Investigation of the impact of antiparasitic drug moxidectin on the rewarding effects of alcohol.

Alcohol addiction or alcoholism constitutes a significant risk factor worldwide for morbidity and mortality. Moxidectin is a recently approved anthelmintic drug, which also activates the gamma-aminobutyric acid receptors. The objective of the present study was to examine the impact of moxidectin on rewarding effects of ethanol in the conditioned place preference (CPP) model in mice. In separate experiments, mice were administered intraperitoneal (i.p.) injections of moxidectin (5 or 10 mg/kg, i.p.) before a) acquisition of alcohol-induced CPP, b) each extinction session, and c) alcohol-induced reinstatement of CPP. The present experiments provide consistent data about ethanol place preference in mice (2 g/kg, i.p.), with mice in all tests spending significantly more time on the ethanol-paired side. The acquisition of the CPP response to ethanol was prevented by the administration of moxidectin at a dose of 10 mg/kg. Additionally, moxidectin treatment accelerated the extinction of ethanol CPP when given repeatedly during the extinction phase. Ethanol-induced reinstatement of CPP following an extinction phase was inhibited by moxidectin. Ethanol alone and co-administration with moxidectin did not change locomotor activity and motor coordination. In conclusion, we suggest that moxidectin may be a promising therapeutic candidate for prevention of ethanol-induced addiction and relapse as well as detoxification.

Effects of injectable platelet-rich fibrin in experimental periodontitis in rats.

Injectable platelet-rich fibrin (i-PRF) is an effective biological material that positively contributes to angiogenesis, wound healing, inflammation, regeneration processes, etc. This research aimed to evaluate the effect of i-PRF in rats with experimental periodontitis. Following the development of ligature-induced periodontitis, 24 Wistar albino rats were divided into three groups. Group-1: scaling and root planing (only-SRP); Group-2: SRP + i-PRF; Group-3: only- i-PRF. Heart blood from six donors was used for the i-PRF application. i-PRF was administered as a subgingival injection in the relevant groups on the 1st, 3rd, and 7th days. The tissues were evaluated histopathologically and immunohistochemically. Also, bone structures were examined using micro-CT. According to the data obtained, no statistically significant difference was observed among the groups in terms of bone resorption, inflammation, bone volume, bone levels (mesial/distal), and IL-1ß, IFN-ɤ, TNF-α, VEGF values (p > 0.05). However, bone mineral density was statistically significantly different among the groups (Group3 > Group2 > Group1) (p < 0.0001). Subgingival injection of only-i-PRF showed promising results in periodontitis treatment but contribution to SRP has not been proved according to this study results. The study results suggested that the i-PRF application was as effective as SRP in reducing bone loss, modulating inflammatory process, and effecting cytokines in experimental periodontitis. The significant effect of i-PRF on bone mineral density was the most remarkable result.

Influence of some ß-lactam drugs on selected antioxidant enzyme and lipid peroxidation levels in different rat tissues.

Antioxidant enzymes play an important role in body defense and free radical removal. Cephalosporins are ß-lactam antibiotics. In this work, the effects of cefazolin, cefuroxime and cefoperazone which are cephalosporins on some selected antioxidant enzyme and levels of malondialdehyde (MDA) as lipid peroxidation product were investigated in kidney, liver, and brain tissues of albino female rats. Ninety-six albino rats were randomly divided into 16 groups of equal number (n = 6). 50 mg/kg cefazolin, 25 mg/kg cefuroxime, and 100 mg/kg cefoperazone were injected intraperitoneally to the groups (5th-8th and 9th-12th, and 13th-16th groups), respectively. The changes in glutathione reductase (GR), glutathione S-transferase (GST), superoxide dismutase (SOD), peroxidase (POD), and glutathione peroxidase (GSH-Px) levels were studied in each time point group and a time-dependent manner (at the 1st, 3rd, 5th and 7th hour). In addition, MDA levels were examined in all the tissues. The drugs evaluated in this study had different effects on the same enzyme in different tissues depending on time. MDA levels especially in cefazolin and cefoperazone experiments were lower in all the tissues; however, MDA levels were higher in brain and kidney tissues in the cefuroxime groups in a time-dependent manner (p < 0.05). These results revealed the complex effects of the tested drugs on different tissues at different time points. Therefore, the dose and use of these drugs should be adjusted correctly.

Comparison of Enalapril, Candesartan and Intralesional Triamcinolone in Reducing Hypertrophic Scar Development: An Experimental Study.

BACKGROUND: The purpose of this study was to compare the effects of oral enalapril, an angiotensin-converting enzyme inhibitor (ACE-I), oral candesartan, an angiotensin receptor blocker (ARB), and intralesional corticosteroid treatments in reducing scar formation. METHODS: Twenty male rabbits were divided into five study groups: A (sham), B (control), C (ACE-I), D (ARB) and E (intralesional corticosteroid). The rabbit ear hypertrophic scar model was used. The hypertrophic scars were photographed and analyzed with the program ImageJ quantitatively to determine the degree of collagen fibers. The scar elevation index (SEI) was calculated at the end of the 40th day. Tissue samples were stained with hematoxylin and eosin and Masson's trichrome and examined under light microscopy for the determination of fibroblast number, epithelization, vascularization, inflammation and fibrosis. RESULTS: The SEI was the highest in the control group with the highest number of fibroblasts under the epithelium. In the steroid group, the SEI was significantly lower than both the ACE-I (p: 0.02) and ARB (p: 0.001) groups. The density of type 1 collagen fibers was the lowest in the control group, whereas type 3 collagen fibers were highest in that group. The ACE-I and ARB groups were similar regarding densities of type 1 and type 3 collagen fibers. The density of type 1 collagen fibers was the highest in the steroid group, whereas the density of type 3 collagen fibers was the lowest in that group. CONCLUSIONS: Enalapril, candesartan and intralesional steroid therapies were all effective in reducing scar tissue development; however, enalapril and steroid groups revealed better results. NO LEVEL ASSIGNED: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Paricalcitol may improve oxidative DNA damage on experimental amikacin-induced nephrotoxicity model.

This study aimed to investigate the possible protective effect of paricalcitol on experimental amikacin-induced nephrotoxicity model in rats. Wistar albino rats (n = 32) were allocated into four equal groups of eight each, the control (Group C), paricalcitol (Group P), amikacin-induced nephrotoxicity (Group A), and paricalcitol-treated amikacin-induced nephrotoxicity (Group A + P) groups. Paricalcitol was given intra-peritoneally at a dose of 0.4 µg/kg/d for 5 consecutive days prior to induction of amikacin-induced nephrotoxicity. Intra-peritoneal amikacin (1.2 g/kg) was used to induce nephrotoxicity at day 4. Renal function parameters, oxidative stress biomarkers, oxidative DNA damage (8-hydroxy-2'-deoxyguanosine/deoxyguanosine ratio), kidney histology, and vascular endothelial growth factor (VEGF) immunoexpression were determined. Group A + P had lower mean fractional sodium excretion (p < 0.001) as well as higher creatinine clearance (p = 0.026) than the amikacin group (Group A). Renal tissue malondialdehyde levels (p = 0.035) and serum 8-hydroxy-2'-deoxyguanosine/deoxyguanosine ratio (8-OHdG/dG ratio) (p < 0.001) were significantly lower; superoxide dismutase (p = 0.024) and glutathione peroxidase (p = 0.007) activities of renal tissue were significantly higher in group A + P than in group A. The mean scores of tubular necrosis (p = 0.024), proteinaceous casts (p = 0.038), medullary congestion (p = 0.035), and VEGF immunoexpression (p = 0.018) were also lower in group A + P when compared with group A. This study demonstrates the protective effect of paricalcitol in the prevention of amikacin-induced nephrotoxicity in an experimental model. Furthermore, it is the first study to demonstrate that paricalcitol improves oxidative DNA damage in an experimental acute kidney injury model.

Investigation of the effect of the efficiency of noise at different intensities on the DNA of the newborns.

Hearing loss can occur in newborns exposed to high-level noise; noise exposure can cause more physiological stress and can lead to DNA damage. This study was designed to determine DNA damage in newborn rats exposed to sound at different concentrations. For this purpose, 28 newborn (3-6 days old) rats were divided into four groups of 7 rats in each group (Control and Groups of 40 decibel (dB), 70 dB, and 110 dB]. In the experimental groups, 40 dB, 70 dB, and 110 dB (7.5-15 kHz) of sound was applied to the experimental groups for 30 min a day for 7 days. DNA damage levels in the serums obtained from this study were determined by the enzyme-linked immunosorbent assay (ELISA) method. According to this, it was determined that DNA damage in the group exposed to 110 dB showed a statistically significant increase (P < 0.05) compared to the compared to the control, 40 dB, and 70 dB groups. Related to the subject, it was concluded that DNA damage may occur in newborns exposed to 110 dB or higher sound in neonatal units, wards, and home environments with newborn babies. Mothers should be warned about this situation and noise should be kept under 110 dB volume in the environments with the newborns.

[Seroprevalence of tularemia in risk groups of humans and animals in Van, eastern Turkey]. / Van ili ve çevresinde risk altindaki insan ve hayvan gruplarinda tularemi seroprevalansi.

Tularemia has become a re-emerging zoonotic disease in Turkey recently. The aims of this study were to determine the seroprevalence of tularemia in humans and their animals living in rural risky areas of our region and to investigate the risk factors. Between January and July 2012, people living in rural areas of Van province (located at eastern part of Turkey) and their domestic animals were included in the study. The sample size was determined by using cluster sampling method like in an event with known prevalence and planned as a cross-sectional epidemiological study. Proportional random sampling method was used to determine which individuals will be included in the study. Presence of tularemia antibodies in the sera of a total 495 voluntary persons (343 female, 152 male; age range: 18-79 years, mean age: 40.61) and their 171 animals (40 cattle, 124 sheep and 7 goats) were screened by microagglutination test using safranin O-stained F.tularensis antigen (Public Health Agency of Turkey). For the evaluation of cross-reactivity between Brucella spp., tularemia positive serum samples were also tested with brucella microagglutination test. Among human and animal samples, 11.9% (59/495) and 44% (76/171) yielded positive results with the titers of ≥ 1:20 in F.tularensis microagglutination test, respectively. However, 69.5% (41/59) of human sera and 78.9% (60/76) of animal sera demonstrated equal or higher titers in the brucella test, so those sera were considered as cross-reactive. After exclusion of these sera, the seroprevalence for F.tularensis were calculated as 3.6% (18/495) for humans and 9.4% (16/171) for animals. Among the 16 animals with positive results, 12 were sheep, three were cattle and one was goat. The difference between seropositivity rates among the domestic animal species was not statistically significant (p> 0.05). In addition, no statistically significant differences were found between risk factors including insect bite, tick bite, contact with rodents, eating the meat of hunted animals (rabbit), having pet (cat) in home (p> 0.05). In this study, the rate of tularemia seropositivity among humans was similar to the results of previous studies which were performed in our country; however the seropositivity rate of tularemia among domestic animals in our study was higher than the results of a few studies which were conducted on domestic animals. In conclusion, preventive procedures and precautions must be taken into consideration to control the transmission of the infection.

Use of an antiarrhythmic drug against acute selenium toxicity.

OBJECTIVE: Selenium is an essential trace element. But, selenium may have toxic effects in high doses. There are no proven antidotes or curative treatments for acut selenium toxicity. Treatment involves stopping the exposure and providing supportive care for symptoms. Therefore, it is necessary to find more effective substances in the treatment of selenium toxicity. The aim of this study was to increase the survival rate of animals by supporting the heart with amiodarone and to determine the effect of amiodarone on the pathological, hematological and biochemical parameters in acute selenium intoxication. METHODS: 64 Wistar-Albino rats were divided into four groups. Group I was given only distilled water, Group II was given 18 mg/kg dose of amiodarone, Group III was given 18 mg/kg amiodarone and 10 mg/kg sodium selenite and Group IV was given sodium selenite 10 mg/kg (LD50 dose)orally. RESULTS: 11 of the 16 animals in Group IV died within the first 48 h of drug administration. However, no deaths were observed in the rats in Group III. No hematological changes were observed. Biochemically, CK, CK-MB and LDH levels of Group IV were higher than the other groups on both the 2nd and 10th days. In Groups II and III, this serum level decreased, and vitamin B12 levels increased. In macroscopic inspections of the organs of Groups III and IV, slight paleness was detected. Histopathologically, degenerative changes in tissue were observed, especially in Group IV. CONCLUSION: This study shows that amiodarone application has a reducing effect on selenium toxicity. This was because amiodarone protected the heart by reducing CK and CK-MB levels and increased vitamin B12 levels, which play a role in the synthesis of S-adenosyl methionine that converts selenium into a nontoxic form.

The effect of PDE5 inhibitors on bone and oxidative damage in ovariectomy-induced osteoporosis.

Osteoporosis is a major public health problem associated with many factors, and it affects more than 50% of women over 50 years old. In the current study, our purpose was to investigate the effects of phosphodiestarase-5 inhibitors on osteoporosis via the nitric oxide/3',5'-cyclic guanosine monophosphate/protein kinase G signalling pathway. A total of 50 female albino Wistar rats were separated into five groups. The first group was appointed as the healthy control group with no ovariectomy. All animals in the other groups underwent a bilateral ovariectomy. Six months after the ovariectomy, vardenafil, udenafil and tadalafil were given to the third, fourth and fifth groups, respectively, but were not administered to the positive control group (10 mg/kg per day for two months). The bone mineral density values were determined using a densitometry apparatus for all groups pre- and post-ovariectomy as well as after treatment. The levels of nitric oxide, endothelial nitric oxidesynthase, asymmetric dimethylarginine, 3',5'-cyclic guanosine monophosphate, protein kinase G, phosphodiestarase-5, pyridinoline, deoxypyridinoline, carboxyterminal telopeptide fragments and plasma carboxy terminal propeptide of type I collagen were determined using an enzyme linked immunosorbent assay. The levels of malondialdehyde, 8-hydroxy-2-deoxy guanosine, deoxyguanosine and coenzyme Q10 were determined by a high-performance liquid chromatography assay. Additionally, the right femoral trabecular bone density and the epiphyseal plate were measured in all groups. Angiogenesis was histologically observed in the bone tissue. In addition, we determined that the inhibitors may have caused a positive impact on the increased bone mass density and reduction of bone resorption markers. We also observed the positive effects of these inhibitors on oxidative stress. In conclusion, these phosphodiestarase-5 inhibitors increase angiogenesis in bone tissue and improve the re-formation rate of bone in rats with osteoporosis. Chemical compounds studied in this article Udenafil (PubChem CID: 6918523); Tadalafil (PubChem CID: 110635); Vardanafil (PubCham CID: 110634). Impact statement The results in our study appear to establish the osteoporosis model and provide evidence of the positive effects of three separate PDE5 inhibitors (vardenafil, udenafil, and tadalafil). The positive effects of these PDE5 inhibitors are investigated and demonstrated by the bone mass density and bone resorption markers. These effects are associated with significant demonstrated antioxidant activities. Osteoporosis is a significant major public health problem especially in more aged populations. Advances in identifying and understanding new potential therapeutic modalities for this disease are significant. This study provides such an advance.

Theophylline attenuates bleomycin-induced oxidative stress in rats: The role of IL-6, NF-κB, and antioxidant enzymes

Abstract The purpose of this study was to evaluate the antifibrotic and antioxidant roles of theophylline (Theo), a bioactive compound, in bleomycin (BLM)-induced pulmonary fibrosis in Wistar albino rats. Assigned into 4 groups were 32 Wistar albino rats, comprising the control group (administered 0.9% isotonic saline), BLM group (treated with BLM at a dose of 2.5 mg/kg), BLM+Theo group (treated with Theo at a dose of 75 mg/kg + BLM at a dose of 2.5 mg/kg), and Theo group (treated with Theo at a dose of 75 mg/kg). In the BLM group, a significant decrease was observed in the catalase and glutathione peroxidase enzyme activities, and reduced glutathione (GSH) (p < 0.05, p< 0.05, p< 0.001, respectively), while the malondialdehyde (MDA) levels (p< 0.001) were significantly elevated when compared to the control group. However, the MDA levels in the BLM+Theo group were also significantly higher than in the control group (p< 0.01). Similarly, the GSH levels were significantly higher in the BLM+Theo group than in the BLM group (p< 0.05). The results indicated that Theo reduced the BLM-induced activation of nuclear factor-kappaB (NF-κB) and decreased interleukin-6 (IL-6) levels, together with significant amelioration of the immunohistochemical and histopathological architecture in the lung tissues. It was concluded that the administration of Theo had a positive effect on the GSH level, and activation of NF-κB and IL-6 expression, which were significant proinflammatory markers in the BLM-treated rats.