Publications by authors named "Kerimali Akyıldız"

7 Publications

  • Page 1 of 1

Apelin-13 activates the hippocampal BDNF/TrkB signaling pathway and suppresses neuroinflammation in male rats with cisplatin-induced cognitive dysfunction.

Behav Brain Res 2021 Jun 15;408:113290. Epub 2021 Apr 15.

Recep Tayyip Erdogan University, Faculty of Medicine, Department of Biochemistry, Rize, Turkey. Electronic address:

It has been established that cisplatin causes neuronal damage and cognitive impairment. However, the mechanism is not sufficiently clear. Apelin-13 is an endogenous peptide with strong neuroprotective effects through the synthesis of neurotrophic factors and suppression of inflammation. The aim of this study was to investigate the role of brain-derived neurotrophic factor/tropomyosin receptor kinase B (BDNF/TrkB) signaling pathway and the potential inhibitory effects of apelin-13 in the mechanism of cisplatin-induced hippocampal damage and cognitive impairment. Apelin-13 was administered to adult sprague dawley male rats at a dose of 20 nmol/kg every day for 4 weeks, cisplatin was administered at a dose of 5 mg/kg once a week for 4 weeks. The spatial and recognition memory tests of the rats were performed on the 5th week. BDNF and the inflammatory cytokines tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) levels were measured by ELISA in hippocampal homogenates. Pyramidal neuron and glial cell damage in the hippocampal CA1, CA3 and dentate gyrus (DG) were analyzed histologically. TrkB activity in the hippocampus was determined by immunohistochemical methods. Cisplatin impaired spatial and recognition memory in rats, while apelin-13 improved spatial memory but did not affect recognition memory. Cisplatin suppressed BDNF in the hippocampus while increased IL-1β and TNF-α. In contrast, apelin-13 administration increased BDNF but significantly suppressed TNF-α and IL-1B. Cisplatin caused pyramidal neuron and glial cell damage in CA1, CA3 and DG. In the cisplatin + apelin-13 group, however, pyramidal neuron and glial cell damage was less than those without apelin-13. Cisplatin increased TrkB activity in the hippocampus, which was counteracted by apelin-13. In conclusion, apelin-13 reduced the cisplatin-induced cognitive deficiency, by suppressing inflammation and stimulating the synthesis and activation of neurotrophic factors in hippocampal tissue.
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http://dx.doi.org/10.1016/j.bbr.2021.113290DOI Listing
June 2021

Melatonin improves periodontitis-induced kidney damages by decreasing inflammatory stress and apoptosis in rats.

J Periodontol 2020 Nov 30. Epub 2020 Nov 30.

3D Medical and Industrial Design Laboratory, Istanbul University, Istanbul, Turkey.

Background: Two main aims of this animal study were to inspect the possible effects of periodontitis on the structure and functions of the kidneys and the therapeutic effectiveness of melatonin.

Methods: Twenty-four male Sprague-Dawley rats were randomly divided into three groups: control, experimental periodontitis (Ep), and Ep-melatonin (Ep-Mel). Periodontitis was induced by placing 3.0-silk sutures sub-paramarginally around the cervix of right-left mandibular first molars and maintaining the sutures for 5 weeks. Then melatonin (10 mg/kg body weight/day, 14 days), and the vehicle was administered intraperitonally. Mandibular and kidney tissue samples were obtained following the euthanasia. Periodontal bone loss was measured via histological and microcomputed tomographic slices. On right kidney histopathological and immunohistochemical, and on the left kidney biochemical (malonyl-aldehyde [MDA], glutathione, oxidative stress [OSI], tumor necrosis factor [TNF]-α, interleukin [IL]-1β, matrix metalloproteinase [MMP]-8, MMP-9, and cathepsin D levels) evaluations were performed. Renal functional status was analyzed by levels of serum creatinine, urea, cystatin-C, and urea creatinine.

Results: Melatonin significantly restricted ligature-induced periodontal bone loss (P <0 .01) and suppressed the levels of proinflammatory cytokines (TNF-α and IL-1β), oxidative stress (MDA and OSI), and proteases (MMP-8, MMP-9, and CtD) that was significantly higher in the kidneys of the rats with periodontitis (P <0.05). In addition, periodontitis-related histological damages and apoptotic activity were also significantly lower in the Ep-Mel group (P <0.05). However, the markers of renal function of the Ep group were detected slightly impaired in comparison with the control group (P >0.05); and the therapeutic activity of melatonin was limited (P >0.05).

Conclusion: Melatonin restricts the periodontitis-induced inflammatory stress, apoptosis, and structural but not functional impairments.
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http://dx.doi.org/10.1002/JPER.20-0434DOI Listing
November 2020

Melatonin ameliorates periodontitis-related inflammatory stress at cardiac left ventricular tissues in rats.

J Periodontol 2020 11 19;91(11):1486-1494. Epub 2020 May 19.

School of Medicine, Department of Biochemistry, Recep Tayyip Erdogan University, Rize, Turkey.

Background: The aim of this experimental rat study was to investigate the potential inflammatory effects of periodontitis on cardiac left ventricular tissue and the therapeutic activity of melatonin on these effects.

Methods: Twenty-four male Sprague-Dawley rats were randomly divided into three groups: control, experimental periodontitis (Ep), and Ep-melatonin (Ep-Mel). Experimental periodontitis was induced by placing and maintaining 3.0 silk ligatures at a peri marginal position on the left and right mandibular first molars for 5 weeks. Afterward, following the removal of ligatures, melatonin (10 mg/body weight) to Ep-Mel group, and vehicle (saline) to Ep and control groups were administered intraperitoneally for 14 days. On the first day of the eighth week, mandibular and cardiac left ventricular tissue samples were obtained following the euthanasia of the rats in all groups. Alveolar bone loss measurements were made on histological and microcomputed tomographic slices. Cardiac tissue levels of malondialdehyde (MDA), glutathione (GSH), superoxide dismutase (SOD), catalase (CAT), matrix metalloproteinase-9 (MMP-9), and cardiac Troponin-T (cTnT) were evaluated by appropriate biochemical methods.

Results: Measurements made on the histological and microcomputed tomographic slices showed that melatonin significantly limits the ligature-induced periodontal tissue destruction (P <0.01). In addition, melatonin was detected to cause a significant decrease of MDA, MMP-9, and cTnT levels which were found to be significantly higher on rats with Ep (P <0.05) while having no significant effect on antioxidant levels (GSH, SOD, and CAT) (P >0.05).

Conclusion: Melatonin might be regarded as an important supportive therapeutic agent to reduce the early degenerative changes and possible hypertrophic remodeling at cardiac left ventricular tissues provoked by periodontitis-related bacteria and/or periodontal inflammation.
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http://dx.doi.org/10.1002/JPER.19-0685DOI Listing
November 2020

Prenatal Effects of a 1,800-MHz Electromagnetic Field on Rat Livers.

Cells Tissues Organs 2019 4;207(3-4):187-196. Epub 2019 Dec 4.

Department of Medical Services and Techniques, Health Care Services Vocational School, Recep Tayyip Erdogan University, Rize, Turkey.

The use of devices, including mobile phones, generating electromagnetic fields (EMF) is widespread and is progressively increasing. It has also been shown that EMF may have detrimental effects. This is the first study to investigate the postnatal biochemical and histological effects of prenatal exposure of rat livers to 1,800-MHz EMF at different time intervals in uteroplacental life. The 3 EMF groups of rats were exposed to 1,800-MHz EMF for 6, 12, or 24 h daily for 20 days. Unexposed rats served as control group. All rats were subjected to anesthesia, and on postnatal day 60, the livers were excised, and blood was collected for histological and biochemical analyses. Malondialdehyde levels were significantly higher in the exposed groups than the unexposed controls (p < 0.05). In contrast, EMF-exposed groups had lower liver tissue glutathione levels than controls (p < 0.05). Serum Ca2+, alanine transaminase, and aspartate aminotransferase levels were higher in EMF-exposed groups than controls (p < 0.05). In addition, liver tissue total oxidant status levels were increased (p < 0.05), and liver tissue total antioxidant status levels were decreased (p < 0.05) compared to the control group. Furthermore, in the EMF groups, extensive vacuolation and degeneration of the hepatocytes in the portal area, as well as those surrounding the sinusoids, were evident. Affected hepatocytes had polygonally shaped nuclei and vacuolic cytoplasm imparting eosinophilic staining. Loss of cellular membrane integrity and invaginations, as well as picnotic nuclei, was prominent. This study has shown that intrauterine liver damage caused by 1,800-MHz EMF exposure persists into puberty in rats.
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http://dx.doi.org/10.1159/000504506DOI Listing
July 2020

Effects of Gadodiamide and Gadoteric Acid on Rat Kidneys: A Comparative Study.

J Magn Reson Imaging 2019 02 13;49(2):382-389. Epub 2018 Sep 13.

Recep Tayyip Erdogan University Faculty of Medicine, Department of Biochemistry, Rize, Turkey.

Background: Gadolinium-based contrast agents are complex chelates to provide contrast in NRI. However, recent studies have highlighted the deposition of free Gd ion in various tissues.

Purpose: To evaluate the histopathological and immunohistochemical changes on rat kidney tissue following both macrocyclic (gadoteric acid) and linear (gadodiamide) agents under the hypothesis that gadolinium-based contrast agents (GBCA) lead to toxic, free Gd accumulation in tissues.

Study Type: The local Animal Care Committee approved the prospective animal study.

Animal Model: Thirty-two healthy Sprague-Dawley male rats were administered 2 mmol/kg gadodiamide and gadoteric acid for the first 4 days for 5 weeks. Group 1 received no drug (control, n = 8) and Group 2 (n = 8) was administered 0.1 ml/kg saline. Group 3 was administered 0.1 mmol/kg gadodiamide and Group 4 (n = 8) was administered 2 mmol/kg gadoteric acid.

Assessment: Biochemical, histopathological, and immunohistochemical changes in testis kidney tissue were evaluated at the end of 10 weeks.

Statistical Tests: Differences between groups were analyzed using the nonparametric Kruskal-Wallis test followed by one-way analysis of variance and the Tamhane test, also followed by Turkey's HSD test.

Results: Gadolinium increased serum urea, Ca , and Caspase-3 positive tubular cell number. Larger Bowman capsules shrank proximal and distal tubules were revealed in the gadodiamide and gadoteric acid groups compared to the control group (P < 0.05). Histopathologic examination showed significantly more interstitial fibrosis, amyloid deposits, and vasocongestion in the gadodiamide group than the gadoteric acid and control groups, while the gadoteric acid group demonstrated significantly more leukocytic infiltration with atrophied proximal and distal tubules than the gadodiamide and control groups (P < 0.05).

Data Conclusion: GBCA administration causes significant histopathologic changes in kidney tissue. This study advocates additional investigation to assess the in vivo safety of GBCAs.

Level Of Evidence: 1 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2019;49:382-389.
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http://dx.doi.org/10.1002/jmri.26266DOI Listing
February 2019

The protective effects of astaxanthin against cisplatin-induced retinal toxicity.

Cutan Ocul Toxicol 2019 Mar 9;38(1):59-65. Epub 2019 Jan 9.

b Department of Histology and Embryology, Faculty of Medicine , Recep Tayyip Erdogan University , Rize , Turkey.

Purpose: This study investigated the toxic effects of an antineoplastic agent, cisplatin (CIS), on retinal cells and the potential capacity of astaxanthin (ASTA) to elicit a future therapeutic protocol in CIS-induced retinal toxicity.

Materials And Methods: Six groups were formed for the assessment; control (healthy; Group 1), olive oil (olive oil only; Group 2), ASTA control group (ASTA only, Group 3), the single intraperitoneal (IP) dose of 16 mg/kg CIS (CIS only group; Group 4), 16 mg/kg CIS +25 mg/kg (IP) ASTA (Group 5), and 16 mg/kg CIS +75 mg/kg (IP) ASTA (Group 6). On the third day after CIS administration, rats in all groups were sacrificed under anesthesia and the analysis of the biochemical parameters and histopathological levels were performed.

Results: A significant decrease in GSH levels and increases in MDA, eNOS, and 8-OHdG expressions were recorded. Additionally, CIS treatment had caused acidophilic staining in retinal histological appearance. ASTA treatment reduced the increases in MDA, eNOS, and 8-OHdG levels following CIS administration and increased the levels of GSH expressions, as well.

Conclusions: These results may suggest that the ASTA molecule as a promising option to prevent retinal toxicity in patients receiving CIS treatment for malignant tumors.
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http://dx.doi.org/10.1080/15569527.2018.1518330DOI Listing
March 2019

Effects of gadolinium-based MRI contrast agents on liver tissue.

J Magn Reson Imaging 2018 11 1;48(5):1367-1374. Epub 2018 Apr 1.

Department of Biochemistry, Recep Tayyip Erdogan University, Rize, Turkey.

Background: MRI with contrast is often used clinically. However, recent studies have reported a high accumulation of gadolinium-based contrast agents (GBCAs) in kidney, liver, and spleen tissues in several mouse models.

Purpose: To compare the effects on liver tissue of gadolinium-based MRI contrast agents in the light of biochemical and histopathological evaluation.

Study Type: Institutional Review Board (IRB)-approved controlled longitudinal study.

Animal Model: In all, 32 male Sprague-Dawley rats were divided into a healthy control group subjected to no procedure (Group 1), a sham group (Group 2), a gadodiamide group (Group 3), and a gadoteric acid group (Group 4).

Field Strength/sequence: Not applicable.

Assessment: Liver tissues removed at the end of the fifth week and evaluated pathologically (scored Knodell's histological activity index [HAI] method by two histopathologists) immunohistochemical (caspase-3 and biochemical tests (AST, ALT, TAS, TOS, and OSI method by Erel et al) were obtained.

Statistical Tests: Differences between groups were analyzed using the nonparametric Kruskal-Wallis test followed by the Tamhane test, and one-way analysis of variance (ANOVA) followed by Turkey's HSD test.

Results: An increase was observed in histological activity scores in sections from rats administered gadodiamide and gadoteric acid, and in caspase-3, AST and ALT values (P < 0.05). In contrast, we determined no change in TOS (P = 0.568 and P = 0.094, respectively), TAS (P = 0.151 and P = 0.055, respectively), or OSI (P = 0.949 and P = 0.494, respectively) values.

Data Conclusion: These data suggest that gadodiamide and gadoteric acid trigger hepatocellular necrosis and apoptosis by causing damage in hepatocytes, although no change occurs in total antioxidant and antioxidant capacity.

Level Of Evidence: 1 Technical Efficacy: Stage 4 J. Magn. Reson. Imaging 2018;47:1367-1374.
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http://dx.doi.org/10.1002/jmri.26031DOI Listing
November 2018