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Cafeteria diet can cause systemic inflammation and oxidative damage in the various tissues
(Ios Press, 2024) Tursun, Serkan; Şahin, Yaşar; Alcigir, Mehmet Eray; Çınar, Miyase; Karahan, İrfan
BACKGROUND: Cafeteria diet (CAF) is a succesful tool for establishing animal obesity model. This study purposed to show immunoexpression and oxidant-antioxidant status in the various organ tissues of Wistar rats fed CAF. METHODS: Two groups (six rats per group) of Wistar albino rats were fed CAF and standard chow (control) diets for eight weeks. After experimental procedure, the animals were sacrificed. Intestine, stomach, liver, kidney, spleen, heart, lung, and pancreas tissues were sent to Pathology Department and inducible nitric oxide synthase (iNOS), nuclear factor-kappa B (NF-kappa B) and cannabinoid receptor-1 (CB-1) immunoexpressions were assessed. Also, plasma liver function tests and lipid levels were measured total oxidant capacity (TOC) and total antioxidant capacity (TAC) were evaluated in both plasma and liver tissue. RESULTS: The immunoexpressions of NF-kappa B, iNOS and CB-1 were higher in the experiment group for all tissues. TOC was significantly higher in the experiment group, for both plasma and liver tissue (p < 0.001 and p = 0.02). TAC was higher in the experiment group's plasma measurement (p = 0.02), while there was no difference in the liver tissue between experiment and control groups (p = 0.11). CONCLUSION: CAF-induced obesity may be related to increased immunoexpression and oxidative damage in the various organs. Systemic problems should be considered and these phenomenon should be studied more comprehensively.
Clindamycin phosphate and bone morphogenetic protein-7 loaded combined nanoparticle-graft and nanoparticle-film formulations for alveolar bone regeneration – An in vitro and in vivo evaluation
(Elsevier B.V., 2023) Ilhan, Miray; Kilicarslan, Muge; Alcigir, Mehmet Eray; Bagis, Nilsun; Ekim, Okan; Orhan, Kaan
Commonly utilized techniques for healing alveolar bone destruction such as the use of growth factors, suffering from short half-life, application difficulties, and the ability to achieve bioactivity only in the presence of high doses of growth factor. The sustained release of growth factors through a scaffold-based delivery system offers a promising and innovative tool in dentistry. Furthermore, it is suggested to guide the host response by using antimicrobials together with growth factors to prevent recovery and achieve ideal regeneration. Herein, the aim was to prepare and an in vitro - in vivo evaluation of bone morphogenetic protein 7 (BMP-7) and clindamycin phosphate (CDP) loaded polymeric nanoparticles, and their loading into the alginate-chitosan polyelectrolyte complex film or alloplastic graft to accelerate hard tissue regeneration. PLGA nanoparticles containing CDP and BMP-7, separately or together, were prepared using the double emulsion solvent evaporation technique. Through in vitro assays, it was revealed that spherical particles were homogeneously distributed in the combination formulations, and sustained release could be achieved for >12 weeks with all formulations. Also, results from the micro-CT and histopathological analyses indicated that CDP and BMP-7 loaded nanoparticle-film formulations were more effective in treatment than the nanoparticle loaded grafts. © 2023 Elsevier B.V.
Clindamycin phosphate and bone morphogenetic protein-7 loaded combined nanoparticle-graft and nanoparticle-film formulations for alveolar bone regeneration-An in vitro and in vivo evaluation
(Elsevier, 2023) Ilhan, Miray; Kilicarslan, Muge; Alcigir, Mehmet Eray; Bagis, Nilsun; Ekim, Okan; Orhan, Kaan
Commonly utilized techniques for healing alveolar bone destruction such as the use of growth factors, suffering from short half-life, application difficulties, and the ability to achieve bioactivity only in the presence of high doses of growth factor. The sustained release of growth factors through a scaffold-based delivery system offers a promising and innovative tool in dentistry. Furthermore, it is suggested to guide the host response by using antimicrobials together with growth factors to prevent recovery and achieve ideal regeneration. Herein, the aim was to prepare and an in vitro -in vivo evaluation of bone morphogenetic protein 7 (BMP-7) and clindamycin phosphate (CDP) loaded polymeric nanoparticles, and their loading into the alginate-chitosan polyelectrolyte complex film or alloplastic graft to accelerate hard tissue regeneration. PLGA nanoparticles containing CDP and BMP-7, separately or together, were prepared using the double emulsion solvent evaporation technique. Through in vitro assays, it was revealed that spherical particles were homogeneously distributed in the combination formulations, and sustained release could be achieved for >12 weeks with all formulations. Also, results from the micro-CT and histopathological analyses indicated that CDP and BMP-7 loaded nanoparticle-film formulations were more effective in treatment than the nanoparticle loaded grafts.
Clinicopathological and immunohistochemical evaluation of lonidamine-entrapped lipid-polymer hybrid nanoparticles in treatment of benign prostatic hyperplasia: An experimental rat model
(ELSEVIER, 2020) Sengel-Turk, Ceyda Tuba; Alcigir, Mehmet Eray; Ekim, Okan; Bakar-Ates, Filiz; Hascicek, Canan
Benign prostatic hyperplasia (BPH) is a progressive proliferative disease, the incidence of which is constantly increasing due to aging of population. In this research, a hexokinase-II enzyme inhibiting agent, lonidamine - the use of which is limited in BPH treatment due to high hepatic toxicity observed after three months of treatment - was selected as an active agent, based on its mechanism of action in treating BPH. The aim of this study was to evaluate in vivo therapeutic efficacy and hepatic toxicity of lipid-polymer hybrid nanoparticles of lonidamine in a rat BPH model created in rat prostates. After local injections of hybrid nanoparticles of lonidamine were administered to the rat prostates, hyperplasic structures of prostates were evaluated in terms of prostatic index values, immunohistochemical evaluations, and histopathological findings. Liver blood enzyme values were also determined to specify hepatic toxicity. Apoptosis was evaluated by terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) reaction and histopathological methods to determine intravital degenerative destruction in liver. Through this study, lonidamine-loaded hybrid nanoparticles were found to reduce the he-patic toxicity and increase therapeutic efficiency of lonidamine. Therefore, lonidamine-entrapped hybrid nanoparticles may provide a promising, and very safe, drug delivery strategy in the treatment of BPH.
Clinicopathological Evaluation of Clear Cell Hidradenoma (Acrospiroma) Within Multiple Tumor Complex in a Dog
(Univ Fed Rio Grande Do Sul, 2018) Alcigir, Mehmet Eray; Kutlu, Tuncer; Ergin, Irem; Sonmez, Gonca
Background: Clear cell hidradenoma (acrospiroma) is adnexal tumors that arise from the distal excretory duct of eccrine sweat glands. It is generally defined in humanbeings. It presents solitary structure in firmness nodule. Most frequently are encountered in head, face, and upper extremities in humans. Hidradenomas are called generally by definition benign. Their malignant transformations and metastasis are seen very rarely. In veterinary literature database, the malignant form of tumor has been defined as an unique report in four dogs. They are extremely rare tumors in dogs. It is not documented within multiple tumor complex up to now. Case: In the case, three tumors were detected in a 9-year-old neutered female German shepherd dog. After clinical examination, a complete surgical resection of all masses was performed and masses were sent to Pathology for diagnosis. A mass on the right last rib was a 8x6 cm in diameters with severe ulceration. The mass had a hard texture, immobility and irregular borders. Other masses were localized on the back and left caudo-abdominal manunary lobe. Tumors on the back and the mammary lobe did not invade muscle layer, but the tumor on the last rib aggressively invaded surrounding tissue and were very difficult to remove surgically After macroscopy, all the masses were stained with hematoxylin-eosin (I I&E), Mayer's mucicarmine and Periodic Acid Shiff (PAS) stainings. In the first mass, there were multilobular epithelial islands between prominent fibrous septa from the upper to deep of dermis. The neoplastic cells were generally round or polyhedral in shape. Some of cytoplasms were eosinophilic at different degree. But cytoplasms were generally finely granular and vesicular or clear in appearance. Some cells had possible glycogen deposits. Nucleus was oval to round and had fine reticular chromatin and a distinct nucleolus. The tumor was diagnosed as clear cell hidradenoma. Others were was belonged to hemangioma on the back and malignant mixed tumor in the mammary gland. Discussion: In our case, two cell types having benign characteristics were also noted. Some clear cells contained PAS (+) material showing glycogen deposits. Additionally, there were some fibrous septa separating those cell islands. Thus, it is thought that the histopathology shows parallelism to many reports described in human beigns. Clear cell hidradenoma described in this case is first documentation as benign counterpart on the basis of veterinary literatures even though a previous report including clear cell hidradenocarcinoma in four dogs. And also, it has been reported to be very rarely seen tumor in human beings. However, any hormonies in terms of its predilection site can not be found among the cases with clear cell hidradenoma in human counterparts, because the tumor is encountered at skin of last right rib. This situation has shown us the tumor does not select any predilection site as described in this case. It has been understood on the basis of literatures that this is the first case report of describing benign tumor of ecrine sweat duct in dogs. Also, there has been no any documentation regarding in this multiple tumor complex.
A Comparative Pathomorphological Findings Between Leiurus abdullahbayrami and Androctonus crassicauda (Scorpion: Buthidae) Envenomation in Rabbit Animal Model
(Iranian Scientific Society Medical Entomology, 2019) Ozkan, Ozcan; Alcigir, Mehmet Eray
Background: The aim of study was to compare macroscopical and histopathological findings between venoms belonging to two scorpion species, Androdoctonus crassicauda, and the newly discovered Leirus abdullahbayrami. Methods: The animals used in this experimental study were fifteen New Zealand bred rabbits. Three groups were constituted as group I (L. abdullahbayrami group, n= 6), group II (A. crassicauda group, n= 6) and group III (control group, n= 3). The animals in the L. abdullahbayrami group and the A. crassicauda group were envenomed through an intravenous route. The rabbits were monitored for the first 24h following the envenomation. The animals dead within that time period were examined and all animals were sacrificed and standard necropsy process was performed at 24h. Results: The pathomorphological findings from group I were found to be more severe than those observed in group II. The venom from the newly identified L. abdullahbayrami has a greater effect than the venom from the A. crassicauda. Moreover, as this was a rabbit modeling study, the L. abdullahbayrami might pose the most serious health threat to infants in particular due to their smaller body weight. Conclusion: These findings will provide a better understanding of envenomation of human beings in terms of the possible consequences of scorpion toxication on the organs.
Encephalitozoonosis infection in a traditional rabbit farm with neurological manifestations
(Elsevier Science Bv, 2018) Ozkan, Ozcan; Alcigir, Mehmet Eray
Encephalitozoon cuniculi, a zoonotic and opportunistic pathogen, can cause latent infection, especially in lagomorphs. Nowadays, this member of the Eukaryotes has drawn significant attention in the fields of veterinary and public health. The purpose of this study was to determine the seroprevalence of infection in a New Zealand rabbit farm that has a clinical history of neurological manifestations including head tilt ataxia, aggressiveness, seizures, and circling and rotational movements around the body length axis, but the general conditions and food intake were normal. Blood samples were taken from 42 breeding rabbits and researched for E. cuniculi anti-bodies. Out of that, 25 (59%) animals resulted positive against the pathogen. The rabbit was found to be sero-positive for E. cuniculi antibodies, but negative for Toxoplasma gondii and Listeria monocytogenes antibodies. Hematological and serum biochemical parameters were measured at reference intervals. No brain tissue impairment was observed the computed tomography (CT) scan. As a result of these histopathological findings, the brain cortex presented severe neuronal degeneration and partial myelin loss, with reactive diffuse gliosis against the parasite spores was observed to the histopathology. These results are possibly related to the early stage of infection because the parasitic infestation comprise long time spreading. E. cuniculi DNA was detected on brain tissues using polymerase chain reaction (PCR), and it partial DNA sequence was identified as E. cuniculi genotype I.
Evaluation of Burn Wound Healing Efficacy and Biocompatibility of Centella asiatica Mediated Synthesised AgNPs Loaded Hybrid Nanofiber Scaffold: In Vitro and In Vivo Studies
(Wiley-V C H Verlag Gmbh, 2024) Bozkaya, Ogun; Bozkaya, Esra; Ekici, Husamettin; Alcigir, Mehmet Eray; Sahin, Yasar; Cerci, Nebahat Aytuna; Karahan, Siyami
The aim of this study is to evaluate the cell responses, potential skin reactions during the treatment process and burn wound healing efficacy of electrospun polycaprolactone/polyethylene oxide (PCL/PEO) nanofibers (NFs) containing Centella asiatica mediated synthesized silver nanoparticles (CA-AgNPs) by in vitro and in vivo studies. Apoptosis-necrosis, genotoxicity, hemolysis, and cell attachment studies are carried out within the scope of in vitro tests, and irritation, sensitivity, and burn wound studies are carried out within the scope of in vivo tests. The apoptotic index value of CA-AgNPs-[PCL/PEO] NFs material on L929 fibroblast cells is determined as 5.0 +/- 1.0% at the highest concentration and the necrotic index value is 5.0 +/- 0.3%. Micronucleus rates (%) of NFs treated with CHO (Chinese Hamster Ovary) cells are not at genotoxic level. The hemolytic index value of NFs dressing is determined as 0.23 +/- 0.03%, The primary irritation index (PII) value of NFs wound dressing is calculated as 0.36 by irritation tests. In addition, the potential sensitization reaction of NFs extract on guinea pigs is evaluated and the sensitization score is determined as 0.9. The healing efficacy of NFs material on second-degree burn wounds compared to a commercial product is supported by pathomorphological findings.
Evaluation of the combined effects of Turkish mad honey and 5-Fluorouracil in colon cancer model in rats
(Ankara Univ, 2023) Kurtdede, Efe; Alcigir, Mehmet Eray; Alperen, Ahmet Mahmut; Baran, Berk; Karaca, Oğuz Kaan; Gülendağ, Erman
It was aimed to evaluate the regressive effect of grayanotoxin-rich Turkish mad honey and 5-fluorouracil (5-FU), separately and together by using the Nmethyl-N-nitrosourea (MNU)-induced colon cancer modelling in rats. Study groups were designed as control group (CG), cancer control group (CCG), 5Flourouracil group (FUG), Turkish mad honey group (HG), Turkish mad honey and 5-FU combined group (FU-HG). White blood cell (WBC), lymphocyte, eosinophil, basophil, serum lactate dehydrogenase (LDH), total oxidant status (TOS), and total protein values of the rats in the CCG were significantly lower than the values of the rats in the CG, whereas serum Bcl-2 and survivin levels were significantly higher in the rates belonged to the CCG in comparison to those in the CG. The presence of anaplastic epithelial cells, vascularization, precancerous changes, and inflammatory infiltration detected in the colon and small intestine of the rats in FU-HG, FUG, HG were less intense (P<0.05) compared to the findings in the rats in CCG. In conclusion, mad honey and 5 FU reduced anaplastic cell growth and oxidative stress via suppressed antiapoptotic activity. Considering the histopathological findings in the liver and kidney, no toxicity occurred related to mad honey and 5-FU metabolization. Therefore, the combined use of these two substances may be an alternative method in the treatment of colon cancer.
First detection and molecular characterisation of a pigeon aviadenovirus A and pigeon circovirus co-infection associated with Young Pigeon Disease Syndrome (YPDS) in Turkish pigeons (Columba livia domestica)
(Wiley, 2022) Sahindokuyucu, Ismail; Turkmen, Merve Biskin; Sumer, Tugce; Elhag, Ahmed Eisa; Alcigir, Mehmet Eray; Yazici, Zafer; Barry, Gerald
Pigeon aviadenovirus A and Pigeon circovirus are both DNA viruses, infect and cause severe clinical diseases in pigeons. These viruses are associated with an immunosuppression syndrome similar to 'Young Pigeon Disease Syndrome' (YPDS). This study reports the identification of a natural co-infection, with severe clinical signs (crop vomiting, watery diarrhoea, anorexia and sudden death) of Pigeon aviadenovirus A and Pigeon circovirus in a breeding pigeon flock in Central Anatolia, Turkey. Both viruses were isolated from pigeons pooled internal organs using primary chicken embryo kidney cell cultures (CEKC) and specific pathogen-free (SPF) embryonated chicken eggs. Also, both viruses were identified by PCR amplification followed by Sanger sequencing whereas histopathological examination showed degenerated hepatocytes with basophilic intranuclear viral inclusions. As known, both viruses typically have similar transmission characteristics and common clinical manifestations; however, co-infection may exacerbate the disease with devastating outcomes. This is the first report of its kind in Turkey for those viruses and is essential for the protection against these kinds of infections in pigeons.
The First Molecular Detection and Genotyping of Encephalitozoon cuniculi in Rabbit's Eye in Turkey
(Kafkas Univ, Veteriner Fakultesi Dergisi, 2018) Ozkan, Ozcan; Karagoz, Alper; Kocak, Nadir; Alcigir, Mehmet Eray
Encephalitozoon cuniculi was first recognized as the disease agent in rabbits in 1922. The genotype of E. cuniculi isolated from laboratory rabbits with the neurologic disease was described as genotype I. In the eye, this parasite causes damage to the lens, causing phacoclastic uveitis and cataracts. Intraocular infection often occurs in cases of transplacental transmission. There has been no report on the molecular diagnosis of the parasite in Turkey. The current study is the first report on the detection of E. cuniculi spores using the molecular method in Turkey. In our previous study, a rabbit breeding facility was determined seropositive for E. cuniculi infection monitored for five years in terms of clinical symptoms. An autopsy was performed for a definite diagnosis of the infection. Samples were stained according to the hematoxylin-eosin (H&E) staining after tissue processing procedure and histopathologic analysis was performed. In addition to, the samples for DNA extraction were also taken during the autopsy. ECUNF and ECUNR species-specific primer pairs were used for amplification and genotyping of E. cuniculi. The animals were observed no clinical symptoms except ocular lesion (n=9). Therefore, one of these rabbits was used in the autopsy to definite diagnosis and determination of the damage to the eye. As histopathological, the lesions in the eye were found in the initial or middle stage of progressive infection. The DNA sequence showed that E. cuniculi examined in the present study were genotype I. Possible cause of the visible white mass in the rabbit's eye may be the parasite infection. Therefore, clinicians may consider E. cuniculi as one of the possible causes of ocular lesions in rabbits during daily inspection or ophthalmological examination.
High-fructose consumption suppresses insulin signaling pathway accompanied by activation of macrophage and apoptotic markers in rat testis
(Elsevier, 2023) Yildirim, Onur Gokhan; Guney, Ceren; Alcigir, Mehmet Eray; Akar, Fatma
Dietary high-fructose may cause metabolic disturbances; however, its effect on the reproductive system is little understood. The insulin signaling pathway is critical in testicular development, maintenance of microcirculation and spermatogenesis. Therefore, in this study, we aimed to investigate the impact of dietary high-fructose on insulin signaling pathway as well as macrophage and apoptotic markers in testicular tissue of rats. Fructose was administered to male Wistar rats as a 20% solution in drinking water for fifteen-week. Gene expression of ir-beta, irs-1, irs-2, pi3k, akt, mtor, and enos in the testicular samples was determined by real-time PCR. Protein expression of IR, IRS-1, IRS-2, PI3K, Akt, phospho-Akt (p-Akt), mTOR, eNOS, phospho-eNOS (p-eNOS), and GLUT5 was established by analysis of Western Blot. Testicular expression of occludin, CD163, CD68, caspase-8, and caspase-3 was analyzed by using immunohistochemical assay. Testicular level of fructose was measured by colorimetric method. Dietary high-fructose decreased mRNA expressions of irs-1, irs-2, pi3k, and mtor in the testicular tissue of rats. Also, this dietary intervention impaired protein expressions of IR, IRS-1, IRS-2, PI3K, p-Akt, mTOR, eNOS, and p-eNOS as well as p-Akt/Akt and p-eNOS/eNOS ratios in the testis of rats. However, a high-fructose diet increased the expression of CD163, CD68, caspase-8 and caspase-3, but decreased that of occludin, in the testicular tissue of rats. The high-fructose consumption in rats suppresses testicular insulin signaling but activates macrophages-related factors and apoptotic markers. These changes induced by dietary fructose could be related to male reproductive dysfunction.
An Investigation of the Effects of Curcumin on the Changes in the Central Nervous System of Rats Exposed to Aroclor 1254 in the Prenatal Period
(Bentham Science Publ, 2018) Alcigir, Mehmet Eray; Dogan, Halef Okan; Dikmen, Begum Yurdakok; Dogan, Kubra; Vural, Sevil Atalay; Yilmaz, Fatma Meric; Isgoren, Atilla
Background & Objective: Aroclor 1254 is a widespread toxic compound of Polychlorinated Biphenyls (PCBs), which can create significant nervous problems. No remedies have been found to date. The aim of this study was to reveal the damage that occurs in the central nervous system of rat pups exposed to Aroclor 1254 in the prenatal period and to show the inhibiting effect of curcumin, which is a strong anti-oxidant and neuroprotective substance. Method: The study established 3 groups of adult female and male Wistar albino rats. The rats were mated within these groups and the offspring rats were evaluated within the group given Aroclor 1254 only (n=10) and the group was given both Aroclor 1254 and curcumin (n=10) and the control group (n=10). The groups were compared in respect of pathomorphological damage. The immunohistochemical evaluation was made of 8-hydroxdeoxyguanosine (8-OHdG), 4-hydroxynoneal (4HNE), myelin basic protein (MBP) expressions and TUNEL reaction. The biochemical evaluation was made of the changes in the TAS-TOS and Neuron Specific Enolase (NSE) levels. Damage was seen to have been reduced with curcumin in the 8OHdG and TUNEL reactions, especially in the forebrain and the midbrain, although the dosage applied did not significantly change TAS and TOS levels. Consequently, it was understood that Aroclor 1254 caused damage in the central nervous system of the pup in the prenatal period, and curcumin reduced these negative effects, particularly in the forebrain and the midbrain. Conclusion: It was concluded that curcumin could be a potential neuroprotective agent and would be more effective at higher doses.
Lactobacillus plantarum improves lipogenesis and IRS-1/AKT/eNOS signalling pathway in the liver of high-fructose-fed rats
(TAYLOR & FRANCIS LTD, 2020) Sumlu, Esra; Bostanci, Aykut; Sadi, Gokhan; Alcigir, Mehmet Eray; Akar, Fatma
In the present study, we investigated the influence of Lactobacillus plantarum and Lactobacillus helveticus supplementation on lipogenesis, insulin signalling and glucose transporters in liver of high-fructose-fed rats. Fructose was given to the rats as a 20% solution in drinking water for 15 weeks. Lactobacillus plantarum and L. helveticus supplementations were performed by gastric gavage once a day during final 6 weeks. Dietary high-fructose increased hepatic weight, lipid accumulation and FASN expression as well as caused a significant reduction in IRS-1 expression, pAKT/total AKT and peNOS/total eNOS ratios, but an elevation in GLUT2 and GLUT5 mRNAs in the liver. Lactobacillus plantarum supplementation decreased hepatic weight, triglyceride content and FASN expression as well as improved IRS-1/AKT/eNOS pathway and GLUT2 expression in the liver of high-fructose-fed rats. However, L. helveticus supplementation exerted a restoring effect on lipid accumulation by decreasing FASN expression, and regulating effect on IRS-1 and GLUT2 expressions.
Necroptosis mediated by receptor interacting protein kinase 3 as critical players in experimental congenital hypothyroidism related neuronal damage
(Kare Publ, 2021) Duman, Gulhan; Alcigir, Mehmet Eray; Yavuz, Hayrettin
OBJECTIVE: Congenital hypothyroidism (CH) is literally described as congenital thyroid hormone imperfection. The primary objective of this research was to reveal the possible relation between receptor-acting protein kinase 3 (RIPK3) activity and neuronal damages in rat pups with CH. In addition, we evaluated the favorable impacts of 3.6-dibromo-alpha-([phenylamino] methyl)-9H-carbazole-9-ethanol (P7C3) reducing RIPK3 activity. METHODS: Adult rats were accordingly assigned into four groups: Group 1, which is called congenital hypothyroid; Group 2, which is called congenital hypothyroid administered P7C3; Group 3, called CH administered P7C3 and L-thyroxine; and Group 4, control group. RIPK3 level in plasma concentration and its expression in tissue was determined in all groups. RESULTS: Increased RIPK3 expressions were detected as high in the CH group when it is compared to the control group. Furthermore; the expressions in neuronal cytoplasm were found similar among Groups II and III. RIPK3 expressions in those two groups were relatively higher than in the control group. Most reacted parts of the brain were especially Purkinje cells in the cerebellum. CONCLUSION: It is concluded that there is excellent parallelism among damaged neurons and high RIPK3 activity in CH pathogenesis. P7C3 compounds may have a safeguarding impact on CH due to decreasing RIPK3 activity.
Ocular pharmacokinetics and toxicity of nanoparticular acetazolamide: In vivo distribution and safety of PHBV-ACZ nanoparticle
(Elsevier, 2023) Erdal, Ebru; Bakici, Caner; Arslan, Aslihan; Batur, Baris; Yaman, Mehmet Emrah; Alcigir, Mehmet Eray; Akyol, Mesut
Diabetic macular edema (DME) is defined as fluid accumulation in the macular region, between the retinal layers, due to many diseases, especially diabetes. DME is one of the major complications of diabetic retinopathy (DRP). Carbonic anhydrase inhibitors (CAI) are a pharmaceutical agent used in different fields, especially glaucoma treatment. Acetazolamide (ACZ), which is a CAI, is an active substance that has been used off-label for many years in the treatment of macular edema due to diabetes and many other diseases. The low solubility and bioavailability of ACZ limit its use in the treatment of DME. In this study, a nanoparticulate formulation was developed that would increase the solubility and bioavailability of ACZ and allow it to be administered intravitreally. ACZ was loaded on poly(3-hydroxybutyrate-co-3-Hydroxyvalerate) (PHBV) nanoparticles and the loading efficiency was 71.58 +/- 1.22%. Toxicity of nanoparticles after intravitreal application was evaluated with anterior segment and posterior segment examination findings, intraocular pressure (IOP) measurements and electrophysiological tests. At the end of the 3-month follow-up, electroretinography (ERG) measurements demonstrated that ACZ loaded PHBV (PHBV-ACZ) nanoparticles did not cause loss of function in retinal cells. On histological examination, rare degenerative changes were observed in several cell groups. In addition, pharmacokinetic studies were performed to determine the tissue distribution of ACZ at various periods. ACZ was identified in vitreous humor and retina at the highest concentration. Based on our results, the prepared nanoparticle formulation can release long-term CAI for DRP therapy and accordingly can reduce the need for monthly intravitreal injections.
Potential mechanistic pathways underlying intestinal and hepatic effects of kefir in high-fructose-fed rats
(Elsevier, 2021) Akar, Fatma; Sumlu, Esra; Alcigir, Mehmet Eray; Bostanci, Aykut; Sadi, Gokhan
Excess intake of fructose may contribute to the high prevalence of metabolic disorder. In this study, we investigated the effects of kefir supplementation on the intestine-liver-adipose tissue axis in metabolic disorder induced by high-fructose diet in rats to describe mechanistic action and potential therapeutic value of kefir. Fructose was given to the rats as a 20% solution in drinking water for 15 weeks. Kefir was administrated by gastric gavage once a day during the final six weeks. Kefir supplementation improved metabolic parameters, including plasma triglyceride and insulin levels; hepatic weight, triglyceride content and fatty degeneration; omental fat mass in fructose-fed rats. Kefir supplementation decreased the ratio of Firmicutes/Bacteroidetes in feces, as well as necrotic degeneration, expression levels of nuclear factor-kappa B (NF-kappa B), and inducible nitric oxide synthase (iNOS), but increased expression of tight-junction proteins occludin and claudin-1, in the ileum of the fructose-fed rats. Kefir treatment also reduced the mRNA levels of key lipogenic genes sterol regulatory element-binding protein (SREBP-1c) and fatty acid synthase (FASN) together with a decline in expression of tumor necrosis factor-alpha (TNF-alpha), NF-kappa B, and glycosylated glycoprotein (CD68) in the liver. Moreover, kefir treatment improved insulin signaling at the level of insulin receptor substrate 1 (IRS-1) and phospho-endothelial nitric oxide synthase (peNOS) as well as fructose transporters (GLUT2 and GLUT5) in the liver, but not in the adipose tissue, of high-fructose-fed rats. Consequently, kefir supplementation suppresses hepatic lipogenesis and inflammatory status, but promotes insulin signaling, in association with a change of the fecal microbiota and attenuation of the intestinal permeability factors in high-fructose-fed rats. Thus, we propose that kefir has favorable effects on the hepatic and intestinal irregularities induced by fructose overconsumption.
Preventive and therapeutic effects of the peel powder of P. granatum in a rat sepsis model
(Univ Zagreb Vet Faculty, 2023) Ulker, Ufuk; Demirel, Murside Ayse; Bayraktar, Bulent; Alcigir, Mehmet Eray; Aksoy, Adil
The aim of the present study was to evaluate the treatment potential of Punica granatum L. peel powder in an experimentally induced sepsis model in rats. Sepsis was induced in 10-week-old, male, Wistar Albino (n=24) rats. The animals were divided into four groups: Sham-operated (S) Group, Control (C) Group, Treatment-1 (T1) Group, and Treatment-2 (T2) Group. To induce the sepsis model, the cecal ligation and puncture procedure was performed. The P. granatum peel powder (200 mg/kg; per os) was applied one hour before (T1) and 10 hours after (T2) surgery in a volume of 2 mL. At the end of the experimental procedure, microbial and histopathological analyses were performed. The histopathological scores on the liver, lungs, heart, kidney, spleen, and pancreas were evaluated. Escherichia coli, Staphylococcus aureus and E. coli + S. aureus were isolated from blood cultures. Severe bacteria were detected in the blood of the group C animals. It was found that there were fewer bacteria in groups T1 (n=2) and T2 (n=4) compared with group C. There were no lesions in the pancreas tissues of any groups. Vascular changes, degeneration, and necrosis were common in the organs in all cases of group C compared to group S. The findings in group T1 were similar to those in group C, however, it was seen in fewer animals. It was determined that there was a general improvement in group T2, and in addition the existing lesions were moderate in severity. In conclusion, P. granatum L. peel powder prevented CLP-induced lung injury in experimental rats. Thus, P. granatum L. peel powder may be an alternative therapeutic agent against lung tissue injury induced by sepsis. The recovery from inflammation was better in group T2 than in the other groups. According to the results of the current study, P. granatum peel powder was found to be effective in the treatment of sepsis with antimicrobial and anti-inflammatory functions.
Relationship between seropositivity of Encephalitozoon cuniculi and renal biochemical markers in clinically healthy rabbits
(Ankara Univ Press, 2019) Ozkan, Ozcan; Yucesan, Banucicek; Pekkaya, Selcuk; Alcigir, Mehmet Eray; Gurcan, Ismayil Safa
Encephalitozoon cuniculi can cause latent disease, especially in lagomorphs and many wild and domestic animals in various countries. This infection is important for veterinary and public health because it is caused by a potentially zoonotic and opportunistic pathogen. The aim of this study was to investigate the relationship between seropositivity of E. cuniculi and renal function markers, which may be useful in predicting the disease in clinically healthy rabbits. In this study, the seropositivity of E. cuniculi infection in clinically healthy rabbits was determined, and necropsy fmdings were evaluated along with the results of renal function tests. In a laboratory rabbit breeding facility, enzyme-linked immunosorbent assay (ELISA) tests showed that 48 (49.5%) of 97 rabbits were seropositive against E. cuniculi. Blood urea nitrogen (BUN) and creatinine levels were significantly elevated in seropositive animals. Two seropositive rabbits were necropsied to confirm the infection. According to histopathological findings in the kidney, degenerative changes and E. cuniculi spores were identified in the tubule epithelia. Serum creatinine (p<0.001) and BUN (p<0.01) levels were found to have a statistically significant relationship with the serological status of rabbits. Serological and histopathological methods are not routinely used in rabbits to diagnose E. cuniculi infection. The kidneys were one of the most affected organs in encephalitozoonosis in rabbits. As revealed in this study, the testing blood urea nitrogen and creatinine levels would be useful for the evaluation of general health status and renal function of the seropositive rabbits, and clinical interpretation as well.
Subacute Stage of Encephalitozoon cuniculi Infection in Eye Lesions of Rabbit in Turkey
(Iranian Scientific Society Medical Entomology, 2018) Ozkan, Ozcan; Alcigir, Mehmet Eray
Background: Encephalitozoon cuniculi is an opportunistic microsporidian parasite that can affect a number of different species of mammalian animals and humans. The parasite can pose also threat for rabbits even though it causes several sporadic and asymptomatic infections. Infection of eyes is common and clinical symptom of ocular infection may include uveitis and cataracts. We found out subacute findings in naturally infected animals and show here a first described eye lesions as well as central nervous system and kidneys in Turkey. Methods: The rabbits (n: 171) of breeding units were observed to daily clinical examination for infection of E. cuniculi during three years. The eyes of five rabbits (2.9%) showed white intraocular masses or cataracts in the breeding units during daily examinations. The infection was described clinicopathologically in collected organ samples in the animals. During observation, macroscopically, corneal lesions and opacity and impaired lens were taken into attention as well as hyperemia in central nervous system and kidney. Histopathologically, parasitophorous vacuoles pertaining to E. cuniculi were detected in all three tissues during different routine Haematoxylin-Eosin and Gram stainings. Results: Degenerative and necrotic changes in epithelium of cornea and lens and also neurons and tubules were predominantly observed in addition to nonpurulent interstitiel nephritis and encephalitis. Conclusion: The results from study lead to subacute findings especially in eye during natural E. cuniculi infections following asymptomatic and latent changes among breeding colony. The lesions indicated sub-acute stage of E. cuniculi infection in eye lesions of rabbit in Turkey.

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