnal desaturated COPD, and 14 simple snorer patients after full-night polysomnographic recordings. Nocturnal sleep and respiratory parameters, oxygen desaturation indexes, serum malondialdehyde (MDA) levels by measuring with the help of the formation of thiobarbituric acid reactive substances (TBARS), and PON activity were assessed in all subjects. RESULTS: OSA and COPD patients showed nocturnal hypoxemia, with a minimum oxygen saturation (SaO(2)) in ranges of 53-92 % and 50-87 %, respectively. The mean levels of TBARS was 15.7 ± 3.6 nmol and 15.3 ± 3.4 nmol malondialdehyde (MDA)/ml in OSA and COPD patients, respectively, while the mean level of the control group was 4.1 ± 1.2 nmol MDA/ml. The mean PON activity was found to be 124.2 ± 35.5 U/l in OSA patients and 124.6 ± 28.4 U/l in COPD patients. The mean PON activity of the control group was 269.0 ± 135.8 U/l. The increase in TBARS levels and the decrease in PON1 levels were statistically significant in both OSA and COPD patients according to controls (p < 0.001 for TBARS as well as PON1). CONCLUSION: The results of this study revealed that both OSA and non-apneic, nocturnal desaturated COPD patients showed increased levels of lipid peroxidation and decreased PON activity despite the differences in nocturnal hypoxia pattern.

Detection of reactive oxygen metabolites in malignant and adjacent normal tissues of patients with lung cancer.

BACKGROUND: Different types of reactive oxygen metabolites (ROMs) are known to be involved in carcinogenesis. Several studies have emphasized the formation of ROMs in ischemic tissues and in cases of inflammation. The increased amounts of ROMs in tumor tissues can either be because of their causative effects or because they are produced by the tumor itself. Our study aimed to investigate and compare the levels of ROMs in tumor tissue and adjacent lung parenchyma obtained from patients with lung cancer. METHODS: Fifteen patients (all male, mean age 63.6 ± 9 years) with non-small cell lung cancer were enrolled in the study. All patients were smokers. Of the patients with lung cancer, twelve had epidermoid carcinoma and three had adenocarcinoma. During anatomical resection of the lung, tumor tissue and macroscopically adjacent healthy lung parenchyma (control) that was 5 cm away from the tumor were obtained. The tissues were freshly frozen and stored at -20°C. The generation of ROMs was monitored using luminol- and lucigenin-enhanced chemiluminescence (CL) techniques. RESULTS: Both luminol (specific for (.)OH, H(2)O(2), and HOCl(-)) and lucigenin (selective for O(2)(.)(-)) CL measurements were significantly higher in tumor tissues than in control tissues (P <0.001). Luminol and lucigenin CL measurements were 1.93 ± 0.71 and 2.5 ± 0.84 times brighter, respectively, in tumor tissues than in the adjacent parenchyma (P = 0.07). CONCLUSION: In patients with lung cancer, all ROM levels were increased in tumor tissues when compared with the adjacent lung tissue. Because the increase in lucigenin concentration, which is due to tissue ischemia, is higher than the increase in luminol, which is directly related to the presence and severity of inflammation, ischemia may be more important than inflammation for tumor development in patients with lung cancer.

Antioxidant and neuroprotective effects of dexpanthenol in rats induced with traumatic brain injury.

Trauma-induced primary damage is followed by secondary damage, exacerbating traumatic brain injury (TBI). Dexpanthenol has been shown to protect tissues against oxidative damage in various inflammation models. This study aimed to investigate possible antioxidant and neuroprotective effects of dexpanthenol in TBI. Wistar albino male rats were randomly assigned to control (n = 16), trauma (n = 16) and dexpanthenol (500 mg/kg; n = 14) groups. TBI was induced under anesthesia by dropping a 300 g weight from 70-cm height onto the skulls of the rats. Twenty-four hours after the trauma, the rats were decapitated and myeloperoxidase (MPO) levels, luminol- and lucigenin-enhanced chemiluminescence (CL), malondialdehyde (MDA) levels, superoxide dismutase (SOD) levels, and catalase (CAT) and caspase-3 activities were measured in brain tissues. Following transcardiac paraformaldehyde perfusion, histopathological damage was graded on hematoxylin-eosin-stained brain tissues. In the trauma group, MPO level, caspase-3 activity and luminol-lucigenin CL levels were elevated (p < 0.05-0.001) when compared to controls; meanwhile in the dexpanthenol group these increases were not seen (p < 0.05-0.001) and MDA levels were decreased (p < 0.05). Decreased SOD and CAT activities (p < 0.01) in the vehicle-treated TBI group were increased above control levels in the dexpanthenol group (p < 0.05-0.001). in the dexpanthenol group there was relatively less neuronal damage observed microscopically in the cortices after TBI. Dexpanthenol reduced oxidative damage, suppressed apoptosis by stimulating antioxidant systems and alleviated brain damage caused by TBI. Further experimental and clinical investigations are needed to confirm that dexpanthenol can be administered in the early stages of TBI.