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.

The effect of atorvastatin on lung histopathology in a murine model of chronic asthma.

INTRODUCTION: Atorvastatin is a statin group medicine that reduces the level of serum cholesterol; thus it is used to treat hypercholesterolaemia. Independent of the cholesterol-lowering property of statins they also have anti-inflammatory and immunomodulating effects. This study aimed to investigate the effect of atorvastatin on histological changes in the lungs in a murine model of chronic asthma. MATERIALS AND METHODS: Twenty-eight BALB/c mice in Group I, II, III and IV were divided into four groups. All the mice except the control group (Group I) were sensitised with ovalbumin. Intraperitoneal injection with saline, atorvastatin (10mg/kg), dexametazon (1mg/kg) was administered to Group II, Group III, and Group IV respectively for five consecutive days. Mice were sacrificed 24h after the last drug administration. All the histological properties of lung tissue samples from all groups were evaluated with light and electron microscopy. In addition, IL-4 and IL-5 levels of the lung tissue were measured. RESULTS: When Group II and Group III (atorvastatin) were compared, thicknesses of basement membrane and subepithelial smooth muscle layer, height of epithelium, number of mast and goblet cells were significantly lower in Group III. In comparing Group III (atorvastatin) and Group IV (dexamethasone), all the improvements in histological parameters were similar. In addition, the IL-4 and IL-5 levels of the lung tissue were significantly lower in atorvastatin group (Group III) compared to placebo-treated group. CONCLUSION: Atorvastatin had a beneficial effect on histological changes in a chronic murine model of asthma.

The effects of PPAR-γ agonist pioglitazone on renal ischemia/reperfusion injury in rats.

BACKGROUND: Acute renal failure due to renal ischemia/reperfusion (IR) injury is a significant clinical problem in cardiovascular surgery. Reactive oxygen species and inflammation play essential roles in the pathophysiology of IR injury. Matrix metalloproteinases (MMPs) are enzymes that play important roles in inflammation and mediate extracellular matrix degradation. It is known that peroxisome proliferator-activated receptor-γ agonists have antiinflammatory and antioxidant effects. In the present study, we aimed to investigate the effects of pioglitazone, a synthetic peroxisome proliferator-activated receptor-γ agonist, on MMPs and oxidative stress in a renal IR injury model in rats. MATERIALS AND METHODS: Male Wistar albino rats were divided into three groups: control (n = 7), placebo (n = 7; saline/p.o.), and pioglitazone (n = 7; 5 mg/kg/day/p.o.). In the control group, a right nephrectomy was conducted without left renal IR injury. In the placebo and pioglitazone groups, pretreatments were started 3 d before operation. In both groups, left renal pedicles were clamped for 60 min and then reperfused for 60 min. Paraffinized renal sections were evaluated histopathologically. Furthermore, expressions of MMP-2, MMP-9, tissue inhibitor of metalloproteinase (TIMP)-2, superoxide dismutase 1 (SOD1), and p47-phox/p67-phox subunits of NADPH oxidase were determined by immunostaining and scoring. RESULTS: In the placebo group, renal IR injury induced diffuse tubular necrosis and intense acute inflammation, but pioglitazone inhibited these effects. MMP-2, MMP-9, and TIMP-2 expression increased in the placebo group. However, while MMP-2 and -9 expression decreased, TIMP-2 expression did not change in the pioglitazone group. p47-phox/p67-phox expression increased in the placebo group, but SOD1 expression did not change. Pioglitazone diminished p47-phox/p67-phox expression, whereas it enhanced SOD1 expression. CONCLUSION: Our results suggest that pioglitazone might be helpful to reduce renal IR injury because of its antiinflammatory and antioxidant effects.

The effect of rupatadine on lung histopathology in a murine model of chronic asthma.

INTRODUCTION: Rupatadine is a new second-generation antihistamine with H(1) receptor antagonist activity and platelet-activating factor antagonist properties. This study aimed to investigate the effect of rupatadine on histologic changes in the lungs in a murine model of chronic asthma. MATERIALS AND METHODS: Thirty-five BALB/c mice were divided into five groups of seven mice each: group I (control), group II (placebo [saline]), group III (dexamethasone 1 mg · kg(-1)·d(-1)), group IV (rupatadine 3 mg·kg(-1) d(-1)), and group V (rupatadine 30 mg·kg(-1)·d(-1)). Groups II through V were sensitized and challenged with ovalbumin and treated once per day via the oral route (gavage). Animals were sacrificed 24 h after the last treatment was administered. Airway histopathology was evaluated using light and electron microscopy in all groups. RESULTS: There were no significant differences observed in any of the histologic parameters between groups II and IV. There were significantly thinner basement membrane, subepithelial smooth muscle layer, and epithelia were significantly thinner in group V than in group II (p < .05). There were no statistically significant differences in the thicknesses of the basement membrane, subepithelial smooth muscle layer and epithelia between groups III and V. CONCLUSION: Rupatadine had a beneficial effect on histologic changes in a chronic murine model of asthma.

Pioglitazone inhibits oxidative stress, MMP-mediated inflammation and vascular dysfunction in high glucose-induced human saphenous vein grafts.

AIMS: The aim of this study was to investigate the effects of pioglitazone on reactive oxygen species (ROS), expressions/activities of MMPs and TIMP-2, and VSMC proliferation and vascular reactivity in high glucose (HG)-induced human saphenous vein (HSV) grafts. METHODS: HSV grafts (n = 10) obtained from patients undergoing CABG were incubated with 30 mM glucose and/or 10 µM pioglitazone or 0.1 % DMSO for 24 h after endothelium removal. ROS levels were examined by chemiluminescence assay, MMP-2,-9,-14, TIMP-2, and α-SMA expression/activity was determined by gelatine zymography/immunohistochemistry. Vascular reactivity to potassium chloride, noradrenaline, serotonin, prostaglandin F2α and papaverine was assessed in HSVs. RESULTS: HG induced superoxide anion (SA) (123 %) and other ROS levels (159 %), up-regulated MMP-2 expression (180 %)/activity (79 %), MMP-14 expression (24 %) and MMP-9 activity while down-regulating TIMP-2 expression (27 %). HG elevated total MMP-2/TIMP-2 ratio (483 %) and MMP-14/TIMP-2 ratio (78 %). However, HG plus pioglitazone inhibited SA (30 %) and other ROS levels (29 %), down-regulated MMP-2 expression (76 %)/activity (83 %), MMP-14 expression (38 %) and MMP-9 activity, while reversing TIMP-2 expression (44 %). HG plus pioglitazone decreased total MMP-2/TIMP-2 ratio (91 %) and MMP-14/TIMP-2 ratio (59 %). HG impaired contractions to all agents but pioglitazone improved them. CONCLUSIONS: Pioglitazone may contribute to the prevention of restenosis and maintaining vascular function in HSV grafts of DM patients undergoing CABG.

The effects of α-lipoic acid against testicular ischemia-reperfusion injury in Rats.

Testicular torsion is one of the urologic emergencies occurring frequently in neonatal and adolescent period. Testis is sensitive to ischemia-reperfusion injury, and, therefore, ischemia and consecutive reperfusion cause an enhanced formation of reactive oxygen species that result in testicular cell damage and apoptosis. α-lipoic acid is a free radical scavenger and a biological antioxidant. It is widely used in the prevention of oxidative stress and cellular damage. We aimed to investigate the protective effect of α-lipoic acid on testicular damage in rats subjected to testicular ischemia-reperfusion injury. 35 rats were randomly divided into 5 groups: control, sham operated, ischemia, ischemia-reperfusion, and ischemia-reperfusion +lipoic acid groups, 2 h torsion and 2 h detorsion of the testis were performed. Testicular cell damage was examined by H-E staining. TUNEL and active caspase-3 immunostaining were used to detect germ cell apoptosis. GPx , SOD activity, and MDA levels were evaluated. Histological evaluation showed that α-lipoic acid pretreatment reduced testicular cell damage and decreased TUNEL and caspase-3-positive cells. Additionally, α-lipoic acid administration decreased the GPx and SOD activity and increased the MDA levels. The present results suggest that LA is a potentially beneficial agent in protecting testicular I/R in rats.

Vagus nerve bundle stimulation using 1505-nm laser irradiation in an in-vivo rat model.

Laser nerve stimulation using near-infrared laser irradiation has recently been studied in the peripheral nervous system as an alternative method to conventional electrical nerve stimulation. Bringing this method to the vagus nerve model could leverage this emerging stimulation approach to be tested in broader preclinical applications. Here, we report the capability of the laser nerve stimulation method on the rat vagus nerve bundle with a 1505-nm diode laser operated in continuous-wave mode. Studies of the stimulation threshold and laser-induced acute thermal injury to the nerve bundle were also performed to determine a temperature window for safe, reliable and reproducible laser stimulation of the rat vagus nerve bundle. The results show that laser stimulation of the vagus nerve bundle provides reliable and reproducible nerve stimulation in a rat model. These results also confirm a threshold temperature of >42°C with acute nerve damage observed above 46°C. A strong correlation was obtained between the laser time required to raise the nerve temperature above the stimulation threshold and the mean arterial pressure response. Advantages of the method such as non-contact delivery of external stimulus signals at mm scaled distance in air, enhanced spatial selectivity and electrical artefact-free measurements may indicate its potential to counteract the side effects of conventional electrical vagus nerve stimulation.

Design and in vitro, in vivo evaluation of antioxidant bioadhesive gels for burn treatment.

Burn wounds are frequently encountered health problems, which need a new treatment approach especially in terms of good patient compliance. Availability of use of antioxidant agents and bio-adhesive gels in tissue healing can be an alternative as a new approach for wound healing. Antioxidant taurine containing bio-adhesive gels were prepared by using carbopol (CP) 940 and 934. Rheological and texture analyses were carried out on bio-adhesive gels for in vitro characterization. Wound model on Wistar rats was used to evaluate the in vivo evaluation of gels. Rheological and texture analyses showed that a carbopol bioadhesive gel has acceptable topically use dosage characteristics and in combination with Taurine it presented a successful wound healing effect via antioxidant parameters. In conclusion, bio-adhesive CP 940 (2%) gel containing 50 mM taurine could be promising in the treatment of burns by balancing oxidative stress.

The beneficial effects of tadalafil on renal ischemia-reperfusion injury in rats.

Acute renal failure due to ischemia-reperfusion (I/R) injury is a common complication in cardiovascular surgery. We determined the influence of tadalafil on renal injury in a renal I/R model in rats. For this purpose, 21 male Wistar albino rats were separated into 3 groups: sham, placebo and tadalafil. A right nephrectomy was performed, and the left renal pedicles were occluded for 60 min and reperfused for 60 min in the placebo and tadalafil groups. A single dose of tadalafil (10 mg/kg) through an orogastric tube was administered to the tadalafil group. Tubular atrophy with acute inflammation in renal histology, total oxidant status (TOS) and total antioxidant status (TAS) were determined in tissue homogenates. Compared to the tadalafil group, tubular atrophy and acute inflammation was significant in the placebo group. TAS levels were significantly higher in the tadalafil group compared to the placebo (p = 0.01) and sham groups (p = 0.04). While TOS levels were significantly higher in the placebo group (p = 0.03), tadalafil did not significantly alter the TOS levels. The beneficial effects of tadalafil can be attributed to its protective effects on renal tubular cells and inhibition of leukocyte infiltration in renal tissue. We think that tadalafil treatment has an important role in reducing renal injury resulting from renal I/R.

Does carbon dioxide therapy really diminish localized adiposities? Experimental study with rats.

BACKGROUND: The probability of a positive effect of carbon dioxide (CO(2)) gas on the physiologic oxidative lipolytic process led to its use for localized adiposities. The authors considered that existing studies on CO(2) therapy were not sufficient to exhibit the efficiency of CO(2) therapy. The scientific basis for evaluating CO(2) therapy including standard dietary regimen, standard daily physical effort, and standard psychosocial stimuli was not clear. Despite this unclear situation, CO(2) therapy is extremely popular worldwide. The authors designed an experimental study using histomorphologic examination and the laser-Doppler flow meter to monitor treated tissue in rats. They devised a controlled applicator device appropriate for gas injection of rats and compared biochemical effects between CO(2) and breathable air. METHODS: In this study, 28 female Wistar rats weighing 300 g were divided into five groups: sham group, acute effect of CO(2) group, acute effect of breathable air group, chronic effect of CO(2) group, and chronic effect of breathable air group. Gas was injected into the right groin of the rats via a specially designed device. RESULTS: The bulging disappeared after approximately 30 min in the CO(2) injection groups but continued for more than 48 h in breathable air injection groups. The blood flow and velocity in terms of changes in the signals observed using the laser-Doppler technique did not demonstrate a significant increase in the values of the gas injection groups compared with the sham group 1. A statistical difference in the number of adipocytes was found between the groups. CONCLUSION: The study findings demonstrated a statistically significant decrease in adipocyte diameters during both the early and late phases of the subjects injected with CO(2). With adipocyte volume defined as an achievement, CO(2) therapy was found to be more successful than air injection. Furthermore, compared with the control group, the decrease in adipocyte volume also was statistically significant in breathable air injected groups (groups 3 and 5). This result suggests that the mechanical effects of gas injection are more important than the metabolic effects.

Glycyrrhizin and long-term histopathologic changes in a murine model of asthma.

BACKGROUND: Licorice root has been widely used to treat bronchial asthma for many years. However, the effect of this herb on lung histopathologic features is not fully understood. OBJECTIVE: In this study, we aimed to determine the effects of oral administration of glycyrrhizin, an active constituent of licorice root, on lung histopathologic features in BALB/c mice, in which the model of chronic asthma was established. METHODS: Twenty-eight BALB/c mice were divided into 4 groups: control, placebo, dexamethasone, and glycyrrhizin. Mice in the treatment and placebo groups were sensitized with 2 intraperitoneal injections of ovalbumin and then were exposed to aerosolized ovalbumin for 30 minutes per day on 3 days each week for 8 weeks beginning on the 21st study day. In the last week of inhalational exposure, mice in the placebo group received saline and those in the treatment groups received either dexamethasone, 1 mg/kg, or glycyrrhizin, 10 mg/kg, via orogastric gavage for 7 consecutive days. Animals were humanely killed 24 hours after the last ovalbumin and drug exposure. Lung histopathologic findings were evaluated using light and electron microscopy. RESULTS: As evaluated in the control, placebo, dexamethasone, and glycyrrhizin groups, respectively, the mean (SD) basement membrane thickness was 306.34 (36.91), 657.52 (98.99), 405.13 (96.1), and 465.01 (121.48) nm; subepithelial smooth muscle thickness was 7.22 (1.37), 11.24 (1.85), 5.62 (1.15), and 7.76 (1.11) µm; epithelium thickness was 19.48 (1.22), 41.62 (5.49), 22.59 (3.18), and 25.54 (4.68) µm; number of mast cells was 1.34 (0.19), 3.62 (0.5), 2.06 (0.77), and 2.77 (0.23)/16,400 µm(2); and number of goblet cells was 0.32 (0.1), 4.92 (0.82), 0.66 (0.06), and 0.98 (0.15)/100 µm. Evaluation of lung histopathologic features demonstrated that the chronic asthma model of mice was successfully established, with significantly higher numbers of goblet and mast cells and increased thickness of epithelium, basement membrane, and subepithelial smooth muscle layers (P < 0.001 for all) in the asthma group compared with in the control group. The number of goblet (P < 0.001) and mast (P < 0.02) cells and the thickness of basement membrane (P < 0.001), subepithelial smooth muscle layers (P ≤ 0.001), and epithelium of the lung (P < 0.001) were found to be significantly lower in the glycyrrhizin group compared with in the placebo group. When the glycyrrhizin and dexamethasone groups were compared, there was no statistically significant difference between the 2 groups in the histopathologic parameters, including thickness of basement membrane (P = 0.514), subepithelial smooth muscle (P = 0.054), and epithelium (P = 1.0) and number of mast (P = 0.075) and goblet (P = 0.988) cells. CONCLUSIONS: The results of this study suggest that the group receiving glycyrrhizin had amelioration of all established chronic histopathologic changes of lung in the mouse model of asthma. Further studies are needed to evaluate the efficacy of glycyrrhizin in the management of asthma.

The maxillary sinus after total laryngectomy: an electron microscopic study.

Nasal breathing is completely ceased after total laryngectomy. This results in some structural changes in the nasal mucosa, which has been described in numerous studies. This study investigates the changes that appear in the paranasal sinus mucosa. Eight patients who had undergone total laryngectomy at least 1-year ago were enrolled. Under general anesthesia, maxillary sinuses were examined with an endoscope inserted through canine fossa. 1-2 mm mucosal tissues for biopsy were taken from posterior wall of the maxillary sinus. Specimens were evaluated under an electron microscope. Control tissues for biopsy were obtained from two patients who had been operated for other reasons and analyzed under transmission electron microscopy. Results showed that in the control specimens, the epithelial cells appeared normal under transmission electron microscopy. Samples taken from two larygectomees in their first postoperative year were also completely normal. Samples from other larygectomees demonstrated ciliary loss, abundant degenerative vacuoles in ciliated epithelial cells and detachments in the interepithelial junctional complexes. The intracellular respiratory mechanisms such as the mitochondria, golgi complex and endoplasmic reticulum cisternae, and the integrity of the cellular or the nuclear membrane were spared. We conclude that the cessation of nasal breathing resulted in degenerative changes that could be reversible in the transmission electron microscopic examination of maxillary sinus mucosa. These changes emerged after 2 years following total laryngectomy. Nevertheless, these changes did not have any negative influence on the clinical outcome in this group of patients.

Melatonin Attenuates LPS-Induced Acute Depressive-Like Behaviors and Microglial NLRP3 Inflammasome Activation Through the SIRT1/Nrf2 Pathway.

Inflammation is a crucial component of various stress-induced responses that contributes to the pathogenesis of major depressive disorder (MDD). Depressive-like behavior (DLB) is characterized by decreased mobility and depressive behavior that occurs in systemic infection induced by Lipopolysaccharide (LPS) in experimental animals and is considered as a model of exacerbation of MDD. We assessed the effects of melatonin on behavioral changes and inflammatory cytokine expression in hippocampus of mice in LPS-induced DLB, as well as its effects on NLR Family Pyrin Domain Containing 3 (NLRP3) inflammasome activation, oxidative stress and pyroptotic cell death in murine microglia in vitro. Intraperitoneal 5 mg/kg dose of LPS was used to mimic depressive-like behaviors and melatonin was given at a dose of 500 mg/kg for 4 times with 6 h intervals, starting at 2 h before LPS administration. Behavioral assessment was carried out at 24 h post-LPS injection by tail suspension and forced swimming tests. Additionally, hippocampal cytokine and NLRP3 protein levels were estimated. Melatonin increased mobility time of LPS-induced DLB mice and suppressed NLRP3 expression and interleukin-1ß (IL-1ß) cleavage in the hippocampus. Immunofluorescence staining of hippocampal tissue showed that NLRP3 is mainly expressed in ionized calcium-binding adapter molecule 1 (Iba1) -positive microglia. Our results show that melatonin prevents LPS and Adenosine triphosphate (ATP) induced NLRP3 inflammasome activation in murine microglia in vitro, evidenced by inhibition of NLRP3 expression, Apoptosis-associated speck-like protein containing a CARD (ASC) speck formation, caspase-1 cleavage and interleukin-1ß (IL-1ß) maturation and secretion. Additionally, melatonin inhibits pyroptosis, production of mitochondrial and cytosolic reactive oxygen species (ROS) and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) signaling. The beneficial effects of melatonin on NLRP3 inflammasome activation were associated with nuclear factor erythroid 2-related factor 2 (Nrf2) and Silent information regulator 2 homolog 1 (SIRT1) activation, which were reversed by Nrf2 siRNA and SIRT1 inhibitor treatment.

Robust, Long-Term Culture of Endoderm-Derived Hepatic Organoids for Disease Modeling.

Organoid technologies have become a powerful emerging tool to model liver diseases, for drug screening, and for personalized treatments. These applications are, however, limited in their capacity to generate functional hepatocytes in a reproducible and efficient manner. Here, we generated and characterized the hepatic organoid (eHEPO) culture system using human induced pluripotent stem cell (iPSC)-derived EpCAM-positive endodermal cells as an intermediate. eHEPOs can be produced within 2 weeks and expanded long term (>16 months) without any loss of differentiation capacity to mature hepatocytes. Starting from patient-specific iPSCs, we modeled citrullinemia type 1, a urea cycle disorder caused by mutations in the argininosuccinate synthetase (ASS1) enzyme. The disease-related ammonia accumulation phenotype in eHEPOs could be reversed by the overexpression of the wild-type ASS1 gene, which also indicated that this model is amenable to genetic manipulation. Thus, eHEPOs are excellent unlimited cell sources to generate functional hepatic organoids in a fast and efficient manner.

Neuroprotective effects of selenium and ginkgo biloba extract (EGb761) against ischemia and reperfusion injury in rat brain.

OBJECTIVES: To determine the neuroprotective effects of Ginkgo biloba extract (EGb761) and Selenium (Se), and the combination of these agents on ischemia/reperfusion (I/R) injury in a rat model of transient global cerebral I/R. METHODS: This experimental study took place in the Animal Research Laboratory at Dokuz Eylul University, Izmir, Turkey in the year 2006. Fifty rats were subjected to cerebral I/R induced by right carotid artery occlusion technique for a duration of 45 minutes, and then were treated with EGb761 (50 mg/kg/day, ip) and Se (0.625 mg/kg, ip), alone or in combination for 14 days after surgery. Superoxide dismutase, and glutathione peroxidase activities were measured in the hippocampal tissues from 25 animals. Histopathological examinations were also carried out under light and electron microscopy from the rest of animals. RESULTS: The results suggest that EGb761 has a potent neuroprotective effect against cerebral I/R induced injury in rat brain that is comparable with that of Se. However, the combined use of EGb761 and Se does not further protect from neuronal injury when compared with the use of both agents alone. DISCUSSION: Our results suggest that administration of EGb761, Se and its combination with EGb761 have significant neuroprotective effects on I/R injury in rats via suppression of oxidative stress.

Suppression of apoptosis and oxidative stress by deprenyl and estradiol in aged rat liver.

Aging is accompanied by significant structural and functional transformations of all organs and systems. Age-associated increase in apoptotic behavior may cause disease. Older cells are more susceptible to endogenous oxidative damage, and oxidative stress is a potent inducer of apoptosis. Deprenyl is an irreversible monoamine-oxidase B inhibitor which has anti-oxidant, anti-apoptotic and neuroprotective effects. Estrogen is also a neuroprotective and anti-oxidant hormone. The objectives of this study were to determine whether the anti-oxidative effects of deprenyl can suppress apoptotic activity, with or without estradiol, in aged female rat livers. In this study, ovariectomized female Wistar albino rats were divided into six groups as follows; young (3 months old) saline-treated control, aged (24 months old) saline-treated control, aged deprenyl treated, aged estradiol treated, aged deprenyl plus estradiol treated and aged sham controls. All rats except for the sham group were treated for 21 days. Determination of oxidative stress parameters was performed spectrophotometrically. To detect apoptotic cells, TUNEL staining was performed. The results were analyzed by one-way ANOVA post hoc Bonferroni test. Deprenyl and estradiol administration, alone or in combination, decreased significantly the levels of lipid peroxidation and increased superoxide dismutase activity in the liver relative to aged control and sham rats (P<0.05). The number of TUNEL positive cells decreased significantly in deprenyl and estradiol-treated rats compared with aged control and sham rats. The results indicate that deprenyl treatment alone, or in combination with estradiol, may modulate age-related apoptotic changes in rat liver by decreasing oxidative stress.

The Effect of Autologous Platelet Rich Plasma in the Treatment of Achilles Tendon Ruptures: An Experimental Study on Rabbits.

BACKGROUND: Achilles tendon ruptures are characterized by a long recovery period, high re-rupture rate and late return to work. To overcome these difficulties and augment tendon repair, many agents have been used. AIMS: To determine the effect of autologous platelet rich plasma (PRP) in the treatment of Achilles tendon ruptures in rabbits. STUDY DESIGN: Animal experimentation. METHODS: The study included 14 New Zealand albino rabbits that were divided randomly into 2 groups, A and B, each containing seven rabbits. On day zero, all 28 Achilles tendons were tenotomized and repaired. In group A, the tendons were injected with PRP post-surgery, whereas those in group B were left untreated. On day 28, the right tendons in both groups were examined histopathologically via both light and electron microscopy, and the left tendons were subjected to biomechanical testing. RESULTS: The histological and biomechanical findings in both light and electron microscopy in group A were better than those in group B, but the difference was not significant. According to Tang's scale, the mean value in Group A was 3.57, while it was 3.0 in Group B. The mean value of Group A for the length of collagen bands was 48.09 nm while the mean value of Group B was 46.58 nm (p=0.406). In biomechanical tests, although stiffness values were higher in group A, the difference between groups was not significant. In addition, maximum load values did not differ between groups A and B. CONCLUSION: PRP had no effect on the healing process 28 days post-Achilles tendon rupture.

Resveratrol ameliorates 2,4-dinitrofluorobenzene-induced atopic dermatitis-like lesions through effects on the epithelium.

Background. Resveratrol is a natural polyphenol that exhibits anti-inflammatory effects. The aim of this study was to investigate the effects of resveratrol treatment on epithelium-derived cytokines and epithelial apoptosis in a murine model of atopic dermatitis-like lesions. Material and Methods. Atopic dermatitis-like lesions were induced in BALB/c mice by repeated application of 2,4-dinitrofluorobenzene to shaved dorsal skin. Twenty-one BALB/c mice were divided into three groups: group I (control), group II (vehicle control), and group III (resveratrol). Systemic resveratrol (30 mg/kg/day) was administered repeatedly during the 6th week of the experiment. After the mice had been sacrificed, skin tissues were examined histologically for epithelial thickness. Epithelial apoptosis (caspase-3) and epithelium-derived cytokines [interleukin (IL)-25, IL-33, and thymic stromal lymphopoietin (TSLP)] were evaluated immunohistochemically. Results. Epithelial thickness and the numbers of IL-25, IL-33, TSLP and caspase-3-positive cells were significantly higher in group II compared to group I mice. There was significant improvement in epithelial thickness in group III compared with group II mice (p < 0.05). The numbers of IL-25, IL-33, and TSLP-positive cells in the epithelium were lower in group III than in group II mice (p < 0.05). The number of caspase-3-positive cells, as an indicator of apoptosis, in the epithelium was significantly lower in group III than in group II mice (p < 0.05). Conclusion. Treatment with resveratrol was effective at ameliorating histological changes and inflammation by acting on epithelium-derived cytokines and epithelial apoptosis.

Effects of Quercetin Treatment on Epithelium-derived Cytokines and Epithelial Cell Apoptosis in Allergic Airway Inflammation Mice Model.

Quercetin is a dietary flavonoid which has anti-inflammatory effects. This study aimed to evaluate the influence of quercetin on histopathological aspects and airway epithelium in  allergic airway  inflammation mice model. Twenty-eight BALB/c mice were randomly divided into four groups: Group I (control), Group II (untreated mice with allergic airway inflammation), Group III (allergic airway inflammation quercetin-treated [16mg/kg/day]), Group IV (allergic airway inflammation dexamethasone-treated [1mg/kg/day]). Ovalbumin was administered intraperitoneally and via inhalation to achieve allergic airway inflammation mice model and treatments were also given intraperitoneally. Epithelium thickness, subepithelial smooth muscle thickness, number of mast and goblet cells, and basement membrane thickness were examined on samples isolated from lung. Immunohistochemical evaluationof lung tissues was performed using  IL-25, IL-33, thymic stromal lymphopoietin (TSLP), terminal deoxynucleotidyl transferase-mediated dUTP nick endlabeling (TUNEL) and cysteine-dependent aspartate-specific proteases(caspase)-3 antibodies. IL-4, IL-25, IL-33, TSLP were quantified in bronchoalveolar lavage (BAL) and OVAspecific IgE levels was measured in serum by standard ELISA protocols. IL-25, IL-33, thymic stromal lymphopoietin (TSLP) and cysteine-dependent aspartate-specific proteases (caspase)-3. Quercetin treatment led to lower epithelial thickness, subepithelial smooth muscle thickness, goblet and mast cell numbers compared to untreated  mice with allergic airway inflammation (p<0.05). However, quercetin treatment was not effective on improving basal membane thickness. Immunohistochemical scores of IL-25, IL-33, TSLP, caspase-3 and TUNEL were lower in quercetin-treated mice  t compared to untreated mice with allergic airway inflammation (p<0.05). IL-4, IL-25, IL-33, TSLP levels in BAL and OVA-specific IgE in serum were lower in quercetin treated mice compared to untreated mice (p<0.05). These findings suggest that quercetin improves chronic histopathological changes except basal membrane thickness in lung tissue and its beneficial effects on inflammation might be related to modulating epithelium derived cytokines and epithelial apoptosis.

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.