Prophylactic Effect and Antiulcerogenic Potential of Probiotic Lactiplantibacillus plantarum E1K2R2 and its Exopolysaccharide Against Ibuprofen-Induced Acute Gastric Ulcer.

Lactiplantibacillus plantarum (Lpb. plantarum), as a safe probiotic microorganism, has been documented for its production of multiple bioactive compounds, such as exopolysaccharides (EPS), which have been used in the treatment of many gastrointestinal diseases, including gastric ulcers. The present study aims to investigate the prophylactic and antiulcerogenic effects of the potential probiotic Lbp. plantarum E1K2R2 and its EPS against ibuprofen-induced gastric ulcer. A gastric ulcer model was established by feeding fasted rats with ibuprofen at a single dose (200 mg/kg body weight). The Lpb. plantarum E1K2R2 (109 CFU), its EPS (200 mg/kg bw), and the anti-ulcer reference drug (omeprazole) (20 mg/kg bw) were separately used to feed rats for seven consecutive days before ibuprofen administration. The mechanisms were meticulously examined, focusing on the anti-secretory activity and mucus production as well as the anti-inflammatory and antioxidant activities. The findings revealed that the gastro-preventive effect of Lbp. plantarum E1K2R2 (88.43%) was higher than that of the EPS (66.26%) and close to that of omeprazole (89.87%). This effect was achieved through similar mechanisms, including regulation of the secretory activity, augmentation of mucus production, mitigation of inflammation, and enhancement of the gastric mucosa's antioxidant capacity. Moreover, it was found that Lbp. plantarum E1K2R2 and its EPS induce the activities of gastric antioxidant enzymes: superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), and S-transferase (GST); enhance glutathione (GSH) content; and reduce mucosal nitric oxide (NO), myeloperoxidase (MPO), and malondialdehyde (MDA) levels. Furthermore, histopathological and hematological examinations confirmed that both pre-treatments could effectively maintain the structural integrity of the gastric mucosa and improve some hematological parameters, respectively. This implies that Lpb. plantarum E1K2R2 and its EPS possess the potential to counteract ibuprofen-associated gastric ulcers, leveraging a variety of protective mechanisms.

Gastroprotective effect of vanillic acid against ethanol-induced gastric injury in rats: involvement of the NF-κB signalling and anti-apoptosis role.

BACKGROUND: Vanillic acid (VA; 4-hydroxy-3-methoxybenzoic acid) is a flavouring agent found in various natural sources such as olives, fruits, and green tea. While VA exhibits numerous pharmacological effects, its potential protective effects against gastric injury warrants further investigation. Therefore, the primary objective of this study is to elucidate investigate the gastroprotective properties of VA against ethanol-induced gastric injury. METHODS AND RESULTS: Rats were orally administered either saline or VA at different doses (50, 100, and 200 mg/kg/day), with omeprazole (20 mg/kg) serving as a positive control, for fourteen consecutive days before ethanol administration. Blood and gastric tissue samples were collected one hour after ethanol administration for biochemical, molecular, and histological analyses. Pre-treatment with VA before ulcer induction alleviated both macroscopic and microscopic damage. It also increased antioxidant glutathione levels and decreased malondialdehyde and myeloperoxidase activity, along with reducing inflammatory markers such as tumour necrosis factor (TNF)-α, interleukin (IL)-6, and nuclear factor kappa B (NF-κB). Additionally, VA pre-treatment reversed the elevation of Bax mRNA expression and gastric caspase-3 levels induced by gastric damage. It also mitigated the reduction in Bcl-2 mRNA expression. CONCLUSION: These findings suggest that VA exerts protective effects against ethanol-induced gastric injury in rats. It achieves this by augmenting gastric antioxidant capacity and mitigating oxidative, inflammatory, and apoptotic damage.

Histological and biochemical effects of an ethanolic extract of Myrtus communis leaf on the pancreases of rats fed high fat diets.

We investigated the effects of an ethanolic extract of Myrtus communis subsp. communis (MC) leaves on the pancreases of rats fed with a high fat diet (HFD). Wistar albino rats were fed either with standard lab chow (Control group) or with a 45% fat diet (HFD and HFD+MC groups) for 4 months, with the MC extract (100 mg/kg) being administered by orogastric gavage to rats in the HFD+MC group during the last month. Blood and pancreas samples were collected from all experimental groups at the end of the study. Insulin and leptin levels, and the lipid profile, were analyzed in the blood serum. Pancreatic injury was assessed histologically. Insulin, nuclear factor kappa beta (NF-κB), and alpha-smooth muscle actin (α-SMA) were assessed using immunohistochemistry. Apoptosis was assessed using terminal deoxynucleotidyl transferase dUTP nick end-labeling (TUNEL) immunohistochemistry. In addition, oxidant/antioxidant activity was analyzed by biochemical methods. Increased body weight, serum insulin and leptin levels, blood glucose level and pancreatic tissue malondialdehyde (MDA), 8-hydroxy-2'-deoxyguanosine (8-OHdG) levels, myeloperoxidase (MPO) activity and decreased tissue glutathione (GSH) level were observed in the HFD group compared to the Control group, in addition to dyslipidemia. An increased histopathological damage score, pancreatic islet area, insulin, TUNEL, NF-κB and α-SMA immunoreactivity were seen in animals from the HFD group compared to the Control group. However, such pathological changes were reduced in the HFD+MC group. Our data indicate further investigation of MC extract as a therapeutic adjuvant for HFD-induced pancreatic injury, acting via anti-inflammatory and antioxidant mechanisms, is worth carrying out.

Ameliorative effects of Myrtus communis L. extract involving the inhibition of oxidative stress on high fat diet-induced testis damage in rats.

The possible protective effects of Myrtus communis L. (MC) extract on a high fat diet (HFD)-induced testicular injury in a rat model were investigated using histological and biochemical methods. Wistar albino rats were divided into three groups: a standard diet control group; a HFD group; and an HFD+MC group. The HFD and HFD+MC groups were fed with a HFD for 16 weeks. MC extract (100 mg/kg) was given orally five days a week to the rats in the HFD+MC group during the last four weeks of the experiment. Leptin, triglyceride, high-density lipoproteins, cholesterol, estrogen, testosterone, LH and FSH were analyzed in blood serum. Sperm parameters were evaluated from the epididymis. Testicular morphology, proliferative, apoptotic and NADPH oxidase-2 (NOX2)-positive cells were evaluated histologically. Testicular oxidative stress parameters were analyzed biochemically. In the HFD group, lipid and hormone profiles were changed, abnormal spermatozoa, degenerated seminiferous tubules with apoptotic and NOX2-positive cells were increased in number, and sperm motility and germinal proliferative cells decreased compared to the control group. Moreover, testicular malondialdehyde, 8-hydroxy-2-deoxyguanosine and myeloperoxidase levels increased, whereas glutathione and superoxide dismutase levels decreased in the HFD group compared to the control group. All these histological and biochemical features were ameliorated by MC treatment of HFD-fed rats. In conclusion, HFD caused alterations in sperm parameters and testicular morphology by increasing oxidative damage and apoptosis. MC extract may have potential protective effects by inhibiting oxidative damage.

Neuropeptide W facilitates chronic gastric ulcer healing by the regulation of cyclooxygenase and NF-κB signaling pathways.

AIMS: Putative beneficial effects of neuropeptide W (NPW) in the early phase of gastric ulcer healing process and the involvement of cyclooxygenase (COX) enzymes were investigated in an acetic acid-induced gastric ulcer model. MAIN METHODS: In anesthetized male Sprague-Dawley rats, acetic acid was applied surgically on the serosa and then a COX-inhibitor (COX-2-selective NS-398, COX-1-selective ketorolac, or non-selective indomethacin; 2 mg/kg/day, 3 mg/kg/day or 5 mg/kg/day; respectively) or saline was injected intraperitoneally. One h after ulcer induction, omeprazole (20 mg/kg/day), NPW (0.1 µg/kg/day) or saline was intraperitoneally administered. Injections of NPW, COX-inhibitors, omeprazole or saline were continued for the following 2 days until rats were decapitated at the end of the third day. KEY FINDINGS: NPW treatment depressed gastric prostaglandin (PG) I2 level, but not PGE2 level. Similar to omeprazole, NPW treatment significantly reduced gastric and serum tumor necrosis factor-alpha and interleukin-1 beta levels and depressed the upregulation of nuclear factor kappa B (NF-κB) and COX-2 expressions due to ulcer. In parallel with the histopathological findings, treatment with NPW suppressed ulcer-induced increases in myeloperoxidase activity and malondialdehyde level and replenished glutathione level. However, the inhibitory effect of NPW on myeloperoxidase activity and NPW-induced increase in glutathione were not observed in the presence of COX-1 inhibitor ketorolac or the non-selective COX-inhibitor indomethacin. SIGNIFICANCE: In conclusion, NPW facilitated the healing of gastric injury in rats via the inhibition of pro-inflammatory cytokine production, oxidative stress and neutrophil infiltration as well as the downregulation of COX-2 protein and NF-κB gene expressions.

Neuropeptide W Exhibits Preventive and Therapeutic Effects on Acetic Acid-Induced Colitis via Modulation of the Cyclooxygenase Enzyme System.

BACKGROUND: The novel peptide neuropeptide W (NPW) was originally shown to function in the control of feeding behavior and energy homeostasis. The aim of this study was to elucidate the putative preventive and therapeutic effects of NPW on colitis-associated oxidative injury and the underlying mechanisms for its action. METHODS: Sprague-Dawley rats in the acute colitis groups received NPW (0.5, 1 or 5 µg/kg/day) injections prior to induction of colitis with acetic acid, while the chronic colitis groups were treated after the induction of colitis. In both acute and chronic colitis (CC) groups, treatments were continued for 5 days and the rats were decapitated at the 24th hour of the last injections and colon tissues were collected for assessments. RESULTS: NPW pretreatment given for 5 days before colitis induction, as well as treating rats with NPW during the 5-day course of CC, abolished colonic lipid peroxidation. NPW treatment prevented colitis-induced reduction in blood flow, diminished neutrophil infiltration, and pro-inflammatory cytokine responses. NPW pretreatment only at the higher dose reduced colonic edema and microscopic score and preserved colonic glutathione stores. Elevations in cyclooxygenase (COX) enzyme activity and COX-1 protein level during the acute phase of colitis as well as reduction in COX-2 were all reversed with NPW pretreatment. In contrast, NPW treatment was effective in reducing the elevated COX-2 concentration during the chronic phase. CONCLUSIONS: NPW alleviates acetic acid-induced oxidative colonic injury in rats through the upregulation of colonic blood flow as well as the inhibition of COX-2 protein expression and pro-inflammatory cytokine production.

Hepatoprotective effects of parsley (Petroselinum Crispum) extract in rats with bile duct ligation.

BACKGROUND AND STUDY AIMS: This study aimed to investigate the possible protective effects of parsley extract (Petroselinum Crispum; PC) against oxidative liver damage caused by bile obstruction in rats. MATERIAL AND METHODS: Bile duct ligation (BDL) method was used to induce liver injury in rats. The rats were divided into the three groups each consisting of 8 rats; Sham-operated control (C), bile duct ligated + saline treated (BDL), and BDL + PC treated groups. PC extract was given at a dose of 2 g/kg orally for 28 days. Aspartate amino transferase (AST), alanin amino transferase (ALT), and bilirubin levels were analyzed in sera. In order to determine free radicals in liver injury, luminol and lucigenin chemiluminescence tests used. Oxidative stress was evaluated through superoxide dismutase, glutathione, malondialdehyde, Na+/K+-ATPase and 8-hydroxy guanosine levels. Furthermore, inflammation marker myeloperoxidase, apoptosis marker caspase-3, and fibrosis markers TGF- ß and hydoxyproline were investigated. The liver tissues were also examined for histological evaluations. RESULTS: While PC treatment decreased AST and ALT levels which increased with BDL, oxidant damage parameters also decreased with this treatment. CONCLUSION: The present study, which is the first research for PC extract on cholestasis induced liver damage, demonstrated that PC extract could be a potential therapeutic agent against liver fibrosis and need further studies.

Evaluation of toxic effects of dapagliflozin on reproductive system in diabetic rats.

BACKGROUND: Dapagliflozin (DAPA), sodium-glucose cotransporter 2 (SGLT2) inhibitor, is an insulin-independent antidiabetic drug used to control hyperglycaemia by promoting glucose excretion from the kidney. Its adverse effects include orthostatic hypotension, dehydration and urinary tract and genital infections caused by glycosuria. DAPA is subjected to constant additional monitoring, as drugrelated adverse reactions are frequently updated in line with the results of case studies, clinical trials and in vivo studies. Some antidiabetic drugs have shown potential harmful effects on the male reproductive system; however, the effects of DAPA have not been sufficiently studied in this capacity. Aiming to fill this gap in the literature, the present work investigates the toxic effects of DAPA on the male reproductive system. METHODS: Diabetes was induced using streptozotocin (STZ) in adult male Sprague-Dawley (SD) rats. DAPA (10 mg/kg) was administered by gavage to the diabetic rats over 28 days, after which the animals were sacrificed. The biochemical, morphological and histological examinations were performed on testicle, sperm and plasma samples. RESULTS: As a result of this study, we observed reproductive system damage in the form of induction of apoptosis in the seminiferous tubules, changes in testis and sperm parameters and oxidative damage, alongside the development of diabetes in test animals. With the exception of sperm morphological damage, the changes observed in diabetic animals treated with DAPA were similar to those of the control group. Improvements were observed in histological, hormonal and proliferative parameters in the DAPA group compared to the DC group. DISCUSSION: Even if DAPA is found to have antioxidant effects, it may raise abnormal sperm counts through a mechanism completely independent of these effects and thus may not have a significant toxic effect on the male reproductive system.

Exercise improves testicular morphology and oxidative stress parameters in rats with testicular damage induced by a high-fat diet.

Obesity and male infertility are problems that affect population. Exercise is a nonpharmacological way to reduce the negative health effects of obesity. The purpose of this study was to examine the effects of exercise on hormone levels, blood-testis barrier, and inflammatory and oxidative biomarkers in rats that became obese due to a high-fat diet (HFD). Male rats received a standard diet (STD group) or a HFD (HFD group) for 18 weeks. During the final 6 weeks of the experiment, swimming exercises (1 h/5 days/week) were given to half of these animals (STD + EXC and HFD + EXC groups). Finally, blood and testicular tissues were analysed by biochemical and histological methods. Body weight, leptin, malondialdehyde, interleukin-6, TNF-alpha and myeloperoxidase levels, apoptotic cells and DNA fragmentation were increased, and testis weight, insulin, FSH, LH, testosterone, glutathione and superoxide dysmutase levels, proliferative cells, ZO-1, occludin, and gap junction protein Cx43 immunoreactivity were decreased in the HFD group. All these hormonal, morphological, oxidative and inflammatory biomarkers were enhanced in the HFD + EXC group. It is thought that exercise protected testicular cytotoxicity by regulating hormonal and oxidant/antioxidant balances and testicular function, inhibiting inflammation and apoptosis, as well as preserving blood-testis barrier.

The Effect of Metformin on Ethanol- and IndomethacinInduced Gastric Ulcers in Rats.

BACKGROUND: Previous studies found metformin as an effective agent to suppress oxidative stress, inflammation, and apoptosis in various inflammatory diseases. The present study investigated the effect of metformin against 2 experimental gastric injury models in rats, using macroscopical, histopathological, biochemical, and immunostaining studies. METHODS: After 24 hours of fasting, male Sprague-Dawley rats (280-400 g) (n = 8 per group) received indomethacin (80 mg/kg; indo ulcer group) or absolute ethanol (5 mL/kg; ethanol ulcer group) or vehicle orally by gavage. Metformin (500 mg/kg) was given orally for 3 days prior to indomethacin or ethanol challenge. Ranitidine (50 mg/kg) was given orally for 3 days before indomethacin or ethanol administration as a positive control. On day 3, the animals were euthanized 6 hours after indo or 1 hour after ethanol challenge. Gastric samples were used for macroscopic scoring, histopathological examinations, and biochemical assays. Trunk blood was collected for the assessment of interleukin-1ß level. RESULTS: In both ethanol ulcer and indo ulcer groups, metformin decreased the extent of gastric lesions macroscopically and microscopically, improved the high chemiluminescence levels, and the percentage of terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL)-positive apoptotic cells compared with untreated ulcer groups. Gastric blood flow analysis revealed significant increases in both metformin-treated ulcer groups compared to untreated ulcer groups. CONCLUSION: The findings of the present work demonstrated the gastroprotective effect of metformin against the development of gastric mucosal lesions induced by ethanol and indomethacin in non-diabetic, normoglycemic rats via its antioxidant and anti-apoptotic properties and partly from its ability to restore blood flow.

Melatonin Alleviates Ovariectomy-Induced Cardiovascular Inflammation in Sedentary or Exercised Rats by Upregulating SIRT1.

We aimed to evaluate the impact of hormone replacement, melatonin, or exercise alone or their combination on oxidative damage and functional status of heart, brain, and aorta of ovariectomized (OVX) rats and to determine whether the signaling pathway is dependent on sirtuin-1 (SIRT1). Ovariectomized Sprague Dawley rats were orally given either a hormone replacement therapy (1 mg/kg/day,17ß estradiol; HRT) or melatonin (4 mg/kg/day) or HRT + melatonin treatments or tap water, while each group was further divided into sedentary and exercise (30 min/5 days/week) groups. After the heart rate measurements and memory tests were performed, trunk blood was collected at the end of the 10th week to determine metabolic parameters in serum samples. Tissue samples of abdominal aorta, heart, and brain were taken for biochemical measurements and histopathological evaluation. Heart rates and memory performances of the OVX rats were not changed significantly by none of the applications. Melatonin treatment or its co-administration with HRT upregulated the expressions of IL-10 and SIRT1, reduced the expressions of IL-6 and TNF-α, and reduced DNA damage in the hearts and thoracic aortae of non-exercised rats. Co-administration of melatonin and HRT to exercised OVX rats reduced inflammatory response and upregulated SIRT1 expression in the aortic and cardiac tissues. The present study suggests that melatonin treatment, either alone or in combination with exercise and/or HRT, upregulates SIRT1 expression and alleviates oxidative injury and inflammation in the hearts and aortas of OVX rats. Melatonin should be considered in alleviating cardiovascular disease risk in postmenopausal women.

Effects of in utero exposure to valproate or levetiracetam on the seizures and newborn histopathology of genetic absence epilepsy rats.

Valproate (VPA) and levetiracetam (LEV), the two broad spectrum antiseizure drugs with antiabsence effects were previously tested for their antiepileptogenic effects when administered in the early postnatal period and revealed possible modification of the epileptogenic process though the effect being not persistent. The aim of this study was to investigate the effects of in utero exposure to these drugs on the absence epilepsy seizures of Genetic Absence Epilepsy Rats from Strasbourg (GAERS) rats on electroencephalogram (EEG) which are characterised by bilateral, symmetrical, and synchronized spike-and-wave discharges (SWDs). Considering LEV was proposed as a safer drug of choice in pregnancy, its effects on the newborn histopathology of GAERS was also investigated. Adult female GAERS were randomly grouped as VPA-(400 mg/kg/day), LEV- (100 mg/kg/day), and saline-treated. The drugs were injected into the animals intraperitoneally starting before pregnancy until parturition. The lungs, kidneys, and brains of the LEV-exposed newborns were evaluated histologically to be compared with unexposed naïve Wistar and GAERS newborns. Rest of the VPA-, LEV-, and saline-exposed offsprings were taken for EEG recordings on postnatal day 90. VPA or LEV did not show significant effect on mean cumulative duration and mean number of SWDs on EEG. The lungs of the LEV-exposed offsprings showed thickened alveolar epithelium in most regions, suggesting incomplete development of the alveoli. The renal examination revealed dilated Bowman's spaces in some renal corpuscles, which may be interpreted as a deleterious effect of LEV on the kidney. In addition, brain examination of LEV- and saline-exposed groups revealed irregularities in cortical thickness compared to Wistar control group. Lack of significant difference on SWD parameters may indicate that the mechanism responsible for the antiepileptogenic effects of VPA and LEV may not be operating in the prenatal period. The detrimental effect of LEV exposure observed in our study on the lungs and the kidneys of the newborns should be investigated by further studies with advanced molecular and biochemical techniques.

Neuropeptide W Attenuates Oxidative Multi-Organ Injury in Rats Induced with Intra-Abdominal Sepsis.

Sepsis leads to systemic hypotension, disturbed perfusion, inflammation, and tissue toxicity in vital organs. Neuropeptide W (NPW) has modulatory effects in the control of blood pressure and inflammatory processes, implicating a potential beneficial effect against sepsis-induced oxidative damage. Under anesthesia, male Sprague Dawley rats underwent cecal ligation and puncture. Immediately after surgery, either saline or TNF-alpha inhibitor (etanercept; 1 mg/kg) antibiotic (ceftriaxon; 10 mg/kg) combination or NPW (0.1, 1, or 3 µg/kg) was given subcutaneously, and injections were repeated on the 12th and 24th h. The sham-operated control group was treated with saline at the same time points. All rats were euthanized on the 25th h of surgery. Sepsis resulted in oxidative damage of the brain, heart, lung, liver, and kidney. Elevations in blood urea nitrogen and alkaline phosphatase, showing renal and hepatic dysfunction, were not evident when septic rats were treated with NPW. NPW reduced serum levels of C-reactive protein, corticosterone, and interleukin-6, while histopathologically verified tissue damage in all the studied tissues was ameliorated. NPW treatment suppressed lipid peroxidation in the heart, lung, and brain, and the depleted antioxidant GSH levels of the brain and heart were replenished by NPW. Moreover, sepsis-related neutrophil recruitment to the liver and lung was also suppressed by NPW. Although the survival rate of the rats was not significantly prolonged by NPW, most of these improvements in systemic and local inflammatory events were comparable with those reached by the etanercept and antibiotic combination, suggesting the therapeutic impact of NPW during the acute period of sepsis.

High cholesterol diet activates ER stress mediated apoptosis in testes tissue: Role of α-tocopherol.

The seminiferous tubules where spermatogenesis occurs are enveloped and protected by the Sertoli cells to support germ cells undergoing meiosis to produce haploid gametes. Clearly, induction of apoptosis in seminiferous tubules leads to abnormalities in spermatogenesis and male infertility. Studies demonstrated that increased hyperlipidemia impairs male infertility and spermatogenesis by enhancing seminiferous tubules apoptosis. However, molecular mechanisms underlying high-cholesterol-mediated testicular damage remain poorly elucidated. In this scope, we established a rabbit model and investigated the role of endoplasmic reticulum (ER) stress on high cholesterol diet induced seminiferous tubule apoptosis. Histopatological examinations revealed increased seminifer tubule apoptosis in testes of rabbits fed high cholesterol diet. In addition, phosphorylated forms of IRE1 and PERK, two well-identified markers of ER stress, were significantly induced in accordance with high cholesterol diet. High cholesterol diet also exhibited CHOP induction in testes, indicating increased ER stress related apoptosis. Supplementation of α-tocopherol significantly attenuated cholesterol mediated ER stress, and restored seminiferous tubules apoptosis. Taken together, our findings suggest that α-tocopherol might be capable to reduce testicular damage via ameliorating histopatological features and inhibiting seminiferous tubules apoptosis in hypercholesterolemic rabbits.

Effects of Myrtus communis L. Extract and Apocynin on Lens Oxidative Damage and Boron Levels in Rats with a High Fat-Diet.

OBJECTIVES: Nutritional obesity causes oxidant damage in the body and cataract formation in the lenses by increasing the formation of free radicals. Myrtus communis leaf extracts (Myr) have antioxidant properties, and apocynin (Apo) is an effective NADPH-oxidase inhibitor. The data on tissue boron levels are quite lacking. The aim of this novel study was to investigate the effects of Myr and Apo treatment on boron levels and oxidative lens damage in rats fed a high-fat diet (HFD). MATERIALS AND METHODS: Wistar albino male rats were randomly divided into four groups: the control group, HFD group, HFD + Myr group, and HFD + Apo group. Body weight and blood lipids were determined before and after the experiment. After decapitating the rats, the lenses were removed and homogenized. Catalase (CAT) and superoxide dismutase (SOD) activities and boron, malondialdehyde (MDA), and reduced glutathione (GSH) levels in the lens homogenates were determined. RESULTS: The HFD increased serum triglyceride (p<0.05), total cholesterol level (p<0.001), body weight (p<0.001), and lens MDA levels (p<0.01) and decreased lens GSH (p<0.05) and boron level (p<0.01), SOD (p<0.001), and CAT activity (p<0.001). However, Myr and Apo treatment reduced the rats' body weight (p<0.001), serum triglyceride (p<0.05), and total cholesterol level (p<0.001) and increased lens boron (p<0.01; p<0.001), GSH levels (p<0.05; p<0.01), and CAT activity (p<0.001). CONCLUSION: Both Myr and Apo may be able to reduce oxidative stress in the lenses of obese rats caused by HFD by increasing boron levels.

Electromagnetic Waves from Mobile Phones may Affect Rat Brain During Development.

AIM: To investigate the effects of electromagnetic waves (EMWs) from mobile phones (MPs) on rat brains of rats by morphological and biochemical analysis. MATERIAL AND METHODS: EMW was applied for two hours/day until birth in stand-by fetal and EMW fetal groups and postnatal 60 < sup > th < /sup > day in stand-by and EMW groups. The control group was not exposed to MP. On postnatal 60 < sup > th < /sup > day, brain malondialdehyde (MDA) and glutathione (GSH) levels were measured, and western blot analysis was performed to determine glial fibrillary acidic protein (GFAP) content. Hematoxylin and eosin staining and GFAP immunohistochemistry were applied. Trigeminal nerves were examined using the transmission electron microscope. RESULTS: In comparison to controls, rats exposed to MP in stand-by or talk modes had significantly increased neuronal damage in the cortex and hippocampus. Increased MDA levels in the EMW group and decreased GSH levels in the stand-by, EMW fetal and EMW groups were found compared with controls. Increased GFAP content in the EMW group and increased GFAP staining in the EMW fetal and EMW groups compared to controls were observed. EMW group had a significantly decreased number of myelinated axons than control animals. CONCLUSION: The results of this study suggests that 1800 MHz EMWs (SAR=1.79 W/kg) exposure in the prenatal and early postnatal life may lead to trigeminal nerve damage in addition to oxidative stress-induced neuronal degeneration and astroglial activation in the rat brain. Effects seem to be mode related, being more detrimental in groups exposed to MP during talk mode.

Sleeve gastrectomy-induced endocrine changes in the remnant stomachs of premenopausal and postmenopausal rats: role of the estrogen receptors.

BACKGROUND: Although alterations in the plasma levels of leptin, glucagon-like peptide-1, and gastrin were linked with bariatric surgery outcomes, gastric production of these peptides was not elucidated before. OBJECTIVE: The aim was to evaluate the impact of estrogen depletion and estrogen receptors (ERs) on sleeve gastrectomy (SG)-induced alterations in gastric hormone production, gastric mucosal integrity, and bone mass. SETTING: Physiology Research Lab at the University. METHODS: Female Sprague-Dawley rats underwent ovariectomy or sham operation (control), and 2 months later SG or sham SG was performed. Rats received either nonselective agonist 17 ß, ER-α agonist, ER-ß agonist, or vehicle for 3 weeks. Trunk blood and gastric tissues were collected for biochemical measurements, while histopathologic examination was performed in gastric and femur samples. RESULTS: In the presence of intact ovaries, SG-induced weight loss was accompanied by reductions in the gastric synthesis of leptin and gastrin, while gastric glucagon-like peptide-1 was additionally decreased when SG was performed at the postmenopausal state. SG elevated the depleted serum estradiol levels of menopause, implicating a beneficial effect, but the occurrence of severe gastric mucosal injury was triggered. On the other hand, using ER agonists upregulated gastrin-expressing cells, ameliorated gastric injury, and improved bone loss. CONCLUSIONS: SG, either at premenopausal or postmenopausal state, resulted in considerable loss in bone mass, along with reductions in the gastric levels of gastrin and leptin. Functional status of the ovaries needs to be taken into consideration when monitoring the outcomes of SG, and ER agonists could be of value in controlling SG-induced complications.

Morphological evaluation of the effects of exercise on high-fat-diet-induced liver damage in rats.

BACKGROUND/AIMS: This study was aimed to investigate the protective effects of swimming exercise on nonalcoholic fatty liver disease (NAFLD) associated with high fat diet-induced obesity, using microscopical and biochemical parameters. MATERIALS AND METHODS: Sprague Dawley male rats were fed either standard chow (STD group; 6% fat) or high-fat diet (HFD group; 45% fat) for 18 weeks. Animals were divided into four groups, STD, STD + EXC, HFD, HFD + EXC. Exercise groups were submitted to swimming training 5 days of week and 1h of per day, during the last 6 weeks of the experiment. At the end of the experiment, liver samples were evaluated for morphologically and ultrastructurally. Moreover, malondialdehyde (MDA) and glutathione (GSH) levels were evaluated in liver samples. RESULTS: Normal morphology of liver parancyma with hepatocytes and sinusoids was observed in the STD and STD+EXC groups. Steatosis, lipid accumulation, ballooned hepatocytes, decrease of glycogen deposits and fibrosis in periportal area were observed in HFD group. Liver MDA level was increased and GSH level was decreased in HFD group. Exercise treatment ameliorated these morphological and oxidative changes in HFD induced liver damage. CONCLUSION: Based on morphological and biochemical analysis, we could conclude that swimming training ameliorated obesity-induced liver damage by regulating lipid accumulation and oxidative damage.

Ultrastructural investigation of synaptic alterations in the rat hippocampus after irradiation and hyperthermia.

This study aimed to investigate ultrastructural synaptic alterations in rat hippocampus after in utero exposure to irradiation (IR) and postnatal exposure to hyperthermia (HT). There were four groups in each of the time points (3rd and 6th months). IR group: Pregnant rats were exposed to radiation on the 17th gestational day. HT group: Hyperthermia was applied to the rat pups on the 10th day after their birth. IR+HT group: Both IR and HT were applied at the same time periods. Control group: No IR or HT was applied. Rat pups were sacrificed after 3 and 6 months. Thin sections from the dentate gyrus (DG) and the CA3 of hippocampus were evaluated for synapse numbers by electron microscopy. Synapses were counted, and statistical analysis was performed. Abnormalities in myelin sheath, mossy terminals and neuropil were observed in the CA3 and DG of all groups. The synapses in the CA3 region were significantly increased in the IR-3rd month, IR-6th month, and IR+HT-3rd month groups vs control group. Synapses were significantly increased in the DG of HT-3rd month group. A trend for an increase in synapse numbers was seen in the CA3 and DG. Increased number of synapses in the rat hippocampus may be due to mossy fiber sprouting, possibly caused by in utero irradiation and/or postnatal hyperthermia.

Estrogen receptor agonists protect against acetaminophen-induced hepatorenal toxicity in rats.

AIMS: Acetaminophen-induced hepatorenal toxicity varies among sexes with controversial results among species. The aim was to compare the impact of sex and ovarian hormones on hepatorenal toxicity and to elucidate protective effects of estrogen and estrogen receptor (ER) agonists. MAIN METHODS: Under anesthesia, female rats underwent ovariectomy (OVX) or sham-OVX. Starting at postsurgical 40th day, OVX-rats received subcutaneously (each, 1 mg/kg/day) 17ß-estradiol (E2), ERß-agonist (DPN) or ERα-agonist (PPT) for 10 days, while male and sham-OVX rats received vehicle for 10 days. Then, rats received either acetaminophen (3 g/kg) or saline by orogastric gavage and were decapitated at 24th h. Blood samples were obtained to measure serum ALT, AST, BUN, creatinine levels. Liver and kidney samples were obtained for histopathologic examination and for analyzing levels of luminol- and lucigenin-chemiluminescence, glutathione and myeloperoxidase activity. KEY FINDINGS: Compared to their control groups, levels of AST, ALT, BUN, creatinine, hepatic and renal myeloperoxidase activity and chemiluminescence levels were increased, and hepatic glutathione level was decreased in acetaminophen-administered male groups, while ALT and hepatic chemiluminescence levels were not elevated in sham-OVX-rats. Both ER-agonists and E2 reduced BUN, creatinine and reversed all oxidative parameters in renal tissues of OVX-rats. Additionally, ERα-agonist reversed all hepatic injury parameters, while ERß-agonist elevated hepatic glutathione level. SIGNIFICANCE: Acetaminophen toxicity in female rats presented with a more preserved hepatic function, while renal toxicity was not influenced by sex or by the lack of ovarian hormones. Pretreatment with estrogen or ER agonists, via their antioxidant actions, provided protective effects on acetaminophen-induced hepatorenal toxicity.