Klinik Öncesi Bilimleri Bölümü Makale Koleksiyonu

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https://hdl.handle.net/20.500.12418/248

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The Effects of Sunitinib in Healthy and Cisplatin-Induced Rats
(04.01.2023) Demirtaş, Levent; Gürbüzel, Mehmet; Akbaş, Emin Murat; Tahirler, Hilal; Karataş, Özhan; Arslan, Yusuf Kemal
Sunitinib is a multitargeted kinase inhibitor that inhibits many receptor tyrosine kinases and has been used in the treatment of gastrointestinal stromal tumors, metastatic renal cell carcinoma, and pancreatic neuroendocrine tumors. In this study, the effects of sunitinib given to rats, both alone and after stress with cisplatin, were investigated. The animals were divided into four groups – (1) control group (C) administered interperitoneally with a single dose 0.9% saline, (2) Cis group administered a single dose (7 mg/kg) of cisplatin, (3) Sun group administered 10 mg/kg sunitinib for seven days, and (4) Cis+Sun group administered 10 mg/kg sunitinib for seven days after a single dose (7 mg/kg) of cisplatin. After these applications, the rats were sacrificed, and blood and tissue samples were taken for biochemical and histopathological evaluations. Sunitinib did not show any effect on urea, creatine, and kidney IL1β and TGF-β3 expression levels when administered alone; it increased ALT, AST, and IL-38 levels. When sunitinib was given to the cisplatin-induced rats, it was observed that the increase in ALT, AST, and IL-38 levels increased more than the rats that was given only sunitinib. According to the data obtained, sunitinib does not cause a significant change in kidney tissue under both normal and stress conditions, while it creates stress in liver tissue. In addition, its toxicity in the liver becomes more certain as a result of its combination with cisplatin.
Mechanism of anticancer effect of gambogic acid on gastric signet ring cell carcinoma
(16.08.2023) Joha, Ziad; Öztürk Ayşegül; Yulak Fatih; Karataş, Özhan; Ataseven Hilmi
Gambogic acid has demonstrated inhibitory effects on the growth of various cancer cell types, such as breast cancer, pancreatic cancer, prostate cancer, lung cancer, and osteosarcoma. This study aims to investigate the antiproliferative activity of Gambogic acid on SNU-16 cells derived from gastric signet ring cell carcinoma and elucidate the underlying mechanisms. The cytotoxic effect of gambogic acid was evaluated in SNU-16 cells by treating them with different concentrations of the compound, and the XTT cell viability assay was employed to assess cell viability. ELISA was used to measure bax, BCL- 2, caspase 3, PARP, and 8-oxo-dG levels. Additionally, immunofluorescence staining was applied to assess 8-oxo-dG and LC3β levels in SNU-16 cells. It was observed that gambogic acid exerted a dose-dependent and statistically significant antiproliferative effect on SNU-16 cells. The IC50 value of gambogic acid in SNU-16 cells was found to be 655.1 nM for 24 h. Subsequent investigations conducted using the IC50 dose revealed a significant upregulation of apoptotic proteins including cleaved caspase 3, Bax, and cleaved PARP (p < 0.001), along with a downregulation of BCL-2 (p < 0.001), an anti-apoptotic protein. Moreover, the administration of this drug led to an upregulation of 8-oxo-dG (p < 0.001), a widely acknowledged biomarker indicating oxidative damage in DNA, as well as an increase in LC3β levels (p < 0.05), a marker associated with autophagy. The antiproliferative effect of gambogic acid against gastric signet ring cell carcinoma is attributed to its ability to induce apoptosis and autophagy. This discovery highlights the promising potential of gambogic acid as a treatment option for gastric signet ring cell carcinoma.
The effects of sorafenib in healthy and cisplatin-treated rats
(07.10.2023) Demirtaş, Levent; Gürbüzel, Mehmet; Tahirler, Hilal; Akbaş, Emin Murat; Karataş, Özhan; Arslan, Yusuf Kemal
Background. Sorafenib is a multikinase inhibitor currently used in the treatment of hepatocellular carcinoma, renal cell carcinoma and thyroid cancer. Objectives. The literature on this agent is scarce. This study aimed to evaluate the effects of sorafenib when administered to both healthy and cisplatin-induced rats. Materials and methods. The animals were divided into 4 groups: 1) control group that received 0.9% saline intraperitoneally (C); 2) group administered a single dose (7 mg/kg) of cisplatin (Cis); 3) a group administered 20 mg/kg of sorafenib for 7 days (Sor); 4) group administered 20 mg/kg of sorafenib followed by 7 mg/kg of cisplatin for 7 days (Cis+Sor). All animals were sacrificed 7 days after the completion of their treatment arm, and serum and tissue samples were taken. Results. Alanine aminotransferase (ALT), aspartate aminotransferase (AST) and interleukin 38 (IL-38) levels were increased in the Sor and Cis+Sor groups compared to the control group. When compared with the control group, serum urea, creatinine, kidney IL-1β, and tumor necrosis factor alpha (TNF-α) levels did not change in the Sor group. When compared to the Cis group, the levels of these parameters decreased in the Cis+Sor group. Conclusions. According to the data obtained, sorafenib caused liver toxicity when given to both healthy and cisplatin-induced rats. While sorafenib did not cause any significant changes in the kidneys when given to healthy rats, it had a healing effect in kidneys after stress induced by cisplatin.
FGF-18 alleviates memory impairments and neuropathological changes in a rat model of Alzheimer's disease
(22.07.2023) Çetindağ Çiltaş, Arzuhan; Karabulut Sebahattin; Şahin Bilal; Filiz, Ahmet Kemal; Yulak Fatih; Özkaraca Mustafa; Karataş, Özhan; Çetin, Ali
Alzheimer’s disease (AD) is a multifactorial pathology marked by amyloid beta (Aβ) accumulation, tau hyperphosphorylation, and progressive cognitive decline. Previous studies show that fibroblast growth factor 18 (FGF18) exerts a neuroprotective effect in experimental models of neurodegeneration; however, how it affects AD pathology remains unknown. This study aimed to ascertain the impact of FGF18 on the behavioral and neuropathological changes in the rat model of sporadic AD induced by intracerebroventricular (ICV) injection of streptozotocin (STZ). The rats were treated with FGF18 (0.94 and 1.88 pmol, ICV) on the 15th day after STZ injection. Their cognitive function was assessed in the Morris water maze and passive avoidance tests for 5 days from the 16th to the 21st days. Aβ levels and histological signs of neurotoxicity were detected using the enzymelinked immunosorbent assay (ELISA) assay and histopathological analysis of the brain, respectively. FGF18 mildly ameliorated the STZ-induced cognitive impairment; the Aβ accumulation was reduced; and the neuronal damage including pyknosis and apoptosis was alleviated in the rat brain. This study highlights the promising therapeutic potential for FGF18 in managing AD.
Anticancer activity of sinapic acid by inducing apoptosis in HT-29 human colon cancer cell line
(28.04.2023) Taştemur, Şeyma; Hacısüleyman, Levent; Karataş, Özhan; Yulak Fatih; Ataseven Hilmi
Colorectal cancer is the third most lethal and fourth most commonly diagnosed cancer worldwide. Sinapic acid, a derivative of hydroxycinnamic acid, is a promising phytochemical exhibiting numerous pharmacological activities in various systems. It is a substantial chain-breaking antioxidant that operates as a radical scavenger. The aim of this research was to investigate the antiproliferative effect of sinapic acid on the HT-29 cell line besides the mechanisms underlying this activity. The effect of sinapic acid on the viability of HT-29 cell line was investigated using XTT assay. The levels of BCL-2, cleaved caspase 3, BAX, cleaved PARP, and 8-oxo-dG were measured using ELISA. Gamma-H2AX and cytochrome c expressions were assessed semiquantitatively using immunofluorescence staining. Sinapic acid at 200 µm and higher doses produced a significant antiproliferative effect on HT-29 cells. The IC50 value was found to be 317.5 µm for 24 h. Sinapic acid (317.5 µm) significantly elevated cleaved caspase 3, BAX, cleaved PARP, and 8-oxo-dG levels. The levels of gamma-H2AX foci are significantly higher, while the levels of cytochrome c are lower in sinapic acid-treated HT-29 cells. These results indicate that sinapic acid has antiproliferative, apoptotic, and genotoxic effects on colon cancer cells.
Prevalence of Shiga Toxin-Producing O157 and Non-O157 Escherichia coli in Anatolian Buffaloes (Bubalus bubalis)
(2023) Kalın, Recep; Moğulkoç, Mahmut Niyazi; Karahan, Murat; Turan, Turhan; Işıdan, Hakan; Berber, Engin
Shiga toxin producing Escherichia coli (STEC) serotypes are recognized as potentially important food-borne pathogens for humans. Ingestion of E. coli contaminated food is largely known to originate from livestock. Cattle and sheep herds hold the majority of agricultural revenue in Turkey but Anatolian water buffaloes have often been underestimated for foodborne pathogens. The aim of this study is to determine virulence genes harboring E. coli O157 and six major non-O157 STEC (O26, O45, O103, O111, O121, and O145) serotypes in feces of healthy Anatolian water buffaloes by using multiplex PCR (mPCR) method. Of the collected 458 fecal samples from healthy live animals, we have performed virulence and serotype targeting mPCR following direct DNA extraction from collected samples. Results indicate that there is 0.9% of O157 prevalence while six major non-O157 E. coli have not been identified. The characterization results of the virulence genes also showed that eae is most prevalent (5.7%) followed by ehxA (3.9%) and stx1 (3.1%). In this study, we have shown Anatolian buffaloes might have a relationship with other O-type E. coli strains. Non-O157 STECs, which are often disregarded in both animals and humans, should be investigated. As a consequence, gaining regional or national data collection will allow to implement better effective diagnosis and treatment options.
The effects of low?level laser therapy on polycystic ovarian syndrome in rats: three diferent dosages
(Ağustos 2023) Polat, Bülent; Okur, Damla Tuğçe; Çolak, Armağan; Yılmaz, Kader; Özkaraca, Mustafa; Çomaklı, Selim
The main objective of this in vivo study was to investigate the efect of diferent low-level laser therapy (LLLT) doses on polycystic ovary syndrome (PCOS). In the present experimental study, a single dosage of estradiol valerate (EV) was administered to induce PCOS in female rats. After administration of the EV for induction of PCOS, rats were divided into 5 groups (n = 8/group): C group (animals that were not exposed to any form of procedure), PC group (no treatment following EV induction), L1 group (1 J/cm2 LLLT treatment following EV induction), L2 group (2 J/cm2 LLLT treatment following EV induction), L3 group (6 J/cm2 LLLT treatment following EV induction). The results indicated that no signifcant dif ference was found in the serum levels of luteinizing hormone (LH), follicle-stimulating hormone (FSH), and progesterone (P4) between the C and L2 groups (p < 0.05). Although the serum levels of testosterone (T) were signifcantly higher in the C group compared with other groups (p < 0.05), the L2 group was determined to be the closest to the C group. Additionally, the LH, FSH, and T receptor level of the L2 group was closest to the C group. In conclusion, a 2 J/cm2 dosage of LLLT (L2 group) can be considered the most potentially efective treatment of PCOS in the rat. However, more studies are needed to determine the optimal dose of LLLT for the treatment of PCOS.
Parthenolide as a potential analgesic in the treatment of paclitaxel?induced neuropathic pain: the rat modeling
(Haziran 2023) Toraman, Emine; Bayram, Cemil; Sezen, Selma; Özkaraca, Mustafa; Hacımüftüoğlu, Ahmet; Budak, Harun
In this study, we determined the therapeutic efect of parthenolide (PTL), the active component of Tanacetum parthenium, on neuropathic pain caused by paclitaxel (PTX), a chemotherapeutic drug frequently used in cancer treatment, at the gene and protein levels. To this end, 6 groups were formed: control, PTX, sham, 1 mg/PTL, 2 mg/kg PTL, and 4 mg/kg PTL. Pain formation was tested by Randall-Selitto analgesiometry and locomotor activity behavioral analysis. Then, PTL treatment was performed for 14 days. After the last dose of PTL was taken, Hcn2, Trpa1, Scn9a, and Kcns1 gene expressions were measured in rat brain (cerebral cortex/CTX) tissues. In addition, changes in the levels of SCN9A and KCNS1 proteins were determined by immunohistochemical analysis. Histopathological hematoxylin-eosin staining was also performed to investigate the efect of PTL in treating tissue damage on neuropathic pain caused by PTX treatment. When the obtained data were analyzed, pain threshold and locomotor activity decreased in PTX and sham groups and increased with PTL treatment. In addition, it was observed that the expression of the Hcn2, Trpa1, and Scn9a genes decreased while the Kcns1 gene expression increased. When protein levels were examined, it was determined that SCN9A protein expression decreased and the KCNS1 protein level increased. It was determined that PTL treatment also improved PTX-induced tissue damage. The results of this study demonstrate that non-opioid PTL is an efective therapeutic agent in the treatment of chemotherapy-induced neuropathic pain, especially when used at a dose of 4 mg/kg acting on sodium and potassium channels
FGF-18 alleviates memory impairments and neuropathological changes in a rat model of Alzheimer’s disease
(Temmuz 2023) Çiltaş, Arzuhan Yeşildağ; Karabulut Sebahattin; Şahin, Bilal; Filiz, Ahmet Kemal; Yulak, Fatih; Özkaraca, Mustafa; Karatas, Özhan; Çetin, Ali
Alzheimer’s disease (AD) is a multifactorial pathology marked by amyloid beta (Aβ) accumulation, tau hyper phosphorylation, and progressive cognitive decline. Previous studies show that fibroblast growth factor 18 (FGF18) exerts a neuroprotective effect in experimental models of neurodegeneration; however, how it affects AD pathology remains unknown. This study aimed to ascertain the impact of FGF18 on the behavioral and neuropathological changes in the rat model of sporadic AD induced by intracerebroventricular (ICV) injection of streptozotocin (STZ). The rats were treated with FGF18 (0.94 and 1.88 pmol, ICV) on the 15th day after STZ injection. Their cognitive function was assessed in the Morris water maze and passive avoidance tests for 5 days from the 16th to the 21st days. Aβ levels and histological signs of neurotoxicity were detected using the enzyme linked immunosorbent assay (ELISA) assay and histopathological analysis of the brain, respectively. FGF18 mildly ameliorated the STZ-induced cognitive impairment; the Aβ accumulation was reduced; and the neuronal damage including pyknosis and apoptosis was alleviated in the rat brain. This study highlights the promising therapeutic potential for FGF18 in managing AD.
Evaluated periodontal tissues and oxidative stress in rats with neuropathic pain-like behavior
(Ekim 2023) Toraman, Ayşe; Toraman, Emine; Özkaraca, Mustafa; Budak, Harun
Background Oxidative stress has a critical effect on both persistent pain states and periodontal disease. Voltage-gated sodium NaV1.7 (SCN9A), and transient receptor potential ankyrin 1 (TRPA1) are pain genes. The goal of this study was to investi gate oxidative stress markers, periodontal status, SCN9A, and TRPA1 channel expression in periodontal tissues of rats with paclitaxel-induced neuropathic pain-like behavior (NPLB). Methods and results Totally 16 male Sprague Dawley rats were used: control (n=8) and paclitaxel-induced pain (PTX) (n=8). The alveolar bone loss and 8-hydroxy-2-deoxyguanosine (8-OHdG) levels were analyzed histometrically and immu nohistochemically. Gingival superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) activities (spectrophotometric assay) were measured. The relative TRPA1 and SCN9A genes expression levels were evaluated using quantitative real-time PCR (qPCR) in the tissues of gingiva and brain. The PTX group had significantly higher alveolar bone loss and 8-OHdG compared to the control. The PTX group had significantly lower gingival SOD, GPx and CAT activity than the control groups. The PTX group had significantly higher relative gene expression of SCN9A (p=0.0002) and TRPA1 (p=0.0002) than the control in gingival tissues. Increased nociceptive susceptibility may affect the increase in oxidative stress and periodontal destruction. Conclusions Chronic pain conditions may increase TRPA1 and SCN9A gene expression in the periodontium. The data of the current study may help develop novel approaches both to maintain periodontal health and alleviate pain in patients suffering from orofacial pain.
Comparison of three different dosages of low-level laser therapy on expression of cell proliferation and inflammatory markers following ovariohysterectomy in rats
(Eylül 2023) Polat, Bülent; Okur, Damla Tuğçe; Çolak, Armağan; Okur, Sıtkıcan; Özkaraca, Mustafa; Yılmaz, Kader
The objective of the current study was to evaluate Low-level laser therapy (LLLT) on the healing of incisional wounds following ovariohysterectomy in rats, by means of subjective histopathological and immunohistochemical analysis. A total of 72 female Wistar rats were categorised into four treatment groups (Group I; sacrification 4hours following only one LLLT application, Group II; sacrification 7days following only one LLLT application, Group III; sacrification 4hours after two LLLT applications, and Group IV; sacrification 7days after two LLLT applications). Each group was further divided into four different doses subgroups (Group Control [C, off mode LLLT application], L1 [1 J/ cm2 ], L3 [3 J/cm2 ], and L6 [6 J/cm2 ]), with equal representation in each subgroup. Ovariohysterectomy was employed using two 2-cm-length midline abdominal incisions in the left and right sides of line alba. The Group C was assigned to the left side incision to each rat in the study. After irradiation, the tissue was subjected to histopathological analysis to determine the extent of mononuclear cell infiltration, edoema, and epithelialization. Additionally, immunohistochemical analysis was performed to evaluate the expression of proliferating cell nuclear antigen (pCNA) and inducible nitric oxide synthase (iNOS). Group L1 and L3 significantly decreased mononuclear cell infiltration compared with Group C in all treatment groups (p<0.05). Group L3 significantly decreased edoema compared with Group C in all groups except for treatment Group I (p<0.05). Group L2 and L3 significantly increased epithelization in treatment Group IV (p<0.05). Moreover, Group L2 and L3 significantly increased pCNA in all groups, while L2 and L3 significantly decreased iNOS expression in treatment Group II, III, and IV (p<0.05). However, no statistical difference was found between subgroups of treatment Group I in iNOS expiration (p>0.05). The results of the current examination demonstrated that LLLT can modulate mononuclear cell infiltration and edoema, and improve epithelization, as well as increase pCNA expression, whereas decrease iNOS expression during the wound healing process, therefore enhancing wound healing following ovariohysterectomy in rats
Assessment of antimicrobial activity and In Vitro wound healing potential of ZnO nanoparticles synthesized with Capparis spinosa extract
(Ekim 2023) Sezen, Selma; Ertuğrul, Muhammed Sait; Balpınar, Özge; Bayram, Cemil; Özkaraca, Mustafa; Okkay, Irmak Ferah; Hacımüftüoğlu, Ahmet; Güllüce, Medine
Agents that will accelerate wound healing maintain their clinical importance in all aspects. The aim of this study is to deter mine the antimicrobial activity of zinc oxide nanoparticles (ZnO NPs) ZnO nanoparticles obtained by green synthesis from Capparis spinosa L. extract and their efect on in vitro wound healing. ZnO NPs were synthesized and characterized using Capparis spinosa L. extract. ZnO NPs were tested against nine ATCC-coded pathogen strains to determine antimicrobial activity. The efects of diferent doses (0.0390625–20 µg/mL) of NPs on cell viability were determined by MTT assay. The efect of ZnO NPs doses (0.0390625 µg/mL, 0.078125 µg/mL, 0.15625 µg/mL, 0.3125 µg/mL, 0.625 µg/mL, 1.25 µg/mL) that increase proliferation and migration on wound healing was investigated in an in vitro wound experiment. Cell culture medium obtained from the in vitro wound assay was used for biochemical analysis, and plate alcohol-fxed cells were used for immunohistochemical staining. It was determined that NPs formed an inhibition zone against the tested Gram-positive bacteria. The ZnO NPs doses determined in the MTT test provided faster wound closure in in-vitro conditions compared to the DMSO group. Biochemical analyses showed that infammation and oxidative status decreased, while antioxidant levels increased in ZnO NPs groups. Immunohistochemical analyses showed increased expression levels of Bek/FGFR2, IGF, and TGF-β associated with wound healing. The fndings reveal the antimicrobial efect of ZnO nanoparticles obtained using Capparis spinosa L. extract in vitro and their potential applications in wound healing.
Anticancer activity of lycopene in HT?29 colon cancer cell line
(Mart 2023) Ataseven, Dilara; Öztürk, Ayşegül; Özkaraca, Mustafa; Joha, Ziad
An inverse association between serum lycopene levels and the risk of cancers has been pointed out by many prospective and retrospective epidemiological studies which prompted more studies to be performed on animal models and cell cultures in order to test this hypothesis. The aim of the present study was to evaluate the antiproliferative and pro-apoptotic efect of lycopene on colon cancer HT-29 cell line. The efect of lycopene on the viability of HT-29 cell line was investigated using XTT assay. The levels of Bcl-2, cleaved caspase 3, BAX, cleaved PARP, and 8-oxo-dG in lycopene-treated HT-29 cells were measured using ELISA. Gamma-H2AX and cytochrome c expression was assessed semi-quantitatively using immunofuores cence staining. Lycopene at doses of 10 and 20 μM produced a signifcant antiproliferative efect on HT-29 cells compared to the control (p < 0.05). The IC50 value of lycopene in HT-29 cells was found to be 7.89 μM for 24 h. Lycopene (7.89 μM) signifcantly elevated cleaved caspase 3 (p < 0.01), BAX, and cleaved PARP, 8-oxo-dG levels (p < 0.05). The levels of γ-H2AX foci are signifcantly higher while the levels of cytochrome-c are lower (p < 0.05) in lycopene-treated HT-29 cells. These results indicate that lycopene has an antiproliferative apoptotic and genotoxic efect on HT-29 colon cancer cell line
Pomegranate peel extract, N-Acetylcysteine and their combination with Ornipural alleviate Cadmium-induced toxicity in rats
(26/07/2023) Yasemin KORKMAZ; Hüseyin GÜNGÖR; Ahmet DEMİRBAŞ; Burak DİK
Cadmium is a major environmental pollutant and a highly toxic metal. It was aimed to determine the effects of pomegranate peel extract (PPE), N-acetylcysteine (NAC) alone and along with Ornipural on cadmium-induced toxicity. Forty-six Wistar Albino male rats were divided into 6 groups and the groups were formed into healthy control, Cadmium group (5 mg/kg/day, oral), Cadmium + Pomegranate peel extract (500 mg/kg, oral), Cadmium + N-acetylcysteine (100 mg/kg, oral), Cadmium + Pomegranate peel extract (500 mg/kg, oral) + Ornipural (1 mL/kg, subcutaneous) and Cadmium + N-acetylcysteine (100 mg/kg, oral) + Ornipural (1 mL/kg, subcutaneous). Cadmium accumulated heavily in both liver and kidney tissue. The administration of N-acetylcysteine and pomegranate peel extract alone reduced cadmium levels in both tissues. N-acetylcysteine treatment prevented the increase in ALT and MDA levels by cadmium damage. N-acetylcysteine + Ornipural treatment inhibited the increase in liver 8-OHdG level in the liver. N-acetylcysteine and N-acetylcysteine + Ornipural treatments prevented the reduced serum MMP2 level. N-acetylcysteine and Pomegranate peel extract + Ornipural treatments significantly reduced the increased liver iNOS level in the liver. In conclusion, NAC therapy may be a successful treatment option for cadmium toxicity. However, further research is needed on the effects of PPE and Ornipural combinations for the treatment of cadmium toxicity. In future studies, various doses of these treatment options (with chelators) should be investigated for cadmium toxicity.
Kaempferol and Isorhamnetin alleviate Lipopolysaccharide-Induced Anxiety and Depression-Like Behavioral in Balb/C Mice
(09/07/2023) Mehmet EKİCİ; Hüseyin GÜNGÖR; Derya Güliz MERT
The etiology of anxiety and depression is linked to inflammation and oxidative stress. Isorhamnetin and Kaempferol are strong antioxidants with anti-inflammatory neuroprotective properties. This study, it was aimed to investigate the effect of Kaempferol and Isorhamnetin in Lipopolysaccharide (LPS)-induced anxiety and depression model in mice. Thirty Balb/C mice were divided into six groups of five mice each weighing 25-35 g. Kaempferol (50 mg/kg and 100 mg/kg) and Isorhamnetin (30 mg/kg and 60 mg/kg) were given orally to the treatment group, and the vehicle was given to the control and LPS groups for fourteen days, followed by intraperitoneal (0.83 mg/kg) LPS injection (control group excluding) on the fifteenth day. At 3 hours after the administration of LPS, each group was applied with the Elevated Plus-Maze (EPM) test, the Light/Dark test, and the Open Field test (OFT). At 24 hours after LPS administration, the Forced Swimming Test (FST) was applied and at 28 hours, the Tail Suspension Test (TST). After the behavioral test, the prefrontal cortex and hippocampus tissues of rats were harvested by cervical dislocation under high-dose anesthesia. From these tissues, malondialdehyde (MDA) levels, total oxidant status (TOS) and total antioxidant status (TAS) levels, tumor necrosis factor alpha (TNF-α), interleukin-1beta (IL-1β), and interleukin-6 (IL-6) levels, and brain-derived neurotrophic factor (BDNF) levels were measured. Kaempferol and Isorhamnetin ameliorated LPS-induced anxiety evaluated by OFT, Light/Dark test, and EPM, and LPS-induced depression evaluated by FST and TST. Kaempferol and Isorhamnetin alleviated LPS-induced increased oxidative stress in the prefrontal cortex and hippocampus by decreasing MDA and TOS levels and increasing TAS levels. In addition, it was observed that Kaempferol and Isorhamnetin regulated the increase in prefrontal and hippocampal inflammation caused by LPS by decreasing TNF-α, IL-1β, and IL-6 levels. Most importantly, LPS reduced prefrontal and hippocampal BDNF levels, but the treatment groups reversed it. These results show the possible therapeutic potential of Kaempferol and Isorhamnetin, along with the importance of oxidative stress, inflammation, and BDNF in the etiopathogenesis of anxiety and depression.
Carvacrol Mitigates Bleomycin Induced Experimental Pulmonary Fibrosis
(23/08/2023) Nergiz Hacer TURGUT; Hüseyin GÜNGÖR; Mehmet EKİCİ; Mehmet Önder KARAYİĞİT; Haki KARA
Idiopathic pulmonary fibrosis (IPF) is a serious progressive pulmonary disease of unknown etiology and high mortality. Carvacrol is a natural phenolic monoterpene with various pharmacological effects, especially antioxidant and anti inflammatory effects. Hence, the present study aimed to investigate the effect of carvacrol on bleomycin (BLM) induced pulmonary fibrosis (PF) in Wistar albino rats. Rats were administered a single dose of BLM (5mg/kg, intratracheal) or vehicle and treated with carvacrol (100 mg/kg, p.o. for 14 days following BLM administration). For calculating the lung index, the body and lungs were weighed. The Elisa method was used to assess hydroxyproline content, anti inflammatory, and antioxidant effects. Fibrosis score, collagen deposition and inflammation were evaluated with Hematoxylin Eosin (HxE) and Masson’s trichrome staining. Inducible nitric oxide synthase (iNOS), transforming growth factor beta 1 (TGF β1), and caspase 3 expressions were assessed immunohistochemically. BLM administration significantly diminished glutathione peroxidase (GPx) and superoxide dismutase (SOD) activities and increased malondialdehyde (MDA) levels. BLM also increased tumor necrosis factor alpha (TNF α) and collagen bundle accumulation. Carvacrol at 100 mg/kg significantly decreased collagen accumulation, MDA, TNF α levels, iNOS, TGF 1, and caspase 3 expression, while increasing SOD and GPx activity. Histopathological examination supported the findings that carvacrol attenuated the degree of collagen deposition and inflammation. This study revealed that treatment with carvacrol (100 mg/kg) exhibits a potential healing effect on BLM induced PF by reducing inflammatory and oxidative damages and histopathological alterations, with possible molecular targets being iNOS, TGF β1 and caspase 3 signaling pathways.
Molecular prevalence of bovine hemoplasmosis in Turkey with first detection of Mycoplasma wenyonii and Candidatus Mycoplasma haemobos in cattle and water buffalo
(2023) EROL, Ufuk; Şahin, Ömer Faruk; ALTAY, Kürşat
Hemoplasma species can cause infection varying from mild to severe in a wide range of hosts, including cattle and water bufalo. Two hemoplasma species, Mycoplasma wenyonii and Candidatus Mycoplasma haemobos, have been reported in cattle and water bufalo from diferent parts of the world to date. There was a lack of information on the presence and distribution of these pathogens in Turkey despite the negative economic impact on livestock production. This study aimed to develop a duplex PCR assay amplifying the 16S rRNA gene, in order to analyze DNA samples obtained from 297 cattle and 360 water bufaloes, and to determine the molecular prevalence of bovine hemoplasma species in Sivas province. Bovine hemoplasma species were found in 94 of 297 (31.64%) cattle and in 17 of 360 (4.72%) water bufaloes in this study. Randomly selected six positives PCR products (three samples each species) obtained from cattle and water bufaloes were sequenced, and the consensus sequences were uploaded to GenBank. Nucleotide similarity of 96.97–100% was determined between M. wenyonii isolates obtained in this study and those of M. wenyonii isolates present in the GenBank database, whereas C. Mycoplasma haemobos isolates from this study shared 99.04–100% homology with the C. Mycoplasma haemobos isolates uploaded to the GenBank. With the current study, the molecular presence of M. wenyonii and C. Mycoplasma haemobos were documented for the frst time in cattle and water bufaloes in Turkey. Considering the rate of prevalence, veterinarians should take precautions against bovine hemoplasma species to protect animal health.
Pharmacokinetics of meloxicam following intravenous administration at different doses in sheep
(13/09/2023) Hüseyin GÜNGÖR; Orhan ÇORUM; Duygu Durna ÇORUM; Alper Serhat KUMRU; Gökhan YILMAZ; Devran COŞKUN; Alparslan COŞKUN; Kamil ÜNEY
The aim of this study is to determine the pharmacokinetic change after intravenous administration of meloxicam at doses of 0.5, 1 and 2 mg/kg to sheep. The study was carried out on six Akkaraman sheep. Meloxicam was administered intravenously to each sheep at 0.5, 1, and 2 mg/kg doses in a longitudinal pharmacokinetic design with a 15-day washout period. Plasma concentrations of meloxicam were determined using the high performance liquid chromatography-ultraviolet, and pharmacokinetic parameters were evaluated by non-compartmental analysis. Meloxicam was detected up to 48 h in the 0.5 mg/kg dose and up to 96 h in the 1 and 2 mg/kg doses. As the dose increased from 0.5 to 2 mg/kg, terminal elimination half-life, and dose normalized area under the concentration versus time curve increased and total clearance decreased. Compared to the 1 mg/kg dose, it was determined that Vdss decreased and C0.083h increased in the 2 mg/kg dose. Meloxicam provided the therapeutic concentration of >0.39 μg/mL reported in other species for 12, 48 and 96 h at 0.5, 1 and 2 mg/kg doses, respectively. These results show that meloxicam exhibits non-linear pharmacokinetics and will achieve unpredictable plasma concentrations when administered IV for a rapid effect at dose of ≥1 mg/kg in sheep.
Molecular survey of Anaplasma phagocytophilum and related variants in water buffaloes: the first detection of Anaplasma phagocytophilum-like 1
(2023) Şahin, Ömer Faruk; Erol, Ufuk; Duzlu, Onder; Altay, Kürşat
Anaplasma phagocytophilum infects various hosts and lead to mild to severe infection. Currently, two A.phagocytophilum-related variants have been documented in different countries. Although limited, there are studies revealing the presence of A.phagocytophilum in water buffaloes, but no study investigating A.phagocytophilum-like 1 and –like 2. A.phagocytophilum and related variants were investigated using PCR, PCR-RFLP, and DNA sequence analysis in water buffaloes in Türkiye. 364 buffalo blood samples were examined for A.phagocytophilum and related strains. Seven buffaloes were determined to be positive with PCR and PCR-RFLP revealed that all samples were A.phagocytophilum-like 1. According to the partial sequence of 16S rRNA gene, A.phagocytophilum like-1 may split into two different variants. This work supplies the first molecular report of A.phagocytophilum-like 1 in water buffaloes. However, a lack of information is present on the pathogen's clinical manifestations and vector species. There is still a need to investigate vectors and clinical signs of the pathogen.
Molecular detection and phylogenetic analysis of Toxocara vitulorum in feces and milk samples from naturally infected water buffaloes
(2023) Urhan, Osman Furkan; Erol, Ufuk; Altay, Kürşat
Toxocara vitulorum infects cattle and water buffalo, leading to mild to severe infection in calves and has wide geographic distributions, especially in tropical and subtropical countries. This work aimed to assess the prevalence, distributions, and phylogeny of T. vitulorum in water buffaloes in different parts of Sivas, one of the essential buffalo-breeding areas in Türkiye. T. vitulorum was found in 42 (8.23%) and 54 (10.58%) fecal (n:510) samples using microscopic and molecular techniques, respectively. T. vitulorum was higher in animals aged 0-6 months compared to other groups. Furthermore, when animals aged 0-6 months were grouped within themselves, the prevalence of T. vitulorum in 1-3 month-old-animals was higher than in both younger than one month and older than three months. T. vitulorum was detected in fecal samples obtained from animals older than six months. In colostrum/milk samples (n:100), T. vitulorum-larvae were found in 4% and 10% with microscopic and molecular techniques, respectively. The larvae were detected in colostrum/milk samples in the mother between the 2nd and 28th days postpartum-period. The ITS-1-gene of 11 PCR-positive samples was sequenced. The 98.99–100% nucleotide identity was determined between our T. vitulorum isolates and those present in GenBank. In conclusion, this is the first molecular survey and phylogenetic analysis of T. vitulorum in fecal and colostrum/milk samples from naturally infected water buffaloes. Data obtained in this study will help to understand the life cycle and epidemiology of the nematode. Data also revealed that veterinarians should consider older animals as well as young animals in their control program of nematode infections in farms.

Güncel Gönderiler