The effects of bee venom on liver and skeletal muscle in exhaustive swimming rats.

Oxidative damage and proinflammatory cytokines are involved in exhaustive exercise-induced fatigue. This study aimed to investigate the effects of bee venom, a natural toxin, on fatigue and tissue damage in rats that underwent forced swimming exercise. Rats were divided into four groups: control, swimming exercise (SE), bee venom (BV) and swimming exercise + bee venom (SE + BV). SE and SE + BV groups were subjected to forced swimming (load of 7% body weight) for 5 days. BV and SE + BV groups were injected with 1 mg/kg BV subcutaneously. Swimming time, blood lactate and TNF-α levels, MDA and GSH levels in liver and gastrocnemius muscle were evaluated. Swimming time was shorter in SE + BV group than SE group. There was no difference in lactate levels between SE and SE + BV groups. MDA and GSH levels were increased in SE, BV and SE + BV groups. TNF-α levels were increased in BV group compared to control and SE groups. Our study demonstrated that BV administration before exhaustive exercise in rats did not provide anti-fatigue effect. Additionally, BV did not show anti-inflammatory activity and had different effects on antioxidant capacity at tissue level. Further research might explore the effects of different doses and durations of BV on exhaustive exercise.

The Effects of Prenatal and Postnatal Exposure to 50-Hz and 3 mT Electromagnetic Field on Rat Testicular Development.

Background and objectives: It has been shown that electromagnetic fields (EMFs) have negative effects on the reproductive system. The biological effects of EMF on the male reproductive system are controversial and vary depending on the frequency and exposure time. Although a limited number of studies have focused on the structural and functional effects of EMF, the effects of prenatal and postnatal EMF exposure on testes are not clear. We aimed to investigate the effects of 50-Hz, 3-mT EMF exposure (5 days/wk, 4 h/day) during pre- and postnatal periods on testis development. Materials and Methods: Pups from three groups of Sprague-Dawley pregnant rats were used: Sham, EMF-28 (EMF-exposure applied during pregnancy and until postnatal day 28), EMF-42 (EMF-exposure applied during pregnancy and until postnatal day 42). The testis tissues and blood samples of male offspring were collected on the postnatal day 42. Results: Morphometric analyses showed a decrease in seminiferous tubule diameter as a result of testicular degeneration in the EMF-42 group. Follicle-stimulating hormone (FSH) and luteinizing hormone (LH) levels were decreased in the EMF-42 group. Lipid peroxidation levels were increased in both EMF groups, while antioxidant levels were decreased only in the EMF-28 group. We found decreased levels of vascular endothelial growth factor (VEGF) and insulin-like growth factor-1 (IGF1) in the EMF-42 group, and decreased levels of the SRC homology 3 (SH3) and multiple ankyrin repeat domain (SHANK3) in the EMF-28 group in the testis tissue. Conclusions: EMF exposure during pre- and postnatal periods may cause deterioration in the structure and function of testis and decrease in growing factors that would affect testicular functions in male rat pups. In addition to the oxidative stress observed in testis, decreased SHANK3, VEGF, and IGF1 protein levels suggests that these proteins may be mediators in testis affected by EMF exposure. This study shows that EMF exposure during embryonic development and adolescence can cause apoptosis and structural changes in the testis.

Direct kidney injury or lower extremity ischemia induced indirect kidney injury: Which one is more harmful for kidneys?

OBJECTIVES: The aim of this study was to investigate and compare the severity of kidney damage following lower limb ischemia-reperfusion and direct kidney ischemia-reperfusion. METHODS: Thirty Sprague Dawley male rats were randomly divided into three groups; lower extremity ischemia-reperfusion group (Group 2), renal ischemia-reperfusion group (Group 3) and control (anesthesia and median laparotomy only) (Group 1). In group 3, 1-h ischemia was performed on the kidney and in group 2, 1-h ischemia was performed on the left lower extremity. This procedure was followed by reperfusion for 24 h. Renal tissues were removed after the reperfusion period and the groups were evaluated for glutathioneperoxidase activity, malondialdehyde and GSH levels, and furthermore, their histolopathological scores were calculated. RESULTS: Renal malondialdehyde levels were significantly higher in Group 2 and Group 3 than they were in the Control group. There was no significant difference in renal malondialdehyde levels between Group 2 and Group 3. Kidney glutathione (GSH) levels were statistically lower in Group 2 and Group 3 than in the Control group. No statistically significant difference was found between Group 2 and Group 3 regarding their GSH levels. In histological evaluation, there was no statistically significant difference between Group 2 and Group 3 in terms of kidney damage score. CONCLUSIONS: This study has identified that lower extremity ischemia induces remote kidney damage with similar features to kidney injury, occurring after direct kidney ischemia-reperfusion.

Protective effect of alpha lipoic acid on 4-vinylcyclohexene diepoxide induced primary ovarian failure in female rats.

OBJECTIVE: The effects of alpha lipoic acid (ALA) and its possible mechanisms in treating Primary ovarian failure (POF) model was studied with 4 vinylcyclohexene diepoxide (VCD). MATERIAL AND METHODS: Rats were divided into 4 groups (n = 7) as Control, VCD, VCD + ALA and ALA. POF model was induced by applying VCD intraperitoneally and ALA was administered by oral gavage as 100 mg/day to the VCD + ALA and ALA groups. RESULTS: At the end of 42 days, ovarian and uterine tissues were received. The number of primordial and primary follicles were increased and corpus luteum and cystic follicles were decreased in ovarian tissues in VCD + ALA group compared to VCD group. Caspase-3 immunoreactivity in follicular cells was decreased in VCD + ALA group compared to VCD group. eNOS immunoreactivity and eNOS levels were decreased in VCD group and increased in VCD + ALA group while iNOS immunoreactivity and iNOS levels were increased in VCD group, decreased in VCD + ALA group in ovary and uterine tissue. Plasma FSH and LH hormone levels were increased in the VCD but decreased in VCD + ALA group. Estradiol level decreased in the VCD group compared to the other groups. The MDA values were significantly increased in the VCD + ALA group compared to VCD group. In addition, the levels of GSH values were decreased in VCD + ALA group compared to VCD group. CONCLUSION: Alpha lipoic acid treatment of rats with VCD-induced POF had a beneficial effect on reducing ovarian damage by improving histological, immunohistochemical, hormone level and oxidative stress markers. Our results show that ALA is an effective treatment of VCD-induced POF rats.

Which Distant Organ is Most Affected by Lower Extremity Ischemia-Reperfusion?

BACKGROUND: It has been experimentally shown that reperfusion injury occurs in many remote organs after ischemia-reperfusion (I/R) of the lower extremity. However, which distant organ is affected more after I/R of the lower extremity has not been investigated. In this study, we investigate which remote organ is predominantly affected after lower extremity I/R. METHODS: Twenty male Sprague-Dawley rats were randomly divided into 2 groups: sham (group 1) and lower extremity I/R (group 2). In group 2, 1 hr of ischemia of the left lower extremity was followed by 24 hr of reperfusion of the limb. After reperfusion, the lung, liver, kidney, heart, and small intestine tissues were harvested in both groups. RESULTS: In the I/R group, the malondialdehyde levels were significantly higher in the heart and small intestine tissues than those in other tissues (P < 0.05). In addition, in the I/R group, the glutathione and glutathione peroxidase activities were also higher in the heart tissues than those in other tissues (P < 0.05). However, these results were not significant because the malondialdehyde, glutathione, and glutathione peroxidase levels of the heart tissues in the control group were higher than those of the other tissues. Therefore, no statistically significant difference was found between the tissues in terms of the histological damage score we created and the terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling-positive cell numbers. CONCLUSIONS: There was no difference in the severity of reperfusion injury between the tissues we examined after lower extremity I/R. This suggests that every distal organ should be carefully monitored after lower extremity I/R.

Effects of Intraperitoneal Injection of Allogeneic Bone Marrow-derived Mesenchymal Stem Cells on Bronchiolitis Obliterans in Mice Model.

Bone marrow-derived mesenchymal stem cells (BMSCs) can ameliorate a variety of lung diseases such as asthma, lung fibrosis, and acute lung injury by its anti-inflammatory and immunmodulatory effects. In this study, we developed a mouse model of bronchiolitis obliterans (BO) and evaluated the effects of the intraperitoneal administration of BMSCs on lung histopathology and cytokine levels. 25 BALB/c mice were divided into four groups; control group (Group I), BO developed and 1x106 BMSCs-injected group (Group II), non-BO, 1x106 BMSCs-injected group (Group III), and BO developed and saline-injected group (Group IV). Histological and immunohistochemical findings of the lung tissue and the migration of BMSCs to the lung were evaluated using light and confocal microscopy techniques. Confocal microscopy evaluations showed that there was no noteworthy amount of BMSCs in the lung tissue of group III while significant amount of BMSCs was detected in group II. Wall thicknesses of terminal bronchiole and periterminal bronchiolar collagen deposition were significantly lower in group II compared to the group IV (p<0.05). Furthermore, according to the immunohistochemical staining results, CD3, CD4, CD8, CD20, CD68 and neutrophil elastase positive immune cells of group II were stained more positive than group IV cells (p<0.05). IFN-γ IL-2 and TNF-α levels in bronchoalveolar lavage fluid (BALF) were significantly lower in group II compared to group IV (p<0.05). The findings of this study indicate that intraperitoneally administered BMSCs have potent effects on histopatological changes of the lung tissue and cytokine levels in the murine model of BO.

Intraperitoneal mesenchymal stem cell administration ameliorates allergic rhinitis in the murine model.

Previous studies showed that bone marrow-derived mesenchymal stem cells (BMSCs) could ameliorate a variety of immune-mediated and inflammatory diseases due to their immunomodulatory and anti-inflammatory effects. In this study, we developed a mouse model of ovalbumin (OVA) induced allergic inflammation in the upper airways and evaluated the effects of the intraperitoneal administration of BMSCs on allergic inflammation. Twenty-five BALB/c mice were divided into five groups; group I (control group), group II (sensitized and challenged with OVA and treated with saline-placebo group), group III (sensitized and challenged with OVA and treated with 1 × 106 BMSCs), group IV (sensitized and challenged with OVA and treated with 2 × 106 BMSCs), and group V (sensitized and challenged with phosphate buffered saline (PBS) and treated with 1 × 106 BMSCs). Histopathological features (number of goblet cells, eosinophils and mast cells, basement membrane, epithelium thickness, and subepithelial smooth muscle thickness) of the upper and lower airways and BMSCs migration to nasal and lung tissue were evaluated using light and confocal microscopes. Levels of cytokines in the nasal lavage fluid and lung tissue supernatants were measured using enzyme-linked immunosorbent assay (ELISA). Confocal microscopic analysis showed that there was no significant amount of BMSCs in the nasal and lung tissues of group V. However, significant amount of BMSCs were observed in group III and IV. In OVA-induced AR groups (group II, III, and IV), histopathological findings of chronic asthma, such as elevated subepithelial smooth muscle thickness, epithelium thickness, and number of goblet and mast cells, were determined. Furthermore, the number of nasal goblet and eosinophil cells, histopathological findings of chronic asthma, and IL-4, IL-5, IL-13, and NO levels was significantly lower in both BMSCs-treated groups compared to the placebo group. Our findings indicated that histopathological findings of chronic asthma were also observed in mice upon AR induction. BMSCs migrated to the nasal and lung tissues following intraperitoneal delivery and ameliorated to the airway remodeling and airway inflammation both in the upper and lower airways via the inhibition of T helper (Th) 2 immune response in the murine model of AR.

Protective Effect of Korean Red Ginseng on Cisplatin Ototoxicity: Is It Effective Enough?

OBJECTIVE: The aim of our study was to investigate the effects Korean Red Ginseng (KRG) on cisplatin (CDDP) ototoxicity in vivo and in vitro. MATERIALS AND METHODS: The first part of the study was conducted on the House Ear Institute-Organ of Corti 1 (HEI-OC1) cell line. Cells were treated with CDDP, KRG, and their combination for 24 h. Cell viability, apoptosis, and the expression of 84 apoptosis-related genes were analyzed. In the second part of the study, 30 Wistar albino rats were divided into five groups. Baseline distortion product otoacoustic emissions (DPOAEs) and auditory brainstem response (ABR) measurements were obtained. In groups I, II, and III, only saline, KRG, and CDDP, respectively, were given. In group IV, 500 mg/kg KRG and in group V, 150 mg/kg of KRG were administered for 10 days. In groups III, IV, and V, 16 mg/kg CDDP injections were administered on day 11. On day 14, final DPOAEs and ABR measurements were completed. The rats were then sacrificed, and their inner ear structures were evaluated by transmission electron microscopy. RESULTS: In the first part of the study, pretreatment with 1 mg/mL KRG protected cells from CDDP ototoxicity. This protection was mainly due to a decline in apoptotic gene expression and an increase in antiapoptotic gene expression. In the in vivo part of the study, we found that both KRG doses had otoprotective effects. This protection was more prominent at the lower dose, especially on the spiral ganglion and the brainstem. CONCLUSION: KRG was shown to be an otoprotective agent against CDDP-induced ototoxicity both in vivo and in vitro.

Effects of administration of subtoxic doses of acetaminophen on liver and blood levels of insulin-like growth factor-1 in rats.

Acetaminophen (APAP) is widely used in the treatment of pain. Toxic doses of APAP cause acute liver failure, but therapeutic doses are believed to be safe. The purpose of this study is to investigate the effects of administration of subtoxic doses of APAP on liver and blood levels of insulin-like growth factor-1 (IGF-1) in rats. Low dose (100 mg/kg) and high dose (250 mg/kg) of APAP were intraperitoneally injected into Wistar albino rats. Following administration of therapeutic doses of APAP, there were no significant changes in serum transaminases and liver glutathione levels. Both doses of APAP induced a decrease in liver and blood levels of IGF-1 when compared with the controls. There was no significant difference in liver IGF-1 levels between the high-dose and low-dose APAP groups; however, there was a significant difference in blood IGF-1 levels between both the groups. The histological examination showed that low dose of APAP induced mild degree of structural change, while high dose of APAP induced severe structural damage. In conclusion, these results suggest that blood IGF-1 levels may have a value in predicting hepatic damage resulting from therapeutic doses of APAP.

Protective Effect of Acetyl-L-Carnitine Against Doxorubicin-induced Cardiotoxicity in Wistar Albino Rats.

BACKGROUND AND AIMS: Anthracyclines are one of the most preferred agents in practical pediatric oncology despite their dose-dependent cardiotoxic effects. The aim of this study was to investigate whether or not acetyl-L-carnitine (ALCAR) has protective effects on doxorubicin (DOX)-induced cardiotoxicity. METHODS: Wistar rats were divided into four groups; control, DOX, ALCAR and ALCAR+DOX. Rats in the first group were given saline on study days, whereas those in the second group were given a single dose of DOX on the 5th day and saline on the other days. Rats in the third group were given ALCAR and those in the fourth group were given ALCAR on study days but also given only a single dose of DOX on the fifth day of the study. Ejection fractions (EF) were measured by echocardiography before and after drug administration. Heart tissues were evaluated by light and electron microscopy. Apoptotic cells were determined with TUNEL and caspase-3 staining. RESULTS: DOX significantly decreased the EF values, whereas ALCAR did not. Cardiac functions were higher in the ALCAR+DOX group when compared to the DOX group. DOX administration caused a cardiac injury not only functionally, but also structurally, whereas ALCAR prevented it. CONCLUSIONS: ALCAR has a capacity of preventing DOX-induced cardiac injury at both functional and structural levels.

Investigation of iron's neurotoxicity during cerebral maturation in the neonatal rat model of haemolysis.

INTRODUCTION: Haemolytic disease of newborns due to rhesus and AB0 incompatibility is encountered frequently in neonatal clinics and may lead to severe haemolysis. In this study, it is suggested that important amounts of iron released with haemolysis may have a toxic effect on the brain parenchymal tissue, and the severity of the toxic effect can be correlated with the maturation of the brain barrier systems. To demonstrate the accumulation and the neuro-toxic effects of free iron (Fe) in the brain an experimental haemolysis model with various maturation phases was performed. MATERIAL AND METHODS: The study was composed of 48 Wistar rats with the following ages: five days old (Group A), 10 days old (Group B), and 19 days old (Group C). Each group was divided into three experimental subgroups and three control groups. Experimental groups were treated with intraperitoneal 75 mg/kg/day phenyl hydrazine hydrochloride for haemolysis. RESULTS: We demonstrated that the blood brain barrier (BBB) is permeable in five-day-old newborn rats and is mature in 10- and 19-day-old rats. Iron staining and neuronal damage were detected in group A and group B rats. No damage was detected in the brain tissue of group C animals. The presence of iron staining and neuronal damage in group B with mature BBB may suggest the existence of other incomplete barrier systems different from BBB that lead to iron accumulation in the brain. CONCLUSIONS: Blood brain barrier has a partial role in Fe transport, and the alternative barrier systems may also be involved. It could be supposed that after maturation of all barrier systems, excessive Fe penetration to the brain cannot occur. Our findings showed that the toxic amounts of iron may penetrate into the brain parenchyma of newborns despite the BBB preservation and cause neuronal damage in newborns, but the mature brain is not affected by the same magnitude blood levels.

Is there a gender-related susceptibility for cisplatin ototoxicity?

Ototoxicity is a well-known side effect of cisplatin. Some genetic and non-genetic risk factors were described for cisplatin ototoxicity. Although there are some studies which point out a sex-related difference for cisplatin nephrotoxicity and neurotoxicity, sex-related differences for cisplatin ototoxicity have not been studied. The aim of this study is to reveal whether there is any gender-related difference for susceptibility to cisplatin ototoxicity in rats. Fourteen male, 14 female Wistar albino rats were divided into four groups; a female control, a male control, a female cisplatin and a male cisplatin group. Distortion Product Otoacoustic Emission and, Auditory Brainstem Response measurements were obtained. For the cisplatin groups 16 mg/kg of cisplatin was applied. On the 4th day audiological examinations were repeated. After killing, cochleae and brainstem tissues were evaluated by light and electron microscopy. The hearing of the female rat cisplatin group was found to have deteriorated more than the hearing of the male rat cisplatin group. Histopathological evaluation revealed more serious damage in the spiral ganglion and brainstem tissues of female rats. Hearing of female rats deteriorated more than the hearing of male rats upon application of cisplatin. This difference in hearing can be attributed to the more severe damage seen in neuronal tissues such as spiral ganglion cells and brainstem neurons.

Potential novel biomarkers for diabetic testicular damage in streptozotocin-induced diabetic rats: nerve growth factor Beta and vascular endothelial growth factor.

BACKGROUND: It is well known that diabetes mellitus may cause testicular damage. Vascular endothelial growth factor (VEGF) and nerve growth factor beta (NGF-ß) are important neurotrophic factors for male reproductive system. OBJECTIVE: We aimed to investigate the correlation between testicular damage and testicular VEGF and NGF-ß levels in diabetic rats. METHODS: Diabetes was induced by streptozotocin (STZ, 45 mg/kg/i.p.) in adult rats. Five weeks later testicular tissue was removed; testicular VEGF and NGF-ß levels were measured by ELISA. Testicular damage was detected by using hematoxylin and eosin staining and periodic acid-Schiff staining, and apoptosis was identified by terminal-deoxynucleotidyl-transferase-mediated dUTP nick end labeling (TUNEL). Seminiferous tubular sperm formation was evaluated using Johnsen's score. RESULTS: In diabetic rats, seminiferous tubule diameter was found to be decreased; basement membrane was found to be thickened in seminiferous tubules and degenerated germ cells. Additionally, TUNEL-positive cells were increased in number of VEGF+ cells and levels of VEGF and NGF-ß were decreased in diabetic testes. Correlation between VEGF and NGF-ß levels was strong. CONCLUSION: These results suggest that the decrease of VEGF and NGF-ß levels is associated with the increase of the apoptosis and testicular damage in diabetic rats. Testis VEGF and NGF-ß levels could be potential novel biomarkers for diabetes induced testicular damage.

Friend or foe? Effect of oral resveratrol on cisplatin ototoxicity.

OBJECTIVES/HYPOTHESIS: Our objectives were to study effects of orally administered resveratrol (RV) against cisplatin (CDDP) ototoxicity in different doses and to investigate ultrastructural changes in the cochlea and brainstem. STUDY DESIGN: In vivo study using an animal model. METHODS: Thirty-two male Wistar albino rats were divided into six groups. Baseline distortion product otoacoustic emissions (DPOAEs) and auditory brainstem response (ABR) measurements were made. In groups I, II, and III, only saline, RV, and CDDP were given, respectively. Group IV, V, and VI animals were administered 10 mg/kg/day, 1 mg/kg/day, and 0.1 mg/kg/day of RV for 10 days, respectively, before 16 mg/kg CDDP injections were administered on day 11. All animals were sacrificed after repeated DPOAEs and ABR measurements were made on day 14. Cochleas of animals were investigated with transmission electron microscopy. Apoptosis were investigated with caspase-3 activity and terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL) method in the brainstem. RESULTS: In groups IV and V, DPOAEs and ABR findings revealed that oral administration of RV 10 mg/kg/day and 1 mg/kg/day doses before CDDP injection enhanced ototoxicity. In group VI, electomicroscopy revealed better ultrastructural findings than in the cisplatin group; however, these changes were not reflected in the audiological findings accordingly. CONCLUSIONS: Our results implied that there were noticeable differences between different oral RV doses used for cisplatin ototoxicity. Especially in higher doses, RV was observed to enhance cisplatin ototoxicity.

Comparison of TNF antagonism by etanercept and dexamethasone on airway epithelium and remodeling in an experimental model of asthma.

BACKGROUND: The aim of the study was to compare the influence of TNF antagonism and corticosteroid treatment on epithelial, smooth muscle and basement membrane component of airway remodeling in an experimental murine model of chronic asthma. METHODS: We used 30 BALB/c mice. Group 1 not exposed to ovalbumin or any medication was designated as control group. Chronic asthma model was achieved in the other three groups with intraperitoneal (IP) and inhaled ovalbumin. Then, Group 2 received IP saline, Group 3 received IP dexamethasone and Group 4 received IP etanercept. Epithelial, subepithelial smooth muscle and basement membrane thickness as well as goblet cells and mast cells were examined on samples isolated from left lung. RESULTS: Etanercept treatment led to thinner epithelial and basement membrane layer and lower goblet and mast cell number than untreated asthmatic mice (p<0.001, p=0.001, p=0.005 and p=0.03 respectively). Neither epithelial and basement membrane thickness nor mast cell number was different among mice treated with etanercept and dexamethasone (p=0.38, p=0.79 and p=0.51 respectively). However, etanercept group was associated with thicker subepithelial muscle layer but lower goblet cell number (p<0.001 and p=0.04 respectively) than dexamethasone group. CONCLUSIONS: Corticosteroids are more effective in decreasing smooth muscle mass while TNF antagonists in reducing goblet cell number in animal model of asthma. Therefore, further research is needed to assess the synergistic use of TNF antagonism and dexamethasone for more rational remodeling control.

Effect of 1α-25-dihydroxyvitamin D3 on intimal hyperplasia developing in vascular anastomoses: a rabbit model.

INTRODUCTION: A common problem encountered in routine daily practice of cardiovascular surgery is migration of smooth muscle cells leading to intimal hyperplasia developing at vascular anastomosis sites which then causes luminal narrowing. The aim of this study was to investigate the antiproliferative effect of 1,25 (OH)2D3 on intimal hyperplasia. MATERIAL AND METHODS: Twenty-one male white New Zealand rabbits weighing 2-3 kg were selected. There were 3 groups of animals each consisting of 7 rabbits. Group 1 was the control group. Group 2 was the sham group and group 3 consisted of rabbits receiving 1,25 (OH)2D3. The right carotid arteries of the subjects in groups 2 and 3 were transected and re-anastomosed. A daily dose of 25 ng 1,25 (OH)2D3 per 100 g body weight was administered for 14 days to rabbits in group 3. Rabbits in group 2 were not subject to any pharmaceutical agent. All the subjects were sacrificed at the end of the 28(th) postoperative day. Their right carotid arteries were resected and then investigated histopathologically. RESULTS: Intimal thickness and intimal area were measured as significantly lower in group 1 when compared with the other groups (p = 0.004). In group 3, the ratios of thickness of tunica intima/thickness of tunica media and area of tunica intima/area of tunica media were significantly lower than those of group 2 (p = 0.015, p = 0.003). CONCLUSIONS: 1,25 (OH)2D3, the active metabolite of vitamin D, reduces the intimal hyperplasia developing after vascular anastomoses.

Role of vascular endothelial growth factor antagonism on airway remodeling in asthma.

BACKGROUND: Vascular endothelial growth factor (VEGF) is an important mediator of the neoangiogenesis component of remodeling in asthma. OBJECTIVE: To evaluate the influence of VEGF blockage on airway remodeling, specifically epithelium thickness, subepithelial smooth muscle thickness, number of mast and goblet cells, and basement membrane thickness, in a mouse model of chronic asthma. METHODS: We used 30 BALB/c mice. The control group was not exposed to ovalbumin or any medication (group 1). Other groups were exposed to intraperitoneal and inhaled ovalbumin to achieve chronic asthma. Each of these groups received intraperitoneal saline (group 2), intraperitoneal dexamethasone (group 3), or intraperitoneal bevacizumab (group 4). Histomorphologic examination for epithelium thickness, subepithelial smooth muscle thickness, number of mast and goblet cells, and basement membrane thickness was performed from the middle zone of the left lung. RESULTS: Treatment with anti-VEGF caused significant reduction in epithelial, subepithelial muscle, and basement membrane thickness compared with untreated asthmatic mice (P = .001, P = .03, and P = .009, respectively). Goblet and mast cell numbers were significantly lower in mice treated with anti-VEGF than in untreated mice (P = .02 and P = .007, respectively). Dexamethasone treatment resulted in improvement of all histomorphologic markers, except goblet cell number. Influences of dexamethasone and anti-VEGF on epithelial and basement membrane thickness and mast and goblet cell numbers did not differ (P > .05), but subepithelial muscle layer was thinner in the former (P = .003). CONCLUSION: VEGF blockage may provide adjunctive therapeutic options as steroid-sparing agents for more effective treatment of remodeling in asthma.

Combined treatment with progesterone and magnesium sulfate positively affects traumatic brain injury in immature rats.

AIM: It is well known that head trauma results in damage in hippocampal and cortical areas of the brain and impairs cognitive functions. The aim of this study is to explore the neuroprotective effect of combination therapy with magnesium sulphate (MgSO4) and progesterone in the 7-days-old rat pups subjected to contusion injury. MATERIAL AND METHODS: Progesterone (8 mg/kg) and MgSO4 (150 mg/kg) were injected intraperitoneally immediately after induction of traumatic brain injury. Half of groups were evaluated 24 hours later, the remaining animals 3 weeks after trauma or sham surgery. Anxiety levels were assessed with open field activity and elevated plus maze; learning and memory performance were evaluated with Morris Water maze in postnatal 27 days. RESULTS: Combined therapy with progesterone and magnesium sulfate significantly attenuated trauma-induced neuronal death, increased brain VEGF levels and improved spatial memory deficits that appear later in life. Brain VEGF levels were higher in rats that received combined therapy compared to rats that received either medication alone. Moreover, rats that received combined therapy had reduced hipocampus and prefrontal cortex apoptosis in the acute period. CONCLUSION: These results demonstrate that combination of drugs with different mechanisms of action may be preferred in the treatment of head trauma.

Assessment of protective effects of pheniramine maleate on reperfusion injury in lung after distant organ ischemia: a rat model.

OBJECTIVE: The aim of this study is to investigate the protective effects of methylprednisolone (MP) and pheniramine maleate (PM) on reperfusion injury of lungs developing after ischemia of the left lower extremity of rats. MATERIALS AND METHODS: A total of 28 randomly selected male rats were divided into 4 groups, each consisting of 7 rats. Group 1 was the control group. Group 2 was the sham group (ischemia/reperfusion [I/R]). Rats in group 3 were subjected to I/R and given PM (Ph group) and rats in group 4 were subjected to I/R and given MP (Pn group). RESULTS: Malondialdehyde levels were significantly lower in Ph group than in I/R group (P < .05). Superoxide dismutase and glutathione peroxidase enzyme activities were found to be significantly higher in Ph group than in the I/R group (P < .05). Histological examination demonstrated that PM had protective effects against I/R injury. CONCLUSIONS: The PM has a protective effect against I/R injury in rat lung.

Serum IGF-1 levels correlate negatively to liver damage in diabetic rats.

Diabetes and insulin resistance frequently cause liver damage. Diabetes also causes reduction in liver and blood IGF-1 levels. We investigated the relation between liver damage and IGF-1 levels in diabetic rats. Fourteen Wistar albino rats were divided into control and diabetic groups. Diabetes was induced by streptozotocin. Rats were sacrificed for biochemical and histologic examinations 2 weeks after streptozotocin injection. Serum and liver IGF-1 levels were decreased, liver malondialdehyde (MDA) levels were increased, glutathione peroxidase (GPx) enzymes activities were decreased and serum alanine aminotransferase (ALT) levels were increased in diabetic group. Microscopic examination of liver revealed that normal tissue organization was disrupted in streptozotocin-induced diabetic rats. There was a strongly positive correlation between blood glucose levels and liver injury, and blood and liver IGF-1 levels. There was a strongly negative correlation between blood IGF-1 levels and hepatic injury. Our results suggest that reduction of blood IGF-1 levels correlates with hepatic injury and circulating IGF-1 levels may have predictive value for determining hepatic damage that results from diabetes. In addition, circulating IGF-1 levels are correlated with glutathione levels and the oxidative stress status of diabetic rat liver.