The renoprotective effects of taurine against diabetic nephropathy via the p38 MAPK and TGF-ß/Smad2/3 signaling pathways.

Diabetic nephropathy (DN), a severe diabetes complication, causes kidney morphological and structural changes due to extracellular matrix accumulation. This accumulation is caused mainly by oxidative stress. Semi-essential amino acid derivative taurine has powerful antioxidant and antifibrotic effects. The aim of this study was to investigate the renoprotective effects of taurine through its possible roles in oxidative stress, extracellular matrix proteins, and the signaling pathways associated with the accumulation of extracellular matrix proteins in DN rats. 29 Wistar albino rats were randomly separated into control, taurine, diabetes, and diabetes + taurine groups. Diabetes animals were injected 45 mg/kg streptozosine. Taurine is given by adding to drinking water as 1% (w/v). Urine, serum, and kidney tissue were collected from rats for biochemical and histological analysis after 12 weeks. According to the studies, taurine significantly reduces the levels of malondialdehyde (MDA), total oxidant status (TOS), and protein expression of NADPH oxidase 4 (NOX4) that increase in diabetic kidney tissue. Also, decreased superoxide dismutase (SOD) activity levels significantly increased with taurine in diabetic rats. Moreover, increased mRNA and protein levels of fibronectin decreased with taurine. The matrix metalloproteinase (MMP)-2 and MMP-9 activities and their mRNA levels increased significantly, and this increase was significantly summed with taurine. There was a decrease in mRNA expression of Extracellular matrix metalloproteinase inducer (EMMPRIN). Taurine significantly increased this decrease. Diabetes increased mRNA expressions of transforming growth factor (TGF)-ß and Smad2/3. Taurine significantly reduced this induction. TGF-ß protein expression, p38, and Smad2/3 activations were also inhibited, but taurine was suppressed significantly. All these findings indicate that taurine may be an effective practical strategy to prevent renal diabetic injury.

Exposure to Fumes of a Vegetable Margarine for Frying: Respiratory Effects in an Experimental Model.

Deep frying is one of the strongest emission sources into indoor air. A vegetable margarine has recently been used in commercial kitchens. This study investigated the respiratory effects of exposure to its fumes in an experimental model. A setup with glass chambers was constructed. A chamber housed a fryer. The fumes were transported to the other chamber where 24 Wistar albino rats were placed in four randomized groups: acute, subacute, chronic, and control for the exposure durations. PM10 concentration in the exposure chamber was monitored to ensure occupational levels were obtained. Sacrification was performed 24 h after exposure. Lung, trachea, and nasal concha specimens were evaluated by two blinded histologists under a light microscope with hematoxylin-eosin. Mild mononuclear cell infiltration, alveolar capillary membrane thickening, alveolar edema, and diffuse alveolar damage, along with diffuse hemorrhage, edema, and vascular congestion in the interstitium were observed in the acute and subacute groups, and were overexpressed in the chronic group, whereas normal lung histology was observed in the control group. The results indicate that exposure to fumes of vegetable margarine for frying in commercial kitchens may cause pulmonary inflammation that becomes severe as the duration of the exposure increases.

Role of p38 MAPK, Akt and NFκB in renoprotective effects of nebivolol on renal ischemia-reperfusion injury in rats.

Renal ischemia-reperfusion (I-R) injury is a complex pathophysiologic condition characterized by oxidative stress, inflammation and apoptosis. We investigated the potential renoprotective effect of nebivolol, a ß1 adrenergic receptor blocker, against renal I-R injury. We focused on the role of nebivolol in activating p38 mitogen-activated protein kinase (MAPK) signaling, Akt (protein kinase B) and nuclear factor-κB (NFκB) transcription factors, which contribute to oxidative stress, inflammation and apoptosis during renal I-R. We divided 20 adult male Wistar albino rats into three experimental groups. Group 1 was a sham control in which only laparotomy was performed. Group 2 was the I-R group in which both kidneys were made ischemic for 45 min, then reperfused for 24 h. Group 3 was the I-R + nebivolol group in which 10 mg/kg nebivolol was administrated by gavage for 7 days before I-R. We measured Inflammation, oxidative stress and active caspase-3 as well as activation of p38 MAPK, Akt (protein kinase B) and NFκB transcription factor. Nebivolol significantly reduced oxidative stress and increased superoxide dismutase levels during renal I-R. We found that nebivolol significantly decreased interstitial inflammation, and TNF-α and interleukin-1ß mRNA expression. Nebivolol significantly reduced active caspase-3 and kidney injury molecule-1 (KIM-1) expressions. Nebivolol also significantly decreased activation of p38 MAPK signaling and NFκB, and induced Akt activation during renal I-R. Our findings suggest that nebivolol may be useful for management of renal I-R injury.

Therapeutic effects of melatonin on an ovalbumin-induced allergic rhinitis model in rats.

OBJECTIVE: We aimed to investigate the therapeutic effects of melatonin in an experimental AR model. METHODS: Thirty-two Wistar rats were randomised into four groups (n = 8 each). The experimental AR model was established in the saline (SF), ethanol, and melatonin groups via intraperitoneal (i.p.) injections and intranasal application of ovalbumin. The SF, ethanol, and melatonin groups received daily i.p. saline, 2% ethanol dissolved in saline, and 10 mg/kg melatonin dissolved in 2% ethanol and saline. The control group received the same amount of i.p. and intranasal saline. Total nasal symptom scores were recorded in all rats on days 1 (baseline), 15, 20, 25, and 30. Serum ovalbumin-specific IgE, IL-13, and melatonin levels were measured on days 1 (baseline), 15, and 30. The nasal mucosa of all rats was scored histopathologically. RESULTS: The total nasal symptom scores and serum ovalbumin-specific IgE values of the SF, ethanol, and melatonin groups were significantly higher on day 15 than those of the control group. On day 30, the scores and serum ovalbumin-specific IgE values of the melatonin group were similar to those of the control, whereas the SF and ethanol groups had statistically higher scores. The histological scores of the SF and ethanol groups were significantly higher than those of the control and melatonin groups, but no significant difference was found between the melatonin and control groups. CONCLUSION: Melatonin reduced total nasal symptom scores and serum ovalbumin-specific IgE levels and improved histological inflammation parameters in the ovalbumin-induced rat experimental AR model.

Alpha-lipoic acid alleviates colistin nephrotoxicity in rats.

Colistin methanesulfonate (CMS), a clinical form of colistin, is widely used as a last-line treatment for multidrug-resistant (MDR) gram-negative bacterial infections in critically ill patients presenting a considerably high mortality rate. However, nephrotoxicity is considered to be a critical adverse effect that limits CMS's clinical use. Alpha-lipoic acid (ALA) is a strong antioxidant that is effective in preventing nephrotoxicity in many models. The aim of this study was to investigate ALA's ability to protect against nephrotoxicity induced by colistin in rats. Male Wistar albino rats were randomly divided into four groups. Group 1 was the control group (Control; n = 6), in which isotonic saline was administered to the rats. Group 2 was the ALA group (ALA; n = 6) in which rats received 100 mg/kg ALA. Groups 3 was the CMS (CMS; n = 7) in which 450.000 IU/kg/day of CMS was administered to the rats. Groups 4 was the CMS + ALA group (n = 6), in which rats were injected with 100 mg/kg of ALA 30 min before administration of CMS. All injections were performed intraperitoneally at 1, 4, 7, and 10 days. Urine was collected by using a metabolic cage for 24 h after each administration. The rats were euthanized under ether anesthesia after 24 h of the last administration. Blood and kidney samples then were collected for histological and biochemical analysis. ALA pretreatment could reverse the effects of colistin-induced nephrotoxicity, partly through its suppressing effect on Nox4 and caspase-3, which in turn results in its antioxidant and antiapoptotic effect. Therefore, ALA may be an effective strategy for the management of colistin nephrotoxicity.

Alpha lipoic acid attenuates iron induced oxidative acute kidney injury in rats.

Iron has been implicated in oxidative tissue injury owing to its ability to generate reactive oxygen species (ROS). We investigated the reno-protective effects of alpha lipoic acid (ALA) by investigating its effects on the kidney isoform of NADPH oxidase (Nox4) and the specific signaling pathways, p38 MAPK and PI3K/Akt, which participate in apoptosis and survival, respectively. We established four groups of seven rats: control, 100 mg/kg ALA, 80 mg/kg iron sucrose (IS) and IS + ALA. IS and ALA were injected intravenously and rats were sacrificied after 6 h. The mRNA expression of the subunits of NADPH oxidase, Nox4 and p22phox; tumor necrosis factor-alpha (TNF-α); and kidney injury molecule-1 (KIM-1) were measured using quantitative real time polymerase chain reaction (qRT-PCR). Active caspase-3 protein expression was evaluated by immunostaining. Also, p38 MAPK and PI3K/Akt signaling pathways were analyzed using western blot. ALA suppressed the mRNA expression of Nox4, p22phox, TNF-α and KIM-1. Active caspase-3 protein expression induced by IS was decreased by ALA. ALA also suppressed p38 MAPK and activated the PI3K/Akt signaling pathway following IS administration. We found that ALA may be an effective strategy for preventing oxidative acute kidney injury caused by IS.

Evaluation of human pineal gland acetylserotonin O-methyltransferase immunoreactivity in suicide: A preliminary study.

Disorders of the serotonergic system are especially known to be present in the neurobiology of suicidal behavior. Studies investigating melatonin levels show that changes in pineal gland functions may also play a role in the pathogenesis of suicide. However, to our knowledge, there are no studies evaluating the activity of pinealocytes responsible for melatonin synthesis in suicide. This preliminary study aimed to investigate the relationship among pinealocyte, acetylserotonin O-methyltransferase (ASMT) immunoreactivity, and suicide. Samples of pineal gland, cerebrospinal fluid, blood, and urine were obtained from 21 suicide and 21 non-suicide cases on which medicolegal autopsies were performed. Expression of ASMT in human pineal gland was evaluated by immunohistochemical methods. A scoring system was used to define the anti-ASMT-positive staining in the sections. Enzyme-linked immunosorbent assays were employed to assess serum and cerebrospinal fluid melatonin levels and blood and urine noradrenaline levels. The ASMT-immunopositive pinealocyte count was observed to be lower in suicide cases compared to the non-suicide cases. With the exception of two cases (with moderate staining), all graded scores were 3 (strong staining) in non-suicide group, whereas scores were 1 (mild staining) or 2 (moderate staining) in the suicide group. Melatonin levels in the blood were lower among the suicide victims. These results support decreased pineal gland activity in suicide. However, further studies are needed to assess whether these changes are related to a psychiatric disorder.

Intranasal surfactant protein D as neuroprotective rescue in a neonatal rat model of periventricular leukomalacia.

BACKGROUND: Periventricular leukomalacia (PVL) is the leading cause of neurocognitive deficits in children with prematurity. We previously hypothesized that surfactant protein D (SPD) with its ability to bind toll-like receptors may have a possible ameliorating effect in PVL. METHODS: Three groups were defined as: LPS-administered and postnatal intranasal saline administered group, LPS-administered and postnatal intranasal SPD-treated group, and control group. Twenty-eight offspring rats were reared with their dams until their sacrifice for histological evaluation on day 7. RESULTS: A significant loss of brain weight occurred in the LPS group compared with controls. The postnatal intranasal SPD treatment significantly reduced the number of TUNEL-positive cells in the periventricular white matter as compared with the LPS-treated group. Compared with the control group, LPS injection in the rat brain significantly reduced the MBP-positive staining. Postnatal SPD treatment greatly prevented LPS-stimulated loss of MBP staining. CONCLUSIONS: Present study demonstrated a neuroprotective effect of SPD in a rat model of PVL. Our results offer future implications towards increasing our understanding about multifactorial mechanisms underlying periventricular leukomalacia and developing plausible therapeutic strategies in order to prevent neurocognitive deficits in preterm infants.

Evaluation of the effects of intra-arterial sugammadex and dexmedetomidine: an experimental study / Avaliação dos efeitos de sugamadex e dexmedetomidina intra-arterial: estudo experimental

Abstract Background: Intra-arterial injection of medications may cause acute and severe ischemia and result in morbidity and mortality. There is no information in the literature evaluating the arterial endothelial effects of sugammadex and dexmedetomidine. The hypothesis of our study is that sugammadex and dexmedetomidine will cause histological changes in arterial endothelial structure when administered intra-arterially. Methods: Rabbits were randomly divided into 4 groups. Group Control (n = 7); no intervention performed. Group Catheter (n = 7); a cannula inserted in the central artery of the ear, no medication was administered. Group Sugammadex (n = 7); rabbits were given 4 mg/kg sugammadex into the central artery of the ear, and Group Dexmedetomidine (n = 7); rabbits were given 1 µg/kg dexmedetomidine into the central artery of the ear. After 72 h, the ears were amputated and histologically investigated. Results: There was no significant difference found between the control and catheter groups in histological scores. The endothelial damage, elastic membrane and elastic fiber damage, smooth muscle hypertrophy and connective tissue increase scores in the dexmedetomidine and sugammadex groups were significantly higher than both the control and the catheter groups (p < 0.05). There was no significant difference found between the dexmedetomidine and sugammadex groups in histological scores. Conclusion: Administration of sugammadex and dexmedetomidine to rabbits by intra-arterial routes caused histological arterial damage. To understand the histological changes caused by sugammadex and dexmedetomidine more clearly, more experimental research is needed.

Resumo Justificativa: A injeção intra-arterial de medicamentos pode causar isquemia aguda e grave e resultar em morbidade e mortalidade. Não há informações na literatura que avaliem os efeitos endoteliais arteriais de sugamadex e dexmedetomidina. A hipótese de nosso estudo foi que dexmedetomidina e sugamadex causariam alterações histológicas na estrutura endotelial arterial quando administrados por via intra-arterial. Método: Os coelhos foram randomicamente divididos em quatro grupos: grupo controle (n = 7), sem intervenção; grupo cateter (n = 7), uma cânula foi inserida na artéria central da orelha e medicamentos não foram administrados; grupo sugamadex (n = 7), receberam 4 mg/kg de sugamadex na artéria central da orelha; grupo dexmedetomidina (n = 7), receberam 1 µg/kg de dexmedetomidina na artéria central da orelha. Após 72 horas, as orelhas foram amputadas e histologicamente examinadas. Resultados: Não houve diferença significativa entre os grupos controle e cateter referente aos escores histológicos. Os escores do dano causado ao endotélio e à membrana e fibra elásticas, da hipertrofia do músculo liso e do aumento do tecido conjuntivo foram significativamente maiores nos grupos dexmedetomidina e sugamadex do que nos grupos controle e cateter (p < 0,05). Não houve diferença significativa entre os grupos dexmedetomidina e sugamadex nos escores histológicos. Conclusão: A administração de sugamadex e dexmedetomidina a coelhos por via intra-arterial causou danos arteriais histológicos. Para entender as alterações histológicas causadas por sugamadex e dexmedetomidina com mais clareza, estudos experimentais adicionais são necessários.

Capparis ovata treatment suppresses inflammatory cytokine expression and ameliorates experimental allergic encephalomyelitis model of multiple sclerosis in C57BL/6 mice.

Since ancient times, Capparis species have been widely used in traditional medicine to treat various diseases. Our recent investigations have suggested Capparis ovata's potential anti-neuroinflammatory application for the treatment of multiple sclerosis (MS). The present study was designed to precisely determine the underlying mechanism of its anti-neuroinflammatory effect in a mouse model of MS. C. ovata water extract (COWE) was prepared using the plant's fruit, buds, and flower parts (Turkish Patent Institute, PT 2012/04,093). We immunized female C57BL/6J mice with MOG35-55/CFA. COWE was administered at a daily dose of 500mg/kg by oral gavage either from the day of immunization (T1) or at disease onset (T2) for 21days. Gene expression analysis was performed using a Mouse Multiple Sclerosis RT² Profiler PCR Array, and further determinations and validations of the identified genes were performed using qPCR. Whole-genome transcriptome profiling was analyzed using Agilent SurePrint G3 Mouse GE 8X60K microarrays. Immunohistochemical staining was applied to brain sections of the control and treated mice to examine the degree of degeneration. COWE was further fractionated and analyzed phytochemically using the Zivak Tandem Gold Triple Quadrupole LC/MS-MS system. COWE remarkably suppressed the development of EAE in T1, and the disease activity was completely inhibited. In the T2 group, the maximal score was significantly reduced compared with that of the parallel EAE group. The COWE suppression of EAE was associated with a significantly decreased expression of genes that are important in inflammatory signaling, such as TNFα, IL6, NF-κB, CCL5, CXCL9, and CXCK10. On the other hand, the expression of genes involved in myelination/remyelination was significantly increased. Immunohistochemical analysis further supported these effects, showing that the number of infiltrating immune cells was decreased in the brains of COWE-treated animals. In addition, differential expression profiling of the transcriptome revealed that COWE treatment caused the down regulation of a group of genes involved in the immune response, inflammatory response, antigen processing and presentation, B-cell-mediated immunity and innate immune response. Collectively, these results suggest anti-neuroinflammatory mechanisms by which COWE treatment delayed and suppressed the development of EAE and ameliorated the disease in mice with persistent clinical signs.

Evaluation of the effects of intra-arterial sugammadex and dexmedetomidine: an experimental study.

BACKGROUND: Intra-arterial injection of medications may cause acute and severe ischemia and result in morbidity and mortality. There is no information in the literature evaluating the arterial endothelial effects of sugammadex and dexmedetomidine. The hypothesis of our study is that sugammadex and dexmedetomidine will cause histological changes in arterial endothelial structure when administered intra-arterially. METHODS: Rabbits were randomly divided into 4 groups. Group Control (n=7); no intervention performed. Group Catheter (n=7); a cannula inserted in the central artery of the ear, no medication was administered. Group Sugammadex (n=7); rabbits were given 4mg/kg sugammadex into the central artery of the ear, and Group Dexmedetomidine (n=7); rabbits were given 1µg/kg dexmedetomidine into the central artery of the ear. After 72h, the ears were amputated and histologically investigated. RESULTS: There was no significant difference found between the control and catheter groups in histological scores. The endothelial damage, elastic membrane and elastic fiber damage, smooth muscle hypertrophy and connective tissue increase scores in the dexmedetomidine and sugammadex groups were significantly higher than both the control and the catheter groups (p<0.05). There was no significant difference found between the dexmedetomidine and sugammadex groups in histological scores. CONCLUSION: Administration of sugammadex and dexmedetomidine to rabbits by intra-arterial routes caused histological arterial damage. To understand the histological changes caused by sugammadex and dexmedetomidine more clearly, more experimental research is needed.

[Evaluation of the effects of intra-arterial sugammadex and dexmedetomidine: an experimental study]. / Avaliação dos efeitos de sugamadex e dexmedetomidina intra-arterial: estudo experimental.

BACKGROUND: Intra-arterial injection of medications may cause acute and severe ischemia and result in morbidity and mortality. There is no information in the literature evaluating the arterial endothelial effects of sugammadex and dexmedetomidine. The hypothesis of our study is that sugammadex and dexmedetomidine will cause histological changes in arterial endothelial structure when administered intra-arterially. METHODS: Rabbits were randomly divided into 4 groups. Group Control (n=7); no intervention performed. Group Catheter (n=7); a cannula inserted in the central artery of the ear, no medication was administered. Group Sugammadex (n=7); rabbits were given 4mg/kg sugammadex into the central artery of the ear, and Group Dexmedetomidine (n=7); rabbits were given 1µg/kg dexmedetomidine into the central artery of the ear. After 72h, the ears were amputated and histologically investigated. RESULTS: There was no significant difference found between the control and catheter groups in histological scores. The endothelial damage, elastic membrane and elastic fiber damage, smooth muscle hypertrophy and connective tissue increase scores in the dexmedetomidine and sugammadex groups were significantly higher than both the control and the catheter groups (p<0.05). There was no significant difference found between the dexmedetomidine and sugammadex groups in histological scores. CONCLUSION: Administration of sugammadex and dexmedetomidine to rabbits by intra-arterial routes caused histological arterial damage. To understand the histological changes caused by sugammadex and dexmedetomidine more clearly, more experimental research is needed.

Development, characterization, and in vivo assessment of mucoadhesive nanoparticles containing fluconazole for the local treatment of oral candidiasis.

This study aimed to develop a suitable buccal mucoadhesive nanoparticle (NP) formulation containing fluconazole for the local treatment of oral candidiasis. The suitability of the prepared formulations was assessed by means of particle size (PS), polydispersity index, and zeta potential measurements, morphology analysis, mucoadhesion studies, drug entrapment efficiency (EE), in vitro drug release, and stability studies. Based on the optimum NP formulation, ex vivo drug diffusion and in vitro cytotoxicity studies were performed. Besides, evaluation of the antifungal effect of the optimum formulation was evaluated using agar diffusion method, fungicidal activity-related in vitro release study, and time-dependent fungicidal activity. The effect of the optimum NP formulation on the healing of oral candidiasis was investigated in an animal model, which was employed for the first time in this study. The zeta potential, mucoadhesion, and in vitro drug release studies of various NP formulations revealed that chitosan-coated NP formulation containing EUDRAGIT(®) RS 2.5% had superior properties than other formulations. Concerning the stability study of the selected formulation, the formulation was found to be stable for 6 months. During the ex vivo drug diffusion study, no drug was found in receptor phase, and this is an indication of local effect. The in vitro antifungal activity studies showed the in vitro efficacy of the NP against Candida albicans for an extended period. Also, the formulation had no cytotoxic effect at the tested concentration. For the in vivo experiments, infected rabbits were successfully treated with local administration of the optimum NP formulation once a day. This study has shown that the mucoadhesive NP formulation containing fluconazole is a promising candidate with once-a-day application for the local treatment of oral candidiasis.

Effectiveness of sugammadex for cerebral ischemia/reperfusion injury.

Cerebral ischemia may cause permanent brain damage and behavioral dysfunction. The efficacy and mechanisms of pharmacological treatments administered immediately after cerebral damage are not fully known. Sugammadex is a licensed medication. As other cyclodextrins have not passed the necessary phase tests, trade preparations are not available, whereas sugammadex is frequently used in clinical anesthetic practice. Previous studies have not clearly described the effects of the cyclodextrin family on cerebral ischemia/reperfusion (I/R) damage. The aim of this study was to determine whether sugammadex had a neuroprotective effect against transient global cerebral ischemia. Animals were assigned to control, sham-operated, S 16 and S 100 groups. Transient global cerebral ischemia was induced by 10-minute occlusion of the bilateral common carotid artery, followed by 24-hour reperfusion. At the end of the experiment, neurological behavior scoring was performed on the rats, followed by evaluation of histomorphological and biochemical measurements. Sugammadex 16 mg/kg and 100 mg/kg improved neurological outcome, which was associated with reductions in both histological and neurological scores. The hippocampus TUNEL (terminal deoxynucleotidyl transferase dUTP nick end labeling) and caspase results in the S 16 and S 100 treatment groups were significantly lower than those of the I/R group. Neurological scores in the treated groups were significantly higher than those of the I/R group. The study showed that treatment with 16 mg/kg and 100 mg/kg sugammadex had a neuroprotective effect in a transient global cerebral I/R rat model. However, 100 mg/kg sugammadex was more neuroprotective in rats.

The effects of resveratrol against trifluralin toxicity in the urinary tract of rats.

The herbicide itself and the degradation products are highly toxic on biological systems. The aim of this study is to investigate the potential toxic effects of trifluralin (TRF) on the urinary system of male rats and to investigate the protective effects of resveratrol (RSV) in TRF-induced urinary system damage. A total of 35 male Wistar rats were randomly divided into: (1) control group, (2) sham group, (3) low dose TRF group (0.8 g/kg/day), (4) high dose TRF group (2 g/kg/day) and (5) high dose TRF + RSV group 10 mg/kg/day. RSV was administered for 21 days by intragastric gavage at a dose of 10 mg/kg/day after induction of TRF. Kidney, ureter and urinary bladder tissue was examined using light microscopy and ultrastructurally. Terminal deoxynucleotidyl transferase-mediated dUTP nick end labelling was performed to detect apoptosis. Superoxide dismutase (SOD), glutathion peroxidase (GPx) and malondialdehyde (MDA) levels were also evaluated biochemically for oxidative stress parameters. Histological evaluation showed that TRF increases apoptosis and oxidative stress, causes histological tissue damages and biochemical changes in the kidneys but does not cause any damage to the ureter and bladder. Treatment with RSV significantly attenuated tissue damage in the urinary system of rats. Apopitotic cells were significantly decreased in the treatment group. Additionally, treatment with RSV decreased SOD and GPx levels and increased MDA levels in the kidney tissue of animals subjected to TRF. These results show that RSV can significantly minimize histological damage and biochemical differences in treating TRF-induced kidney injury in rats.

Effective topical delivery systems for corticosteroids: dermatological and histological evaluations.

Atopic dermatitis (AD) is a chronic and relapsing skin disease with severe eczematous lesions. Long-term topical corticosteroid treatment can induce skin atrophy, hypopigmentation and transepidermal water loss (TEWL) increase. A new treatment approach was needed to reduce the risk by dermal targeting. For this purpose, Betamethasone valerate (BMV)/Diflucortolone valerate (DFV)-loaded liposomes (220-350 nm) were prepared and incorporated into chitosan gel to obtain adequate viscosity (∼13 000 cps). Drugs were localized in stratum corneum + epidermis of rat skin in ex-vivo permeation studies. The toxicity was assessed on human fibroblast cells. In point of in-vivo studies, pharmacodynamic responses, treatment efficacy and skin irritation were evaluated and compared with previously prepared nanoparticles. Liposome/nanoparticle in gel formulations produced higher paw edema inhibition in rats with respect to the commercial cream. Similar skin blanching effect with commercial creams was obtained via liposome in gels although they contain 10 times less drug. Dermatological scoring results, prognostic histological parameters and suppression of mast cell numbers showed higher treatment efficiency of liposome/nanoparticle in gel formulations in AD-induced rats. TEWL and erythema measurements confirmed these results. Overview of obtained results showed that liposomes might be an effective and safe carrier for corticosteroids in skin disease treatment.

Grape seed extract has superior beneficial effects than vitamin E on oxidative stress and apoptosis in the hippocampus of streptozotocin induced diabetic rats.

We aimed to investigate the effects of grape seed extract (GSE) and vitamin E (Vit E) on oxidative stress and apoptosis in the hippocampus of streptozotocin-induced diabetic rats. In Control, Diabetic, and Diabetic treated with GSE (Diabetic+GSE) and vitamin E (Diabetic+Vit E) groups, oxidative stress index (OSI), TUNEL staining and Bcl-2, Bcl-XL, Bax, caspase-3, -9, and -8, Cyt-c, TNF-α, and NF-κB gene expressions were evaluated. OSI was significantly increased in the plasma and hippocampus of the Diabetic compared to Control group and decreased in Diabetic+GSE and Diabetic+Vit E groups compared to Diabetic. TUNEL positive neurons significantly increased in the hippocampus of the Diabetic group compared to Control and decreased in Diabetic+GSE (more prominently) and Diabetic+Vit E groups compared to Diabetic. In the hippocampus of the Diabetic group, Bcl-2 and Bcl-XL gene expressions were significantly decreased; Bax, caspase-3, -9, and -8, Cyt-c, TNF-α, and NF-κB gene expressions were significantly increased compared to Control. In Diabetic+GSE and Diabetic+Vit E groups, Bcl-2 gene expressions were significantly increased; Bcl-XL gene expressions did not differ compared to the Diabetic group. The expression of Bax, caspase-3, -9, and -8, Cyt-c, TNF-α, and NF-κB genes in the Diabetic+GSE group and the expression of caspase-3 and -9, TNF-α, and NF-κB genes in the Diabetic+Vit E group were significantly decreased compared to Diabetic. In conclusion, GSE (more prominently) and vitamin E decreased oxidative stress and neuronal apoptosis occurring in the hippocampus of diabetic rats.

Zonisamide attenuates hyperoxia-induced apoptosis in the developing rat brain.

Oxygen therapy used in the treatment of perinatal hypoxia induces neurodegeneration in babies with immature antioxidant mechanisms. Zonisamide is a new antiepileptic drug used in childhood intractable seizures. Many studies demonstrated its neuroprotective effects. There is no study evaluating its effect on hyperoxic brain injury. The aim of this study was to investigate the neuroprotective effect of zonisamide on hyperoxia-induced neonatal brain injury. A total of 21 Wistar rat pups were used. The animals were divided into three groups: control group, hyperoxia group, and zonisamide-treated group. The zonisamide-treated group received an intraperitoneal injection of zonisamide. Zonisamide significantly preserved the number of neurons in CA1 and dentate gyrus parts of hippocampus, prefrontal, and parietal cortex. Zonisamide treatment also decreased the number of apoptotic neurons in all examined parts of hippocampus, prefrontal, and parietal cortex. We suggest that zonisamide treatment may be used as a neuroprotective agent in hyperoxic brain injury.

Effects of topical intranasal doxycycline treatment in the rat allergic rhinitis model.

OBJECTIVES: Allergic rhinitis (AR) is a chronic upper respiratory tract disease that inflames the mucous membranes of the nose and occurs when circulating inflammatory cells including eosinophils and basophils migrate to and accumulate in the inflammation area by passing through the interstitium and capillary walls. To pass through these barriers, the inflammatory cells degrade extracellular matrix proteins. Matrix metalloproteinases (MMPs) released by inflammatory cells mediate the degradation of these proteins. MMPs have synthetic inhibitors and doxycycline, a tetracycline antibiotic, inhibits MMPs. This study investigated the efficiency of intranasal doxycycline in decreasing the symptoms and inflammatory cell infiltration in an animal model of AR. METHODS: AR was created in female Wistar rats by repeated intranasal challenge with ovalbumin by intraperitoneal injection. For 15 days, topical intranasal doxycycline was administered one hour before ovalbumin administration. Following intranasal administration, nasal symptoms were scored and the nasal mucosae of all rats were evaluated histopathologically. To investigate tissue changes, hematoxyline-eosin and Alcian blue/periodic acid Schiff stains were used. As well, cilia loss, goblet cell changes, vascular congestion, vascular proliferation, inflammatory cell infiltration, eosinophil infiltration and the degree of hypertrophy in chondrocytes were evaluated with light microscopy. RESULTS: Typical symptoms of AR were decreased by intranasal doxycycline administration. These effects were stable after repeated intranasal ovalbumin administration. Histological evaluation of doxycycline treated rats did not reveal typical inflammatory changes associated with AR. CONCLUSION: MMPs may have crucial functions in AR and topical intranasal doxycycline, which decreases inflammatory cell infiltration, may offer an alternative therapy for AR.

Effect of induced hypothermia on lipopolysaccharide-induced lung injury in neonatal rats.

OBJECTIVES: Recent data suggest that induced hypothermia has some protective effects on experimental lung injury. We aimed to evaluate the protective effect of mild hypothermia in a rat model of lipopolysaccharide (LPS) induced neonatal lung injury. METHODS: Wistar rat pups were divided into four groups, specifically: (i) A control group, with no LPS administration and maintained in room air; (ii) A LPS group, with antenatal LPS administrated and maintained in room air; (iii) A LPS + hypothermia group, with antenatal LPS administrated and exposed to hypothermia; (iv) A hypothermia group, with no LPS administration and exposed to hypothermia. Intraperitoneal LPS was injected into maternal rats at the 19th and 20th gestational days to establish a neonatal lung injury model. Mild hypothermia was started at the postnatal 24th hour and continued during 24 h. At the postnatal 7th day, the rats were sacrificed and lung samples were evaluated for immunohistochemical tests and proinflammatory gene expression levels. RESULTS: Hypothermia therapy attenuated the damaging effects of antenatal LPS administration. Furthermore, hypothermia therapy reduced gene expression of pro-inflammatory cytokines (IL-6, IL-1α, IL-1ß, TNF-α) and induced the expression of a potent anti-inflammatory cytokine (IL-10). CONCLUSION: The results of this study indicated that mild hypothermia therapy is effective in an LPS induced neonatal lung injury model. If these results are supported by further studies, hypothermia may also be a new therapy option for preventing bronchopulmonary dysplasia.