Evaluation of the protective effect of coenzyme Q10 against x-ray irradiation-induced ovarian injury.

AIM: This study focused on the anti-oxidant and anti-apoptotic effects of CoQ10 in ovaries exposed to pelvic radiation. METHODS: Thirty-two female rats were randomly assigned into four groups. Group I (control group), Group II: Only 2 Gy pelvic x-ray irradiation (IR) was administered as a single fractioned dose. Group III: 30 mg/kg CoQ10 was administered by oral gavage +2 Gy pelvic IR. Group IV: 150 mg/kg CoQ10 was administered by oral gavage +2 Gy pelvic IR. CoQ10 treatment was started 7 days before pelvic IR and completed 7 days later. The rats in Group III and IV were treated with CoQ10 for a total of 14 days. RESULTS: Histopathological analysis showed severe damage to the ovarian tissue in the radiation group, while both doses of CoQ10 showed normal histological structure. Likewise, while there was a high level of staining in the IR group for necrosis and apoptosis, the CoQ10 treated ones were like the control group. Tissue Malondialdehyde (MDA) levels were like the control group in the low-dose CoQ10 group, while the MDA levels of the high dose CoQ10 group were similar to the radiation group. CONCLUSION: Usage of low-dose CoQ10 has a radioprotective effect on radiation-induced ovarian damage. Although the use of high doses is morphologically radioprotective, no antioxidative effect was observed in the biochemical evaluation.

The effects of apelin-13 against cisplatin-induced nephrotoxicity in rats.

Acute kidney injury (AKI) is observed in nearly 60% of patients undergoing cisplatin (CP) therapy. The aim of this study was to reveal the potential effects of apelin-13 (AP-13) in the prevention of CP-induced renal toxicity, together with its antioxidant and anti-inflammatory effect mechanisms. Four experimental groups were established. Group 1, the control group, received 0.9% saline solution alone intraperitoneally (IP). Group 2, the CP group, received CP IP at 5 mg/kg once weekly for four weeks for induction of nephrotoxicity. In Group 3, the CP + Apelin-13 (AP-13) group, AP-13 was prepared at 20 nmol kg/d in sterile pyrogen-free saline before injection every day for four weeks and administered IP. CP was administered IP at 5 mg/kg once weekly for four weeks for induction of nephrotoxicity. In Group 4, the AP-13 group, AP-13 was prepared at 20 nmol kg/d in sterile pyrogen-free 0.9% saline before injection every day for four weeks and administered IP. Thiobarbituric acid reactive substances (TBARS), thiol (-SH), interleukin-1 beta, cleaved caspase-3, 8-hydroxy 2-deoxyguanosine (8-OHdG), and nuclear factor kappa B (NF-κß/p65) levels were then measured. Increased oxidative stress, inflammation, and apoptosis as a result of CP application activated the cascade. However, AP-13 administration reduced the oxidative stress increased by CIS with the determined antioxidant effect and reduced the damage by increasing total -SH levels. 8-OHdG and NF-κß/p65, which were up-regulated by triggering oxidative stress and inflammation, were down-regulated through the antioxidant and anti-inflammatory effects of AP-13.

The protective effects of trimetazidine against ovary ischemia-reperfusion injury via the TLR4/Nf-kB signal pathway.

Late diagnosis and treatment of ovarian ischemia can lead to worsening of ischemia, irreversible damage to ovarian functions and infertility. In this process, there is no approved medical treatment that can reduce the negative effects of ischemia and contribute positively to ovarian functions during reperfusion after detorsion. Rats were randomly assigned into one of six groups of eight animals each. The groups were designed as follows: The control group, The ischemia(I) group, The Ischemia + Trimetazidine (I + TMZ) (20 mg/kg) group, and The ischemia-reperfusion group (I/R). The Ischemia-Reperfusion + Trimetazidine (I/R + TMZ) (20 mg/kg) group, and The Sham + Trimetazidine (Sham + TMZ) (20 mg/kg) group. In this study performed thiobarbituric acid reactive substances (TBARS), total thiol (-SH), interleukin 1 beta (IL-1ß), interleukin 6 (IL-6), toll-like receptor 4 (TLR4), and nuclear factor-kappa B(NF-κß). Increased oxidative stress and inflammation were as a result of ovarian I and I/R application. Trimetazidine (TMZ), was sufficient to reduce the oxidative stress and inflammation. TLR4 and NF-κß, which were upregulated by oxidative stress and inflammation, were regressed by TMZ. TMZ should be considered as a potential therapeutic agent in addition to surgery in the clinical treatment of ovarian torsion.

The cardioprotective effects of perindopril in a model of polymicrobial sepsis: The role of radical oxygen species and the inflammation pathway.

Mortality rates associated with myocardial dysfunction due to sepsis and septic shock are generally high across the world. The present study focused on the antioxidant and anti-inflammatory effects of perindopril (PER) for the purpose of preventing the adverse effects of sepsis on the myocardium and developing new alternatives in treatment. The control group received only saline solution via the oral route for 4 days. The second group underwent cecal ligation puncture (CLP), and the third underwent CLP and received PER (2 mg/kg). Rats in the third group received 2 mg/kg PER per oral (p.o.) from 4 days before induction of sepsis. Thiobarbituric acid reactive species (TBARS), total thiol (-SH), interleukin-1 beta (IL-1ß), IL-6, 8-hydroxy-2'-deoxyguanosine (8-OHdG), and nuclear factor kappa B (NF-κB/p65) levels increased in the CLP groups. In contrast, PER (2 mg/kg) decreased the levels of biochemical parameters other than total-SH and decreased 8-OHdG, NF-κB/p65 immunopositivity in rat heart tissues. The data from this study show that impairment of the oxidant/antioxidant balance and inflammatory cytokine levels in favor of inflammation in heart tissue under septic conditions results in severe tissue damage. PER administration before sepsis was shown to exhibit antioxidant and anti-inflammatory properties by reducing these effects. This in turn increased the importance of PER as new evidence of its protective effects in heart tissue.

Effects of gadodiamide and gadoteric acid on lung tissue: A comparative study.

We set out to investigate the effects of gadodiamide and gadoteric acid, used for magnetic resonance imaging, on the lungs. In this study, 32 male Sprague Dawley rats were used. These were allocated into four groups; The first group (control) was untreated. The second group received isotonic saline on the first and fourth days of the week for 5 weeks. Following the same schedule, the third and fourth groups received a total of 2 mg/kg gadodiamide and gadoteric acid, respectively, in place of saline. The alveolar Wall thickness was evaluated. Gadodiamide and gadoteric acid significantly increased the numbers of collagen-3 and caspase-3 positive cells in the lung tissue (p < 0.05). In addition, these two substances increased the alveolar Wall thickness (p < 0.05). Furthermore, they increased the levels of malondialdehyde and glutathione (p < 0.05). This study demonstrates that both linear and macrocyclic contrast agents are toxic for the lungs in rats.

The effects of amiodarone in ovarian injury due to oxidative stress and inflammation caused by ischemia-reperfusion.

OBJECTIVE: Ovarian ischemia constitutes 2-3% of all gynecological emergencies. New-generation therapeutic agents need to be discovered, in addition to invasive interventions capable of reducing the risk of potential ovarian ischemia to a minimum and protecting against potential adverse outcomes. AIMS: To investigate the effects of amiodarone (AMD) on ischemia-reperfusion-induced oxidative stress and inflammation-induced ovarian damage. METHODS: The control group, received intraperitoneal (i.p.) injection of saline solution. The ischemia group (I-Group), was subjected to ischemia-induced injury without drug administration. The ischemia + AMD (50 mg/kg) group was subjected to ischemia injury and also received i.p. 50 mg/kg AMD prior to induction of ovarian ischemia. The ischemia-reperfusion (I/R group) was exposed to ischemia and reperfusion-induced injury without drug administration. The I/R + AMD (50 mg/kg) group underwent I/R injury together with i.p. administration of 50 mg/kg AMD prior to induction of ovarian I/R. The Sham + AMD group received intraperitoneal (i.p.) injection of 50 mg/kg AMD alone. In this study performed thiobarbituric acid reactive substances (TBARS), thiol (-SH), interleukin 1 Beta (IL-1ß), interleukin 6 (IL-6), toll-like receptor 4 (TLR4) and nuclear factor-kappa B(NF-κß). RESULTS: Increased oxidative stress and inflammation as a result of ovarian I and I/R application activated the cascade. AMD was not sufficient to reduce the oxidative stress and inflammation. TLR4 and NF-kß, which were up-regulated by triggering oxidative stress and inflammation, were not regressed by the effects of AMD. CONCLUSIONS: AMD, used as an antiarrhythmic agent, was found to be insufficient, despite its antioxidant and anti-inflammatory properties, to reduce the experimentally induced ovarian tissue damage.

Protective effects of nebivolol on ovarian ischemia-reperfusion injury in rat.

AIM: Ovarian torsion is a common gynecological emergency of reproductive ages, occurring at rates of 2.7-7.4%. This study aimed to evaluate the antioxidant effects of Nebivolol (NEB) and histopathological changes in experimental ischemic (I) and ischemic-reperfusion (I/R) injury in rat ovaries. METHODS: Forty-eight adult female rats were randomly separated into six groups as group 1 (control) receiving an oral saline solution for 3 days; group 2 (I) that underwent ischemia for 3 h with the application of atraumatic vascular clips; group 3 (I/R); group 4 (I + NEB) receiving 10 mg/kg NEB by oral gavage 30 min prior to the ischemia induction; group 5 (I/R + NEB) receiving 10 mg/kg NEB, and group 6 (control + NEB) receiving oral 10 mg/kg NEB for 3 days before ischemia induction followed by consequent reperfusion. Ovarian tissue damage was scored by histopathological analysis. Ovarian tissue malondialdehyde (MDA) and glutathione (GSH) levels were measured biochemically. RESULTS: The levels of MDA and tumor necrosis factor-alpha (TNF-α), and TUNEL assay positivity scores increased in the I and I/R groups. GSH levels decreased in all case groups (P < 0.05). The oral administration of NEB (10 mg/kg) to the I- and I/R-groups reduced the levels of MDA and TNF-α and TUNEL assay immunopositivity scores (P < 0.05). GSH levels increased in the treatment groups. CONCLUSION: The current experimental ovarian torsion study suggests a protective role for NEB against I and I/R injury in rat ovaries. NEB may be a novel agent for decreasing ovarian I/R injury.

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.

Can early myocardial infarction-related deaths be diagnosed using postmortem urotensin receptor expression levels?

PURPOSE: Myocardial infarction (MI) is one of the most prevalent causes of sudden adult death. It is difficult to diagnose early MI postmortem because there are no typical or characteristic changes in morphology. In this study, changes in the level of the mRNA for the urotensin receptor (UR) were investigated postmortem to determine the suitability of UR as a biomarker for diagnosis of early MI after death. METHODS: An MI rat model was developed by injecting rats with isoproterenol (ISO) (lethal dose 850 mg/kg) or normal saline (control group). The hearts of rats in the control and ISO-induced MI groups were harvested at 0, 1, 3, 6, 12, 24, 48, and 72 h (h) postmortem. The hearts were then immediately submerged in 1 mL of RNA stabilization solution and stored at 4 °C for <1 week before RNA extraction. Relative UR expression analysis was performed using the StepOne Plus Real Time PCR System with cDNA synthesized from rat heart. RESULTS: Postmortem UR mRNA expression was higher in the ISO-induced MI group than in the control group, at both 4 and 20 °C, at all of the time points examined except 72 h postmortem (p < 0.0001). The largest increases were observed at ambient temperature and 6 h postmortem. CONCLUSIONS: Based on our findings, increased postmortem UR expression could serve as a biomarker to aid diagnosis of early MI.

Long-term protective effects of lamotrigine in a rat ovarian ischemia-reperfusion model.

Ovarium torsion is a gynecological emergency that is common in women of reproductive age and requires early diagnosis and intervention. In this study, we aimed to investigate the long-term anatomical, histological and biochemical protective effects of lamotrigine in ovariums in the ischemia - reperfusion (I-R) model created experimentally in rats. A total of 40 female Sprague-Dawley rats, 14 weeks old, weighing 220-270 g were used in the study. The subjects were randomly distributed to form 4 groups named SHAM group, I - R group, I - R + Lamotrigine (LTG) group and R + LTG group. Under general anesthesia, the ovaries of the rats were reached and ischemia was created for 3 h with vascular clamps. 20 mg / kg LTG was administered intraperitoneally (ip.) to group 3 30 min before ischemia and to group 4 30 min before reperfusion. At the third hour of ischemia, the vascular clamps were opened and the abdomen of the rats was closed according to the surgical procedure. The rats were followed up for 28 days postoperatively and the ovarium tissues taken on the 28th day were examined anatomically and histologically. Biochemically, estradiol (E2), follicle stimulating hormone (FSH) and antimullerian hormone (AMH) levels were measured from blood samples taken from their hearts. Granulosa cells with diffuse vaculations were observed in degenerative follicles in group I-R. Again in this group, severe hemorrhage, fibrosis and edematous areas were observed in the ovarium stroma (Ovarian Histopathological Scoring (OHS): 7). In the I - R + LTG group, OHS was statistically significantly lower than the I - R group (OHS: 2; p < 0.000). In the R + LTG group, although the OHS score was calculated to be lower than the I - R group, there was no statistically significant difference (OHS: 6; p > 0.05). The protective effect of LTG against experimentally created ischemia and reperfusion damage was determined anatomically and histologically. No protective effect of LTG was observed in terms of FSH, E2 and AMH values measured from the blood sera of rats. These findings may provide a basis for future studies using LTG to treat ovarian ischemia-reperfusion injury.

The effect of the calcium channel blocker nimodipine on hippocampal BDNF/Ach levels in rats with experimental cognitive impairment.

OBJECTIVE: Alzheimer's disease (AD) occurs in approximately 10% to 30% of individuals aged 65 or older worldwide. Novel therapeutic agents therefore need to be discovered in addition to traditional medications. Nimodipine appears to possess the potential to reverse cognitive impairment-induced dysfunction in learning and memory through its regulatory effect on the brain-derived neurotrophic factor (BDNF), acetylcholine (Ach), and acetylcholinesterase (AChE) pathway in the hippocampus and prefrontal cortex. METHODS: Twenty-four male Sprague Dawley rats weighing 380 ± 10 g were used for behavioral and biochemical analyses. These were randomly and equally assigned into one of three groups. Group 1 received saline solution alone via the intraperitoneal (i.p) route, and Group 2 received 1 mg/kg/day i.p. scopolamine once a day for three weeks for induction of learning and memory impairments. In Group 3, 10 mg/kg/day nimodipine was prepared in tap water and administered orally every day for three weeks, followed after 30 min by 1 mg/kg/day scopolamine i.p. Behavior was evaluated using the Morris Water Maze test. BDNF, ACh, and AChE levels were determined using the ELISA test in line with the manufacturer's instructions. RESULTS: Nimodipine treatment significantly increased the time spent in the target quadrant and the number of entries into the target quadrant compared to the scopolamine group alone. Additionally, BDNF and ACh levels in the hippocampus and prefrontal cortex decreased following 20-day scopolamine administration, while AChE activation increased. CONCLUSION: Nimodipine exhibited potentially beneficial effects by ameliorating cognitive decline following scopolamine administration in the hippocampus and prefrontal cortex.

Agomelatine on cisplatin-induced nephrotoxicity via oxidative stress and apoptosis.

Drug-induced nephrotoxicity is the greatest deterrent to the use of cisplatin, which is a frequently used chemotherapeutic with proven effectiveness in cancer therapy. Agomelatine, which is used in the treatment of sleep disorders and depression, has gained attention in recent years with its antioxidative and anti-inflammatory effects. In this study, the effects of the synthetic melatonin agonist agomelatine on nephrotoxicity were investigated in a rat model of cisplatin-induced nephrotoxicity using biochemical, histological, and immunohistochemical methods. Thirty-two male rats were divided into 4 groups: 1. control group, 2. agomelatine group, 3. cisplatin group, 4. cisplatin + agomelatine group. In the cisplatin group, there were widespread atypical glomerular structures and vacuolization in tubular epithelial cells, necrotic tubules, deterioration of brush border structure in proximal tubules, and fibrotic areas characterized by diffuse polymorphonuclear leukocyte (PNL) and extensive collagen deposition in the interstitial spaces. However, in the cisplatin + agomelatine group, we observed a reduction in glomeruli of atypical structure and necrotic tubules, in PNL infiltration in interstitial spaces, and fibrotic areas compared to the cisplatin group. The cisplatin + agomelatine group showed lower malondialdehyde (MDA) serum creatinine, serum urea levels, and higher glutathione (GSH) levels compared to the cisplatin group. Immunohistochemical analyses revealed that the elevated NF-kß/p65, 8-OHdG, and cleaved caspase-3 positivity in the cisplatin group had significantly decreased in the cisplatin + agomelatine group. In conclusion, agomelatine showed a nephroprotective effect against cisplatin-induced nephrotoxicity.

Agomelatine attenuates cisplatin-induced cognitive impairment via modulation of BDNF/TrkB signaling in rat hippocampus.

Cisplatin is a drug used effectively in the treatment of malignant tumors. However, cisplatin has many side effects, including cognitive impairment. Agomelatine, a synthetic melatonin analogue, is an important antidepressant. Increasing evidence has shown that agomelatine may be a potential neuroprotective agent. The aim of this study was to investigate the effect of agomelatine on learning and memory functions in cisplatin-induced cognitive impairment in a rat model. Male rats were administered agomelatine and cisplatin for 4 weeks. Neurobehavioral tests were performed at the end of the 4th week. After behavioral tests, rats were euthanized and BDNF, TNF, IL-1ß, MDA and GSH levels were measured in hippocampal homegenates by ELISA. In addition, nNOS and TrkB receptor activity were measured immunohistochemically. The results showed that agomelatine significantly improved cognitive functions in spatial memory tests in rats with cisplatin-induced cognitive impairment. In addition, agomelatine treatment positively affected the discrimination index (DI). On the other hand, agomelatine treatment elevated cisplatin-suppressed hippocampal BDNF levels. Agomelatine treatment reduced cisplatin-induced neuroinflammation by suppressing TNF and IL-1ß levels. Similarly, agomelatine reduced oxidative stress in the hippocampus. Histological findings showed that agomelatine treatment reduced pyramidal neuron damage in hippocampal DG, CA1 and CA3. Cisplatin increased nNOS and TrkB positivity in DG, CA1 and CA3 neurons compared to control. In contrast, agomelatine treatment decreased both nNOS and TrkB positive scores. These findings indicate that agomelatine reduces cisplatin-related cognitive impairment by exerting anti-inflammatory action and possibly by the modulation of the BDNF/TrkB/nNOS pathways in the hippocampus.

The effects of vitamin B12 on the TLR-4/NF-κB signaling pathway in ovarian ischemia-reperfusion injury-related inflammation.

Ovarian ischemia is a gynecological emergency case that occurs as a result of ovarian torsion. Oxidative stress and inflammation play central roles in the development of ischemia/reperfusion injuries. We investigated the effects of Vitamin B12, thought to possess antioxidant characteristics on oxidative stress and the toll-like receptor 4 (TLR-4)/nuclear factorkappa B (NF-κB) signaling pathway in the ovaries during ischemia-reperfusion. Forty-eight rats were randomly assigned into six groups and the groups are designed as follows: Control (C), Ischemia (I), Ischemia + Vitamin B12 (I + B12), Ischemia-Reperfusion (I/R), I/R + Vitamin B12 (I/R + B12) and Sham + Vitamin B12. Vitamin B12 was administered at a dose of 400 mcg/kg via the i.p. route once daily for three days before I/R procedure. Tissue interleukin-1ß (IL-1ß) and interleukin-6 (IL-6) and malondialdehyde (MDA) levels in ovarian tissue increased following I/R, while glutathione (GSH) levels decreased. Moreover, extensive congestion, edema, hemorrhage and defective follicle were observed. Both NF-κB and TLR-4 expression levels also increased in the group exposed to I/R. While GSH levels increased, IL-1ß, IL-6, MDA, NF-κB and TLR-4 levels decreased with Vitamin B12 treatment. In addition, ovarian tissue without edema, mild congestion, and normal-appearing follicles were observed following Vitamin B12 administration. The findings showed that I/R in ovarian tissue resulted in significant tissue damage by increasing oxidative stress and inflammation. However, Vitamin B12 application was effective and alternative agent in reducing injury deriving from inflammation and oxidative stress developing in association with I/R in ovarian tissue.

Bee pollen increases hippocampal brain-derived neurotrophic factor and suppresses neuroinflammation in adult rats with chronic immobilization stress.

Chronic stress is a potential problem associated with anxiety, depression, and cognitive dysfunction. Bee pollen, a powerful antioxidant, has many therapeutic effects. In this study, we aimed to examine the effects of one of the Anatolian bee pollens on depression/anxiety. 24 male Sprague Dawley rats were divided into 3 groups as control, stress, and bee pollen + stress. Bee pollen (200 mg/kg/day) was given to rats exposed to physical stress for 10 days. Open field test (OFT) and forced swimming test (FST) were applied to monitor the behavioral changes of the rats. After behavioral tests, the rats were euthanized. Brain-derived neurotrophic factor (BDNF), interleukin 1 beta (IL-1ß), and tumor necrosis factor-alpha (TNF-α) levels were measured by ELISA to evaluate neurological and biochemical changes in rat hippocampal tissue. In addition, malondialdehyde (MDA) and glutathione (GSH) levels in the brain were evaluated. According to the behavioral test results, bee pollen reduced anxiety-like behavior but did not affect depression-like behavior. We also found that bee pollen suppressed neuroinflammation while reducing oxidative stress and lipid peroxidation in hippocampal tissues. Moreover, bee pollen significantly increased the level of BDNF in the hippocampus. In conclusion, bee pollen reduced oxidative damage and neuroinflammation caused by immobilization stress in rat brain tissue. Therefore, we suggest that bee pollen may be an effective natural compound in alleviating the negative effects caused by immobilization stress.

Comparison of linear versus macrocyclic gadolinium chelates in rat skeletal muscle.

OBJECTIVE: We investigated the effects on skeletal muscle of gadolinium based linear and macrocyclic radiocontrast agents applied at experimental intervals using histopathological methods. METHODS: Thirty-two male Sprague-Dawley rats were included in the study for histopathological analysis. No procedure was performed on the healthy control group. The sham group received 0.1 ml/kg intravenous (IV) saline solution through the tail vein 4 times weekly for 5 weeks. The gadodiamide group received total 2 mmol/kg IV gadodiamide through the tail vein 4 times weekly for 5 weeks. The gadoteric-acid group received 2 mmol/kg IV gadoteric acid through the tail vein 4 times weekly for 5 weeks. RESULTS: We determined no marked apoptotic myofibrils associated withcaspase-3 expression in these two groups. Furthermore, no calcineurin expression was observed in myofibrils in the two groups. However, quantitative analyses revealed a decrease in muscle-fiber area in the gadodiamide and gadoteric-acid groups compared to the control group (Respectively; p=0.001 and p=0.017). CONCLUSION: In our experimental study, linear and macrocyclic GBCAs applied at repeated doses played no role in myofibril damage induced by caspase-3 and calcineurin - nuclear factor of activated T-cells in skeletal muscle tissue.

The protective role of fosfomycin in lung injury due to oxidative stress and inflammation caused by sepsis.

AIM: Early and prompt treatment of sepsis by effective antibiotics against susceptible organisms may be lifesaving. However, increased antibiotic resistance and side effects of chemotherapeutic agents limiting their tolerability result in a restricted use of medications. This has led to an increased search for solution oriented novel treatments and therapeutic targets, as well as investigations on the pathogenesis and physiology of sepsis. In this study, we aimed to examine the antioxidant and anti-inflammatory effects of fosfomycin in sepsis resulting from other causes. MAIN METHODS: Sprague Dawley rats were assigned into three groups. Randomly selected control rats received intraperitoneal saline solution only. Only caecal puncture and ligation were carried out in the caecal ligation and puncture (CLP) group, while in the CLP + fosfomycin group (CLP + FOS), together with sepsis due to caecal puncture and ligation, 500 mg/kg of FOS was administered intraperitoneally (i.p.). KEY FINDINGS: As compared to the control group, elevated TBARS and TNF-α levels as well as increased expression of NF-kB/p65 and TLR-4 and reduced -SH levels were found in the lung tissue of CLP rats. On the other hand, TBARS and TNF-α levels were reduced and NF-kB/p65 and TLR-4 expressions were decreased together with increase in total -SH levels among CLP + FOS (500 mg/kg i.p.) rats. SIGNIFICANCE: FOS treatment may represent a promising agent in terms of reducing the sepsis-related lung injury due to its antimicrobial effects as well as its antioxidant and anti-inflammatory properties.

Apelin-13 activates the hippocampal BDNF/TrkB signaling pathway and suppresses neuroinflammation in male rats with cisplatin-induced cognitive dysfunction.

It has been established that cisplatin causes neuronal damage and cognitive impairment. However, the mechanism is not sufficiently clear. Apelin-13 is an endogenous peptide with strong neuroprotective effects through the synthesis of neurotrophic factors and suppression of inflammation. The aim of this study was to investigate the role of brain-derived neurotrophic factor/tropomyosin receptor kinase B (BDNF/TrkB) signaling pathway and the potential inhibitory effects of apelin-13 in the mechanism of cisplatin-induced hippocampal damage and cognitive impairment. Apelin-13 was administered to adult sprague dawley male rats at a dose of 20 nmol/kg every day for 4 weeks, cisplatin was administered at a dose of 5 mg/kg once a week for 4 weeks. The spatial and recognition memory tests of the rats were performed on the 5th week. BDNF and the inflammatory cytokines tumor necrosis factor-α (TNF-α) and interleukin-1ß (IL-1ß) levels were measured by ELISA in hippocampal homogenates. Pyramidal neuron and glial cell damage in the hippocampal CA1, CA3 and dentate gyrus (DG) were analyzed histologically. TrkB activity in the hippocampus was determined by immunohistochemical methods. Cisplatin impaired spatial and recognition memory in rats, while apelin-13 improved spatial memory but did not affect recognition memory. Cisplatin suppressed BDNF in the hippocampus while increased IL-1ß and TNF-α. In contrast, apelin-13 administration increased BDNF but significantly suppressed TNF-α and IL-1B. Cisplatin caused pyramidal neuron and glial cell damage in CA1, CA3 and DG. In the cisplatin + apelin-13 group, however, pyramidal neuron and glial cell damage was less than those without apelin-13. Cisplatin increased TrkB activity in the hippocampus, which was counteracted by apelin-13. In conclusion, apelin-13 reduced the cisplatin-induced cognitive deficiency, by suppressing inflammation and stimulating the synthesis and activation of neurotrophic factors in hippocampal tissue.

Can Dexmedetomidine Be Effective in the Protection of Radiotherapy-Induced Brain Damage in the Rat?

Approximately 7 million people are reported to be undergoing radiotherapy (RT) at any one time in the world. However, it is still not possible to prevent damage to secondary organs that are off-target. This study, therefore, investigated the potential adverse effects of RT on the brain, using cognitive, histopathological, and biochemical methods, and the counteractive effect of the α2-adrenergic receptor agonist dexmedetomidine. Thirty-two male Sprague Dawley rats aged 5-6 months were randomly allocated into four groups: untreated control, and RT, RT + dexmedetomidine-100, and RT + dexmedetomidine-200-treated groups. The passive avoidance test was applied to all groups. The RT groups received total body X-ray irradiation as a single dose of 8 Gy. The rats were sacrificed 24 h after X-ray irradiation, and following the application of the passive avoidance test. The brain tissues were subjected to histological and biochemical evaluation. No statistically significant difference was found between the control and RT groups in terms of passive avoidance outcomes and 8-hydroxy-2'- deoxyguanosine (8-OHdG) positivity. In contrast, a significant increase in tissue MDA and GSH levels and positivity for TUNEL, TNF-α, and nNOS was observed between the control and the irradiation groups (p < 0.05). A significant decrease in these values was observed in the groups receiving dexmedetomidine. Compared with the control group, gradual elevation was determined in GSH levels in the RT group, followed by the RT + dexmedetomidine-100 and RT + dexmedetomidine-200 groups. Dexmedetomidine may be beneficial in countering the adverse effects of RT in the cerebral and hippocampal regions.

The protective effects of angiotensin-converting enzyme inhibitor against cecal ligation and puncture-induced sepsis via oxidative stress and inflammation.

AIMS: Sepsis is a severe public health problem affecting millions of individuals, with global mortality rates caused by lower respiratory tract infections are approximately 2.38 million people a year die from respiratory failure caused by infection. Although ACE is known to contribute to damage in septicemia, the pathophysiological mechanisms of sepsis remain unclear. While mortality can be significantly reduced through effective and sensitive antibiotic therapy, antibiotic resistance restricts the use of these drugs, and the investigation of novel agents and targets is therefore essential. Our aim was to determine whether Perindopril (PER) has anti-inflammatory and antioxidant capable of preventing these adverse conditions resulting in injury in previous studies. MAIN METHODS: Sprague Dawley rats were randomly assigned into the control group, received oral saline solution alone for four days. the cecal ligation and puncture (CLP) group, underwent only cecal ligation and puncture induced sepsis, while the CLP + PER (2 mg/kg) underwent cecal ligation and puncture-induced sepsis together with oral administration of 2 mg/kg PER for four days before induction of sepsis. KEY FINDINGS: Malondialdehyde (MDA), tumor necrosis factor-alpha (TNF-α), Caspase-3 and nuclear factor kappa B (NF-kß/p65) levels increased in the CLP group. On the other hand, PER (2 mg/kg) oral administration to septic rats decreased MDA, TNF-α and increase glutathione (GSH) in the lung tissue. In addition, PER administration also decreased the lung tissue NF-κB and Caspase-3 immunopositivity against sepsis. SIGNIFICANCE: PER treatment may represent a promising means of preventing sepsis-induced lung injury via antioxidant and anti-inflammation effects.