Investigation of Cytotoxic Effects of Oxymetazoline on Lungs in a Rat Model of Rhinitis Medicamentosa.

BACKGROUND: Rhinitis medicamentosa, also known as 'rebound congestion,' is inflammation of the nasal mucosa caused by the overuse of topical nasal decongestants. Although local decongestants resolve the initial nasal obstruction, the overuse causes rebound obstruction. However, how the overuse of the decongestant causes rhinitis medicamentosa is not known. OBJECTIVES: Here, we show the intracellular effects of oxymetazoline, commonly used a local decongestant, on the cell death pathways. We also investigated the antioxidative effects of erdosteine suspension (175 mg/5mL), an antioxidative agent. METHODS: Thirty Wistar-albino rats were used to form the rhinitis medicamentosa model. After rhinitis medicamentosa was clinically detected, we removed the whole lungs of animals to perform the molecular analyses of cell death pathways. RESULTS: We found a statistically significant decrease in the expression levels of Atg5 (p=0.021), Atg7 (p=0.013) and Ulk1 (p=0.036) in the oxymetazoline group compared to the control group (p<0.05); however, Caspase 3 expression level was recorded to be significantly increased in the oxymetazoline group, and the expression level of Beclin1 recorded to be substantially increased in the erdosteine group (p=0.001). CONCLUSION: Based on these grounds, we suggest that vasoconstriction in capillary vessels caused by oxymetazoline could lead to a decrease in the blood supply, which triggers autophagy to ensure cellular homeostasis.

The effects of bupivacaine combined with different adjuvants on block onset and duration and on ion channel expressions (SCN9A, TRPM) in sciatic nerve block in rats.

BACKGROUND/AIM: The objective of this experimental study was to examine the effects of epinephrine, dexmedetomidine, and clonidine added as adjuvants to bupivacaine on block onset and effect times, as well as the effects on the Na+ and Ca+2 channel gene expressions, which may indicate cell damage in the sciatic nerve cell membrane. MATERIALS AND METHODS: Rats were divided into five groups: Group S (sham), saline solution; Group B, bupivacaine; Group BD, bupivacaine + dexmedetomidine; Group BC, bupivacaine + clonidine; and Group BE, bupivacaine + epinephrine. For each group, 0.2 mL of local anesthetic was injected into the sciatic nerve bifurcation point of the right leg. Sensory (proprioceptive and nociceptive block) and motor block onset and ending times were recorded. RESULTS: The shortest onset time for the examined sciatic block was observed in the BC group, whereas the longest sensory and motor block times were observed in the BD group. The present data suggest suppressed TRPM7 and increased TRPM2 in the groups other than the BE group. CONCLUSION: Clonidine is more suitable for fast onset of peripheral nerve blocks, whereas the addition of dexmedetomidine is better in terms of duration. Because the SCN9A and TRPM2,4,7 expression ratios of the BE group showed the least amount of change, this group had the best cellular integrity.

Assessment of expressions of Bcl-XL, b-FGF, Bmp-2, Caspase-3, PDGFR-α, Smad1 and TGF-ß1 genes in a rat model of lung ischemia/reperfusion.

OBJECTIVES: Ischemia is described as organs and tissues are destitute of oxygen due to decreased arterial or venous blood flow. Many mechanisms play role in cell death happened as a consequence of a new blood flow is needed for both cell regeneration and to clean toxic metabolites during ischemia and later. Lung damage induced by ischemia/reperfusion (I/R) is a frequent problem in lung transplantation. Apoptosis (programmed cell death) is known as cell suicide, and plays a key role in embryonic developmental and in maintain adult tissue's life. MATERIALS AND METHODS: It is investigated expressions of Smad1, Bmp-2, Bcl-XL, b-FGF, Caspase-3, TGF-ß1, PDGFR-α genes for molecular changes in lung tissues, after I/R is formed, in this study. For this, we included 40 Wistar albino rats to this study and divided 4 groups (n=10). The Groups were determined as Control (C), Group 1= 1 hr ischemia (I), Group 2= 1 hr ischemia+2 hr reperfusion (I+2R), Group 3= 1 hr ischemia+4 hr reperfusion (I+4R). Besides, molecular analysis and histopathologic examinations of tissues were performed, and the results were evaluated by normalization and statistics analysis. RESULTS: We have found a significant increase in expression of Bcl-XL (P=0.046) and Caspase-3 (P=0.026) genes of group 1, and it was not monitored any significant difference in Group 2 and Group 3. In all groups, the changes in b-FGF (P=0.087), Bmp-2 (P=0.457), TGF-ß1 (P=0.201) and PDGFR-α (P=0.116) were not significant compared to control group. We did not see any mRNA expression of Smad1 gene in all groups include control. CONCLUSION: These findings suggest that I/R injury may trigger apoptotic mechanism in lung.

Histopathological features of bisphosphonates related osteonecrosis of the jaw in rats with and without vitamin d supplementation.

OBJECTIVE: Aim of this study was to investigate the effect of vitamin-D3 on the osteonecrosis of bone that was induced after tooth extraction was conducted on rats that were given zoledronic acid (Z.A). MATERIAL AND METHODS: Animals were divided into four groups. Two of the experimental groups were divided into two subgroups, third study group was not divided into subgroups, and control group was divided into three subgroups. Z.A was administered twice per week over the course of 7 weeks, dexamethasone was administered twice a week during the 5th-6th-7th weeks to all groups. Dental extraction was performed by drilling around the tooth at 7th week. In study-group-1; vitamin-D was administered twice per week during the 5th-6th-7th weeks. In study-group 2; vitamin-D was administered twice per week during the 8th-9th-10th weeks. In study-group-3; vitamin-D was administered twice per week during the 15th-16th-17th weeks. The animals were sacrificed at 10th-15th-17th weeks, and histologic samples were taken. RESULTS: Postoperative-15-group had a lower osteoblast number, which was statistically significant as compared to preoperative-15 and control-15-group. Control-10-group showed significantly lower osteoclast number in comparison to preoperative-10 and postoperative-10-group. Osteoclast number was significantly higher in the osteonecrosis-17-group as compared to control-17-group. Preoperative-10-group showed significantly higher inflammation in comparison to control-10-group. Postoperative-15-group had a lower histologic osteonecrosis, which was statistically significant as compared to the control-15-group. Macroscopic osteonecrosis was significantly higher in the control-17-group in comparison to the osteonecrosis-17-group. CONCLUSIONS: We concluded that there are some proofs for the treatment of BRONJ with systemic using of vitamin-D.

The effects of Nigella sativa oil, thymoquinone, propolis, and caffeic acid phenethyl ester on radiation-induced cataract.

BACKGROUND: The aim of this study was to investigate the antioxidant and radioprotective effects of propolis, caffeic acid phenethyl ester (CAPE), Nigella sativa oil (NSO), and thymoquinone (TQ) against ionizing radiation-induced cataracts in lens after total cranium irradiation of rats with single dose of 5-Gy cobalt-60 gamma rays. METHODS: A total of 74 Sprague-Dawley rats were divided into 8 groups to test the radioprotective effectiveness of Nigella sativa oil, thymoquine, propolis, or caffeic acid phenethyl ester administered by either orogastric tube or intraperitoneal injection. Appropriate control groups were also studied. RESULTS: Chylack's cataract classification was used in the study. At the end of the tenth day, cataracts developed in 80 % of the rats in the radiotherapy group. After irradiation, cataract rate dropped to 20 % in NSO, 30 % in propolis, 40 % in CAPE, and 50 % in TQ groups and was limited to grade 1 and grade 2. Cataract formation was observed the least in NSO group and the most in TQ group. In the irradiated (IR) group, superoxide dismutase activity was lower, while glutathione peroxidase and xanthine oxidase activities and malondialdehyde level were higher compared with the other groups. Total superoxide scavenger activity and nonenzymatic superoxide scavenger activity were not statistically significant in IR group compared with the other groups. CONCLUSIONS: The findings obtained in the study might suggest that propolis, CAPE, NSO, and TQ could prevent cataractogenesis in ionizing radiation-induced cataracts in the lenses of rats, wherein propolis and NSO were found to be more potent.

Histopathological Effects of Teriparatide in Medication-Related Osteonecrosis of the Jaw: An Animal Study.

PURPOSE: Osteonecrosis of the jaw after tooth extraction is a major complication in patients using bisphosphonates (BPs) for bone lesions, such as for the treatment of osteoporosis. The purpose of this study was to investigate the histopathologic effects of teriparatide (a synthetic parathyroid hormone) on rats developing osteonecrosis with BP use. MATERIALS AND METHODS: Rats (n = 80) that had been injected intraperitoneally with zoledronic acid for 7 weeks were used. Maxillary first molar extractions and bone defects were established in the same region in the eighth week. Teriparatide was administered subcutaneously to prevent osteonecrosis. Animals were sacrificed and histopathologic changes were examined. Osteoblasts, osteoclasts, inflammatory phase of bone healing, and osteonecrotic areas were evaluated. RESULTS: The osteoclast numbers were larger in the experimental groups (teriparatide administered before and immediately after tooth extraction) than in the control group (administered zoledronic acid). The inflammatory phase of bone healing was more pronounced in the experimental group (teriparatide administered before tooth extraction) than in the control group. There were significant differences in osteoclast numbers and in the inflammatory phase of bone healing between the experimental and control groups (P < .05). The osteoblast numbers and osteonecrotic areas were similar in size between the experimental and control groups. There were no significant differences (P > .05). CONCLUSIONS: BPs have negative effects on osteoclasts and the inflammatory phase of bone healing, whereas teriparatide was found to be effective in eliminating the negative effects of BPs. Teriparatide had positive effects in preventing osteonecrosis; therefore, teriparatide could be an effective agent for MRONJ.

Effects of laser irradiation at different wavelengths (660, 810, 980, and 1064 nm) on transient receptor potential melastatin channels in an animal model of wound healing.

The aim of the present study was to compare the effectiveness of four different laser wavelengths used for low-level laser therapy(LLLT) on healing of mucositis in an animal model of wound healing, by investigating expression of transient receptor potential melastatin(TRPM) ion channels. Forty-five rats were intraperitoneally injected with 100 mg/kg 5-fluorouracil on day 1 and 65 mg/kg on day 3. Superficial scratching on left cheek pouch mucosa was performed on days 3 and 5. After ulcerative mucositis was clinically detected, LLLT was started (660 nm, HELBO; 810 nm, Fotona-XD; 980 nm, ARC-Fox; and 1064 nm, Fidelis-Plus3) at 8 J/cm(2)/day from days 1 to 4. Oval excisional biopsy was performed at the wound site, and expression of TRPM2 to TRPM8 was evaluated. Student's t test was used for evaluation of significance of TRPM gene expression according to "0" value (α = 0.05). In 980-nm group, TRPM4, TRPM6, and TRPM7 were significantly higher than in the control group (p < 0.005). In 660, 810, and 1064 nm groups, only TRPM6 was significantly higher than in control group (p < 0.005). There were no significant differences between control and sham groups (p > 0.05). These findings suggest that expression of TRPM6 gene was significantly affected by irradiation with lasers at different wavelengths, whereas the TRPM4 and TRPM7 genes were only expressed in the 980-nm diode laser group. TRPM6 gene was highly expressed during LLLT, which may lead to accelerated wound healing and tissue repair. In contrast, there was some evidence that the 980-nm diode laser caused increased expression of TRPM4, TRPM6, and TRPM7 which are responsible for stimulation of Ca(2+) and Mg(2+) metabolism, as well as apoptotic pathways of controlled cell death.

Assessment of the effect of laser irradiations at different wavelengths (660, 810, 980, and 1064 nm) on autophagy in a rat model of mucositis.

It is known that high-dose radiation has an effect on tissue healing, but tissue healing does not occur when low dose radiation is applied. To clarify this issue, we compare the treatment success of low dose radiation with programmed cell death mechanisms on wounded tissue. In this study, we aimed to investigate the interactions of low and high-dose radiation using an autophagic mechanism. We included 35 adult Wistar-Albino rats in this study. All animals were injected with 100 mg/kg of 5-fluorouracil (5-FU) on the first day and 65 mg/kg of 5-FU on the third day. The tips of 18-gauge needles were used to develop a superficial scratching on the left cheek pouch mucosa by dragging in a linear movement on third and fifth days. After mucositis formation was clinically detected, animals were divided into five groups (n = 7). Different wavelengths of laser irradiations (1064 nm, Fidelis Plus, Fotona, Slovenia; 980 nm, FOX laser, A.R.C., Germany; 810 nm, Fotona XD, Fotona, Slovenia; 660 nm, HELBO, Medizintechnik GmbH, Wels, Austria) were performed on four groups once daily for 4 days. The laser irradiation was not performed on the control group. To get the tissue from the left cheek at the end of fourth day from all animals, oval excisional biopsy was performed. Molecular analysis assessments of pathological and normal tissue taken were performed. For this purpose, the expression analysis of autophagy genes was performed. The results were evaluated by normalization and statistics analysis. We found that Ulk1, Beclin1, and Atg5 expression levels were increased in the rats when the Nd:YAG laser was applied. This increase showed that a 1064-nm laser is needed to activate the autophagic mechanism. However, in the diode applications, we found that Beclin1, Atg10, Atg5, and Atg7 expressions numerically decreased. Atg5 is responsible for the elongation of autophagosome. Becn1 is a control gene in the control mechanism of autophagy. The reduction of the expression of these genes leads us to think that it may depend on the effect of drug (5-FU) used to form model. Expressions of therapeutic genes increase to ensure hemostasis, but in our study, expressions were found to decrease. More detailed studies are needed.

Evaluation of effects of T and N type calcium channel blockers on the electroencephalogram recordings in Wistar Albino Glaxo/Rij rats, an absence epilepsy model.

OBJECTIVES: It is suggested that excessive calcium entry into neurons is the main triggering event in the initiation of epileptic discharges. We aimed to investigate the role of T and N type calcium channels in absence epilepsy experimental model. MATERIALS AND METHODS: Wistar Albino Glaxo/Rij (WAG/Rij) rats (12-16 weeks old) were randomly allocated into four groups; sham, mibefradil (T type calcium channel blocker), w-Conotoxin MVIIA (N type calcium channel blocker), and mibefradil + w-Conotoxin MVIIA. Beta, alpha, theta, and delta wave ratios of EEG recordings and frequency and duration of spike wave discharges (SWDs) were analyzed and compared between groups. RESULTS: Beta and delta recording ratios in 1 µM/5 µl mibefradil group was significantly different from basal and other dose-injected groups. Beta, alpha, and theta recordings in 0.2 µM/5 µl w-Conotoxin MVIIA group was significantly different from basal and other dose-injected groups. In w-Conotoxin MVIIA after mibefradil group, beta, alpha, and theta recording ratios were significantly different from basal and mibefradil group. Mibefradil and w-Conotoxin MVIIA significantly decreased the frequency and duration of SWDs. The decrease of frequency and duration of SWDs in mibefradil group was significantly different from w-Conotoxin MVIIA group. The frequency and duration of SWDs significantly decreased in w-Conotoxin MVIIA after mibefradil group compared with basal, mibefradil, and w-Conotoxin MVIIA groups. CONCLUSIONS: We concluded that both T and L type calcium channels play activator roles in SWDs and have positive effects on frequency and duration of these discharges. These results are related with their central effects more than peripheral effects.

Effects of low-level laser therapy on changes in inflammation and in the activity of osteoblasts in the expanded premaxillary suture in an ovariectomized rat model.

BACKGROUND AND OBJECTIVE: Osteoporosis is a progressive systemic skeletal disease characterized by reduced bone mass/density and microarchitectural deterioration of bone tissue. Bone formation initially exceeds bone resorption, but by the third decade, such formation is reversed, resulting in a net loss of bone mass. This resorption, in turn, increases bone fragility and susceptibility to fracture. This study aimed to evaluate the effects of low-level laser therapy (LLLT) on bone regeneration in the expanded premaxillary suture in an ovariectomized rat model. METHODS: Thirty-two 12-week-old female Wistar albino rats were used in the experiment. All of the animals underwent ovariectomy 3 months before the experiment. Expansion appliances were affixed to the maxillary incisors for the expansion of premaxillary sutures. The premaxillary sutures of the laser group were exposed to 5 J/cm(2) laser energy, and no treatment was performed for the controls. All the rats in both groups were euthanized on either the 7th day (n=8) [end of expansion period; Laser Group 1(LG1) and Control Group 1 (CG1)] or the 17th day (n=8) [end of retention period; Laser Group 2 (LG2) and Control Group 2 (CG2)], respectively, for histological assessment. RESULTS: Histological findings indicated that the LG1 group showed a significantly higher number of osteoblasts than did the CG1 group (p=0.028). The CG1 and CG2 groups showed a significantly higher number of osteoclasts than did the LG1 and LG2 groups, respectively (p=0.005), (p=0.032). The LG2 group exhibited a capillary increase similar to that of the other groups, without statistically significant differences. CONCLUSIONS: On the basis of our methodology and results, we conclude that low-level laser associated with rapid maxillary expansion influences bone regeneration in sutures, thereby accelerating healing, even in ovariectomized rats. We found that LLLT decreased osteoclastic activity in the ovariectomized rats. Therefore, preventing osteoporosis necessitates further investigations to clarify the effect of LLLT on postmenopausal patients.

The radioprotective effect of Nigella sativa on nitrosative stress in lens tissue in radiation-induced cataract in rat.

OBJECTIVE: The aim of this study was to investigate the antioxidant and radioprotective effects of Nigella sativa oil (NSO) and thymoquinone (TQ) against ionizing radiation-induced cataracts in lens after total cranium irradiation (IR) of rats with a single dose of 5 gray (Gy). MATERIALS AND METHODS: Seventy-four Sprague-Dawley rats were used for the experiment. The rats were randomly divided into six groups. Group A received total cranium IR plus NSO (1 g kg(-1) d(-1)) orally through an orogastric tube. Group B received total cranium IR plus TQ (50 mgkg(-1) d(-1)) daily by intraperitoneal injection. Group C received 5 Gy of gamma IR as a single dose to total cranium plus 1 ml saline. Group D1 just received 1 ml saline. Group D2 just received dimethyl sulfoxide. Group D3 did not receive anything. RESULTS: At the end of the 10th d, cataract developed in 80% of the rats in IR group only. After IR, cataract rate dropped to 20% and 50% in groups which were treated with NSO and TQ, respectively, and was limited at grades 1 and 2. Nitric oxide synthase activity, nitric oxide and peroxynitrite levels in the radiotherapy group were higher than those of all other groups. CONCLUSIONS: The results implicate a major role for NSO and TQ in preventing cataractogenesis in ionizing radiation-induced cataracts in the lenses of rats, wherein NSO were found to be more potent.

Investigation of the effects of magnetic field exposure on febrile seizure latency, seizure duration, and electroencephalographic recordings in a rat febrile convulsion model.

AIM: To investigate the effects of a magnetic field (MF) on febrile seizure latency, seizure duration, and electroencephalographic (EEG) recordings in a rat febrile convulsion model. MATERIALS AND METHODS: Thirty-six rats were randomly allocated into 1 of 6 groups: sham group (S), febrile convulsion (FC) group without MF exposure, MF group without FC, group exposed to MF before FC (MF + FC), group exposed to MF after FC (FC + MF), and group exposed to MF before and after FC (MF + FC + MF). The rectal temperature after febrile seizure induction, seizure latency, seizure duration, and EEG recordings were recorded for all animals. RESULTS: Repeated hyperthermic exposure decreased the seizure latency and duration. The effect of the MF was more prominent on seizure duration than on latencies. MF exposure for 10 or 12 days increased seizure latency. MF exposure increased the pathologic theta and delta waves and decreased the beta waves, which are frequently seen in awake animals. CONCLUSION: Our results suggest that MF exposure has a negative effect on brain waves, and this effect becomes more evident with prolonged exposure. On the other hand, MF exposure significantly decreased the convulsion durations.

Evaluation of the safety of intracameral trypan blue injection on corneal tissue using oxidative stress parameters and apoptotic activity: an experimental study / Avaliação da segurança de injeção de azul de tripan intracameral no tecido da córnea utilizando parâmetros de estresse oxidativo e atividade apoptótica: um estudo experimental

Purpose: The present experimental study aimed to investigate the effects of intracameral trypan blue (TB) on oxidative stress parameters and apoptosis in corneal tissue. Methods: Thirty rats were randomly assigned to three groups of 10 rats each: the sham group (Group 1); control group (Group 2); and treatment group (Group 3). The control group was administered 0.01 cc of balanced salt solution. The treatment group was administered 0.006 mg/0.01 cc of TB. The total antioxidant status (TAS) and total oxidant status (TOS) in corneal tissue and blood were measured and the oxidative stress index (OSI) was calculated. Finally, corneal tissue histopathology was evaluated using staining for caspase-3 and -8, and apoptotic activity was examined. Results: The TAS, TOS and OSI levels in the blood samples were not significantly different (p>0.05 for all). Compared with the sham and control groups, the TOS and OSI levels in corneal tissue were significantly different in the treatment group (p<0.05 for all). No significant difference was observed between the sham group and the control group (p>0.05). Immunohistochemical staining for caspase-3 and caspase-8 demonstrated higher apoptotic activity in the TB group than in the sham and control groups. Conclusion: The present study showed that intracameral TB injection is safe systematically but may be toxic to corneal tissue, as demonstrated using oxidative stress parameters and histopathological evaluation. .

Objetivo: Este estudo experimental tem como objetivo investigar os efeitos do azul de tripan intracameral (TB) sobre parâmetros de estresse oxidativo e apoptose no tecido da córnea. Métodos: Trinta ratos foram divididos aleatoriamente em três grupos de 10 animais cada: grupo simulação (Grupo 1); grupo controle (Grupo 2); e grupo tratamento (Grupo 3). No grupo controle foi administrado 0,01 cc de solução salina balanceada (BSS). No grupo tratamento foi administrado 0,006 mg/0,01 cm de TB. O estado antioxidante total ( TAS) e estado oxidante total ( TOS) no tecido da córnea e sangue foram medidos e o índice de estresse oxidativo (OSI) foi calculado. Finalmente, histopatologia do tecido da córnea foi avaliada por meio da coloração para caspase-3 e -8; atividade apoptótica também foi examinada. Resultados: Os níveis de TAS, TOS e OSI das amostras de sangue não foram significativamente diferentes (p>0,05 para todos). Em comparação com os grupos simulação e controle, os níveis de TOS e OSI no tecido da córnea foram significativamente diferentes no grupo tratamento (p<0,05 para todos). Não houve diferença significativa entre o grupo simulção e o grupo controle (p>0,05). A coloração imuno-histoquímica com a caspase-3 e caspase-8 demonstrou maior atividade apoptótica no grupo tratamento do que nos grupos controle e simulação. Conclusão: Este estudo mostrou que a injeção intracameral TB é segura sistematicamente, mas pode ser tóxica ao tecido da córnea, como demonstrado através de parâmetros de estresse oxidativo e avaliação histopatológica. .

Effect of oral tamoxifen on the healing of corrosive oesophageal burns in an experimental rat model.

OBJECTIVES: Corrosive oesophagitis is a common health problem in children. Scar tissue can develop during the recovery period, and as a result, serious narrowing of the oesophagus can develop, in turn causing morbidity and mortality. In previous studies, it was argued that tamoxifen (TAM) may have antifibrotic effects beyond its oestrogen antagonist or agonist properties. We aimed to examine the possible effects of TAM on fibrosis and stricture formation, which are complications of corrosive oesophagitis. METHODS: Three study groups were formed as follows: a non-oesophageal burn group (NON-EB, n = 6), an oesophageal burn group (EB, n = 6) and an oesophageal burn + tamoxifen group (EB-TAM, n = 6). In the NON-EB rats, the oesophageal lumen was washed with 0.9% NaCl while, in the EB and EB-TAM rats, the distal oesophagus was burned with a 50% NaOH solution. After application of this solution to the EB-TAM group rats, 0.4 mg/kg/day of TAM was administered via gavage for 7 days. Twenty-two days later, the rat oesophagi were examined histopathologically for inflammation, granulation, collagen deposition and stenosis. RESULTS: In the EB group rats, the inflammation, collagen deposition and stenosis scores increased compared with those of the other groups. In the EB-TAM group, these three scores were lower compared with those of the EB group rats, but higher compared with those of the NON-EB group rats. No significant difference was observed in the granulation scores between the EB and EB-TAM groups. It was also observed that the EB-TAM group rats gained more weight than those in the EB group. CONCLUSIONS: According to the data obtained, TAM use prevents inflammation, collagenization and stricture development. TAM may be a useful medicine in the treatment of corrosive oesophagitis.

Expressions of TRPM6 and TRPM7 and histopathological evaluation of tissues in ischemia reperfusion performed rats.

There is very little work on the expression of TRPM6/7 in ischemia reperfusion models. In previous studies, after ischemia, reperfusion had been kept limited to 24 h, yet in our study, expressions of these channels were elucidated after its modification to 48 h to establish what kind of changes renal tissues undergo. For the current study, 20 Wistar albino rats were divided into two groups equally. Group I: control group, Group II = I/R group (60 min ischemia + 48 h reperfusion). For the mRNA analysis, right kidneys of I/R group was used as a reference in order to eliminate genetic differences. The left renal artery (I/R generated part) of I/R area was removed from all rats in the second group. Likewise, normal tissues of right renal artery were removed from all rats. Histopathologic scoring of the tissue samples were achieved semi-quantitatively according to normal tissue composition. Consequently, both TRPM6 and TRPM7 expression levels were decreased in all groups according to control groups, yet results were not counted as significant (p > 0.05). Additionally, correlation analysis confirmed these results. Also, I/R performed kidneys had more tissue damage compared to control group. To conclude, our study results suggest that TRPM6/7 expressions may be increased and after 48 h of reperfusion expression levels of these two stored to normal levels. At the same time, damages have occurred in renal tissues after ischemia. These damages were considered to be resulted from the oxidative effects as previously reported.

Palosuran treatment effective as bosentan in the treatment model of pulmonary arterial hypertension.

Pulmonary arterial hypertension (PAH) is a progressive and fatal disorder that any valuable advance in the management of diseases has crucial importance. The present study aimed to compare the Endothelin1 (ET1) inhibitor bosentan which is regarded as standard therapy with different dose regimens of palosuran which is urotensin-II (UII) inhibitor and explore the discrepancy for mean pulmonary arterial pressure (mPAP), UII, ET1 levels, and pulmonary vascular pathology. Seventy rats were randomly divided into seven groups of ten animals each: group 1 (control group) received the vehicle subcutaneously, instead of monocrotaline (MCT) and vehicle; group 2 (MCT group) received subcutaneous MCT and vehicle; and group 3 (MCT + palosuran 30 mg) received subcutaneous MCT and palosuran. Other groups consist of group 4 (MCT + palosuran 100 mg), group 5 (MCT + bosentan 30 mg), group 6 (MCT + bosentan 100 mg), and group 7 (combination therapy). Serum ET1, UII, mPAP levels, and pulmonary arteriolar pathology of different diameter vessels of all groups have been measured and recorded. The ET1 and UII levels of untreated rats (group 2) were significantly higher than the other groups (p < 0.05). Moreover, mPAP levels of group 2 were significantly higher than the other groups (p = 0.001). Finally, 50-125-µm diameter of arteriole wall thickness was found to be significantly thicker in monocrotaline group compared to groups 4 and 6 (p < 0.001). Statistical differences of wall thickness/diameter ratios of arteries and arterioles larger than 125 was found to be significant between group 5, group 6, and the control group (p < 0.001). UII inhibitor is at least as effective as standard therapy bosentan. Findings of this study consolidate that palosuran could be a new future promising therapeutic option in PAH.

Evaluation of TRPM (transient receptor potential melastatin) genes expressions in myocardial ischemia and reperfusion.

In the present study, the expression levels of TRPM1, TRPM2, TRPM3, TRPM4, TRPM5, TRPM6, TRPM7, and TRPM8 genes were evaluated in heart tissues after ischemia/reperfusion (IR). For this study, 30 albino male Wistar rats were equally divided into three groups as follows: Group 1: control group (n:10), Group II: ischemia group (ischemia for 60 min) (n:10) and Group III: IR (reperfusion 48 h after ischemia for 60 min and reperfusion for 48 h). The expression levels of the TRPM genes were analyzed by semi-quantitative reverse transcriptase-PCR. When compared to the ischemia control, the expression levels of TRPM2, TRPM4, and TRPM6 did not change, whereas that of TRPM7 increased. However, TRPM1, TRPM3, TRPM5, and TRPM8 were not expressed in heart tissue. Histopathological analysis of the myocardial tissues showed that the structures that were most damaged were those exposed to IR. The findings showed that there is a positive relationship between TRPM7 expression and myocardial IR injury.

Effects of laser irradiation at different wavelengths (660, 810, 980, and 1,064 nm) on mucositis in an animal model of wound healing.

The aim of the present study was to compare the effectiveness of four different laser wavelengths (660, 810, 980, and 1,064 nm) used for low-level laser therapy (LLLT) on the healing of mucositis in an animal model of wound healing by investigating the expression of platelet-derived growth factor (PDGF), transforming growth factor beta (TGF-ß), and blood-derived fibroblast growth factor (bFGF). Thirty-five male Wistar albino rats with a weight of 250-300 g body mass and 5 months old were used in the study. All animals were intraperitoneally injected with 100 mg/kg of 5-fluorouracil (5-FU) on the first day and 65 mg/kg of 5-FU on the third day. The tip of an 18-gauge needle was used in order to develop a superficial scratching on the left cheek pouch mucosa by dragging twice in a linear movement on third and fifth days. After ulcerative mucositis were clinically detected on the animals' left cheek pouch mucosa, the laser therapy was started. Four different laser wavelengths (660 nm, HELBO, Bredent; 810 nm, Fotona XD, Fotona; 980 nm, ARC Fox; and 1,064 nm, Fidelis Plus 3, Fotona) used for LLLT at ED 8 J/cm(2) daily from the first to the fourth days. Oval excisional biopsy was taken from the site of the wound, and the expression of PDGF, TGF-ß, and bFGF was evaluated. The obtained data were analyzed by one2-way ANOVA, and then Tukey HSD tests were used for pairwise comparisons among groups (α = 0.05). The one-way ANOVA test indicated that expression values of the growth factors, PDGF and bFGF, were significantly affected by irradiation of different wavelengths of lasers (p < 0.001). However, expression value of the TGF-ß was not affected by irradiation of different wavelengths of lasers (p > 0.05). The highest PDGF expression was detected in neodymium-doped yttrium aluminum garnet (Nd:YAG) laser group (p < 0.05), and there were no statistically significant differences among the other groups (p > 0.05). The highest bFGF expression was detected in 980-nm diode and Nd:YAG laser groups (p < 0.05), and there were no statistically significant differences among the other groups (p > 0.05). These findings suggest that low-level Nd:YAG and 980-nm diode laser therapy accelerate the wound healing process by changing the expression of PDGF and bFGF genes responsible for the stimulation of the cell proliferation and fibroblast growth.

The role of hepcidin and its related genes (BMP6, GDF-15, and HJV) in rats exposed to ischemia and reperfusion.

BACKGROUND/AIM: To determine the roles of hepcidin and its related genes in a renal ischemia/reperfusion model. MATERIALS AND METHODS: A total of 20 Wistar albino rats were equally divided into 2 groups: Group I was the control group and Group II was the ischemia and reperfusion (I/R) group (60 min of ischemia + 48 h of reperfusion). I/R was performed on the left kidneys of these rats and then the I/R-treated kidneys were removed. The levels of serum biochemical markers were evaluated after renal I/R. The expression levels of hepcidin-linked genes [growth differentiation factor 15 (GDF-15), bone morphogenetic protein 6 (BMP6), and hemojuvelin (HJV)] were also measured by RT-PCR technique. In addition, the tissues were evaluated histopathologically. RESULTS: No significant association was found between renal dysfunction and I/R when compared to biochemical parameters (P > 0.05). However, differences in platelet values were statistically significant (P < 0.05). Expression levels of GDF-15, BMP6, and HJV genes increased, but this increase was not statistically significant. In addition, histopathological evaluation was performed using hematoxylin and eosin stain. This showed a significant relationship between the control group and I/R group for ischemic and nonischemic kidney scoring. CONCLUSION: Hepcidin and BMP6, HJV, and GDF-15 should be taken into account when investigating the process of I/R.

Evaluation of the safety of intracameral trypan blue injection on corneal tissue using oxidative stress parameters and apoptotic activity: an experimental study.

PURPOSE: The present experimental study aimed to investigate the effects of intracameral trypan blue (TB) on oxidative stress parameters and apoptosis in corneal tissue. METHODS: Thirty rats were randomly assigned to three groups of 10 rats each: the sham group (Group 1); control group (Group 2); and treatment group (Group 3). The control group was administered 0.01 cc of balanced salt solution. The treatment group was administered 0.006 mg/0.01 cc of TB. The total antioxidant status (TAS) and total oxidant status (TOS) in corneal tissue and blood were measured and the oxidative stress index (OSI) was calculated. Finally, corneal tissue histopathology was evaluated using staining for caspase-3 and -8, and apoptotic activity was examined. RESULTS: The TAS, TOS and OSI levels in the blood samples were not significantly different (p>0.05 for all). Compared with the sham and control groups, the TOS and OSI levels in corneal tissue were significantly different in the treatment group (p<0.05 for all). No significant difference was observed between the sham group and the control group (p>0.05). Immunohistochemical staining for caspase-3 and caspase-8 demonstrated higher apoptotic activity in the TB group than in the sham and control groups. CONCLUSION: The present study showed that intracameral TB injection is safe systematically but may be toxic to corneal tissue, as demonstrated using oxidative stress parameters and histopathological evaluation.