<?xml version="1.0" encoding="UTF-8"?>
<!DOCTYPE article PUBLIC "-//NLM//DTD JATS (Z39.96) Journal Publishing DTD v1.4 20241031//EN"
        "https://jats.nlm.nih.gov/publishing/1.4/JATS-journalpublishing1-4.dtd">
<article  article-type="research-article"        dtd-version="1.4">
            <front>

                <journal-meta>
                                                                <journal-id>ahi evran med j</journal-id>
            <journal-title-group>
                                                                                    <journal-title>Ahi Evran Medical Journal</journal-title>
            </journal-title-group>
                                        <issn pub-type="epub">2619-9203</issn>
                                                                                            <publisher>
                    <publisher-name>Kirsehir Ahi Evran University</publisher-name>
                </publisher>
                    </journal-meta>
                <article-meta>
                                        <article-id pub-id-type="doi">10.46332/aemj.1759173</article-id>
                                                                <article-categories>
                                            <subj-group  xml:lang="en">
                                                            <subject>Emergency Medicine</subject>
                                                            <subject>Clinical Sciences (Other)</subject>
                                                    </subj-group>
                                            <subj-group  xml:lang="tr">
                                                            <subject>Acil Tıp</subject>
                                                            <subject>Klinik Tıp Bilimleri (Diğer)</subject>
                                                    </subj-group>
                                    </article-categories>
                                                                                                                                                        <title-group>
                                                                                                                        <article-title>High Dose Flaxseed Exposure Induces Dose-Dependent Histopathological Alterations in Rat Lung Tissue: An Experimental Model of Cyanogenic Toxicity</article-title>
                                                                                                                                                                                                <trans-title-group xml:lang="tr">
                                    <trans-title>Keten Tohumunun Yüksek Dozda Uygulanmasının Rat Akciğer Dokusunda Doz Bağımlı Histopatolojik Değişikliklere Yol Açması: Deneysel Bir Siyanür Toksisitesi</trans-title>
                                </trans-title-group>
                                                                                                    </title-group>
            
                                                    <contrib-group content-type="authors">
                                                                        <contrib contrib-type="author">
                                                                    <contrib-id contrib-id-type="orcid">
                                        https://orcid.org/0000-0002-5749-3753</contrib-id>
                                                                <name>
                                    <surname>Armağan</surname>
                                    <given-names>Hamit Hakan</given-names>
                                </name>
                                                                    <aff>SULEYMAN DEMIREL UNIVERSITY, SCHOOL OF MEDICINE</aff>
                                                            </contrib>
                                                    <contrib contrib-type="author">
                                                                    <contrib-id contrib-id-type="orcid">
                                        https://orcid.org/0000-0002-7595-2175</contrib-id>
                                                                <name>
                                    <surname>Hatip</surname>
                                    <given-names>Ahmet Yunus</given-names>
                                </name>
                                                                    <aff>SÜLEYMAN DEMİREL ÜNİVERSİTESİ, TIP FAKÜLTESİ</aff>
                                                            </contrib>
                                                    <contrib contrib-type="author">
                                                                    <contrib-id contrib-id-type="orcid">
                                        https://orcid.org/0000-0002-9214-3994</contrib-id>
                                                                <name>
                                    <surname>Oğuzlar</surname>
                                    <given-names>Furkan Çağrı</given-names>
                                </name>
                                                                    <aff>SULEYMAN DEMIREL UNIVERSITY, SCHOOL OF MEDICINE</aff>
                                                            </contrib>
                                                    <contrib contrib-type="author">
                                                                    <contrib-id contrib-id-type="orcid">
                                        https://orcid.org/0000-0002-8080-9429</contrib-id>
                                                                <name>
                                    <surname>Armağan</surname>
                                    <given-names>İlkay</given-names>
                                </name>
                                                                    <aff>SULEYMAN DEMIREL UNIVERSITY, SCHOOL OF MEDICINE</aff>
                                                            </contrib>
                                                                                </contrib-group>
                        
                                        <pub-date pub-type="pub" iso-8601-date="20260429">
                    <day>04</day>
                    <month>29</month>
                    <year>2026</year>
                </pub-date>
                                        <volume>10</volume>
                                        <issue>1</issue>
                                        <fpage>59</fpage>
                                        <lpage>65</lpage>
                        
                        <history>
                                    <date date-type="received" iso-8601-date="20250805">
                        <day>08</day>
                        <month>05</month>
                        <year>2025</year>
                    </date>
                                                    <date date-type="accepted" iso-8601-date="20251206">
                        <day>12</day>
                        <month>06</month>
                        <year>2025</year>
                    </date>
                            </history>
                                        <permissions>
                    <copyright-statement>Copyright © 2017, Ahi Evran Medical Journal</copyright-statement>
                    <copyright-year>2017</copyright-year>
                    <copyright-holder>Ahi Evran Medical Journal</copyright-holder>
                </permissions>
            
                                                                                                <abstract><p>Purpose: Flaxseed (Linum usitatissimum L.) is a widely consumed functional food rich in omega-3 fatty acids, lignans, and fiber. However, due to its cyanogenic glycoside content, excessive consumption may lead to toxic effects. This study aimed to evaluate the histopathological effects of high-dose oral flaxseed administration on rat lung tissue.Materials and Methods: Thirty-two adult female Wistar Albino rats were randomly divided into four groups (n=8 each): Control, Low Dose (1.4 g/kg/day), Medium Dose (2.8 g/kg/day), and High Dose (5.6 g/kg/day). Flaxseed was administered via oral gavage for seven days. At the end of the experiment, the rats were sacrificed under anesthesia. Lung tissues were fixed in 10% neutral for-malin, stained with H&amp;E, and examined under light microscopyResults: No pathological changes were observed in the control and low-dose groups. In the medium-dose group, vascular congestion was noted. The high-dose group exhibited vascular congestion, mononuclear cell infiltration, and interalveolar septal thickening. These findings indicate that flaxseed administration induces dose-dependent inflammatory and structural alterations in lung tissueConclusion: Short-term high-dose flaxseed intake causes significant histopathological changes in rat lung tissue. Findings such as vascular congestion, inflammatory infiltration, and septal thickening suggest potential pulmonary toxicity. The absence of similar findings at lower doses supports a dose-dependent relationship. These results emphasize the need for cautious use of functional herbal products and encourage further biochemical and molecular studies to elucidate underlying mechanisms.</p></abstract>
                                                                                                                                    <trans-abstract xml:lang="tr">
                            <p>Amaç: Keten tohumu (Linum usitatissimum L.), omega-3 yağ asitleri, lignanlar ve lif bakımından zengin olması nedeniyle yaygın tüketilen fonksiyonel bir gıdadır. Ancak içerdiği siyanojenik glikozitler nedeniyle aşırı tüketimi toksik etkilere yol açabilir. Bu çalışmada, yüksek doz oral keten tohumu uygulamasının rat akciğer dokusunda oluşturduğu histopatolojik etkiler değerlendirildi.Araçlar ve Yöntem: 32 erişkin dişi Wistar Albino rat, sekizerli dört gruba ayrıldı: Kontrol, Düşük Doz (1.4 g/kg/gün), Orta Doz (2.8 g/kg/gün) ve Yüksek Doz (5.6 g/kg/gün). Keten tohumu oral gavaj yoluyla 7 gün boyunca uygulandı. Deney sonunda akciğer dokuları çıkarılarak %10 nötral formalinle tespit edildi, H-E ile boyandı ve ışık mikroskobunda değerlendirildi.Bulgular: Kontrol ve düşük doz gruplarında patolojik bulgu saptanmadı. Orta doz grubunda vasküler konjesyon izlenirken, yüksek doz grubunda vasküler konjesyonla birlikte mononükleer hücre infiltrasyonu ve interalveolar septum kalınlaşması görüldü. Bulgular, keten tohumunun doza bağlı olarak akciğer dokusunda inflamasyon ve yapısal değişikliklere yol açabileceğini göstermektedir.Sonuç: Yüksek dozda kısa süreli keten tohumu alımı, rat akciğer dokusunda belirgin histopatolojik değişikliklere neden olmuştur. Bulgular, keten tohumunun yüksek dozlarda potansiyel pulmoner toksisite riski taşıdığını göstermektedir. Bitkisel içerikli fonksiyo-nel gıdaların aşırı tüketimi konusunda dikkatli olunmalı; ileri biyokimyasal ve moleküler çalışmalarla mekanizmalar aydınlatıl-malıdır.</p></trans-abstract>
                                                            
            
                                                            <kwd-group>
                                                    <kwd>cyanogenic glycosides</kwd>
                                                    <kwd>  Flaxseed</kwd>
                                                    <kwd>  pulmonary toxicity</kwd>
                                            </kwd-group>
                                                        
                                                                            <kwd-group xml:lang="tr">
                                                    <kwd>Keten tohumu</kwd>
                                                    <kwd>  pulmoner toksisite</kwd>
                                                    <kwd>  siyanojenik glikozit</kwd>
                                            </kwd-group>
                                                                                                        <funding-group specific-use="FundRef">
                    <award-group>
                                                                            <award-id>15/09/2022 06/87</award-id>
                                            </award-group>
                </funding-group>
                                </article-meta>
    </front>
    <back>
                            <ref-list>
                                    <ref id="ref1">
                        <label>1</label>
                        <mixed-citation publication-type="journal">1. Oomah, B. D., Mazza, G., &amp; Kenaschuk, E. O. (1992). Cyanogenic compounds in flaxseed. Journal of Agricultural and Food chemistry, 40(8), 1346-1348. doi:10.1021/jf00020a010</mixed-citation>
                    </ref>
                                    <ref id="ref2">
                        <label>2</label>
                        <mixed-citation publication-type="journal">2. Rabetafika HN, Van Remoortel V, Danthine S, Paquot M, Blecker C. Flaxseed proteins: food uses and health benefits. Int J Food Sci Technol. 2011;46(2):221-228. doi:10.1111/j.1365-2621.2010.02477.x.</mixed-citation>
                    </ref>
                                    <ref id="ref3">
                        <label>3</label>
                        <mixed-citation publication-type="journal">3. Mueed, A., Shibli, S., Jahangir, M., Jabbar, S., &amp; Deng, Z. (2023). A comprehensive review of flaxseed (Linum
usitatissimum L.): health-affecting compounds, mechanism of toxicity, detoxification, anticancer and potential risk. . Critical Reviews in Food Science and Nutrition, 63(32), 11081-11104. doi:10.1080/10408398.2022.2092718</mixed-citation>
                    </ref>
                                    <ref id="ref4">
                        <label>4</label>
                        <mixed-citation publication-type="journal">4. İşleroğlu, H., &amp; Yıldırım, Z. Y. M. (2005). Fonksiyonel bir gıda olarak keten tohumu. Journal of Agricultural Faculty of Gaziosmanpaşa University (JAFAG), 2005(2), 23-30.Link: https://izlik.org/JA33YW83PY</mixed-citation>
                    </ref>
                                    <ref id="ref5">
                        <label>5</label>
                        <mixed-citation publication-type="journal">5. Nelson L. Acute cyanide toxicity: mechanisms and manifestations. J Emerg Nurs. 2006;32(4):S8-S11.
doi:10.1016/j.jen.2006.05.012.</mixed-citation>
                    </ref>
                                    <ref id="ref6">
                        <label>6</label>
                        <mixed-citation publication-type="journal">6. Baker, A., Garner, M. C., Kimberley, K. W., Sims, D. B., Stordock, J. H., Taggart, R. P., &amp; Walton, D. J. (2018). Cyanide toxicity of freshly prepared smoothies and juices frequently consumed. European journal of nutrition &amp; food safety, 8(4), 215. doi: 10.9734/ejnfs/2018/44004</mixed-citation>
                    </ref>
                                    <ref id="ref7">
                        <label>7</label>
                        <mixed-citation publication-type="journal">7. Banea-Mayambu JP, Tylleskär T, Tylleskär K, Gebre-Medhin M, Rosling H. Dietary cyanide from insufficiently processed cassava and growth retardation in children in the Democratic Republic of Congo (formerly Zaire). Ann Trop Paediatr. 2000;20(1):34-40. doi:10.1080/02724930092048</mixed-citation>
                    </ref>
                                    <ref id="ref8">
                        <label>8</label>
                        <mixed-citation publication-type="journal">8. Armağan İ, Yeşilot Ş. Excessive use of flaxseed may pose a threat to kidney tissue: an experimental study. Med J SDU. 2023;30(1):89-96. doi: 10.17343/sdutfd.1247065.</mixed-citation>
                    </ref>
                                    <ref id="ref9">
                        <label>9</label>
                        <mixed-citation publication-type="journal">9. Özgçmen, M. (2020). Bilinçsiz Tüketilen Keten Tohumunun Kemik Doku Üzerine Etkisi. Süleyman Demirel Üniversitesi Sağlık Bilimleri Dergisi, 11(2), 206-211. Link: https://izlik.org/JA52ER35DW</mixed-citation>
                    </ref>
                                    <ref id="ref10">
                        <label>10</label>
                        <mixed-citation publication-type="journal">10. Rittirsch, D., Huber-Lang, M. S., Flierl, M. A., &amp; Ward, P. A. (2009). Immunodesign of experimental sepsis by cecal ligation and puncture. Nature protocols, 4(1), 31-36. doi: 10.1038/nprot.2008.214</mixed-citation>
                    </ref>
                                    <ref id="ref11">
                        <label>11</label>
                        <mixed-citation publication-type="journal">11. Food and Drug Administration. (2005). Estimating the safe starting dose in clinical trials for therapeutics in adult healthy volunteers. Rockville, Maryland, USA: US: Food and Drug administration. Link:https://www.fda.gov/media/72309/download</mixed-citation>
                    </ref>
                                    <ref id="ref12">
                        <label>12</label>
                        <mixed-citation publication-type="journal">12. Raška F, Lipový B, Hladík M, Holoubek J. Cyanide poisoning in patients with inhalation injury—the phantom menace. Acta Chir Plast. 2021;63(4):185-189. doi:10.48095/ccachp2021185</mixed-citation>
                    </ref>
                                    <ref id="ref13">
                        <label>13</label>
                        <mixed-citation publication-type="journal">13. Vetter J. Plant cyanogenic glycosides. Toxicon. 2000;38(1):11-36. doi:10.1016/S0041-0101(99)00128-2</mixed-citation>
                    </ref>
                                    <ref id="ref14">
                        <label>14</label>
                        <mixed-citation publication-type="journal">14. Tahermohammadi, H., Kaveh, S., &amp; Sadr, S. (2021). Possible effect and mechanism of action of flaxseed on cystic fibrosis pulmonary disorder: a medical hypothesis. Journal of Pediatric Perspectives, 9(9), 14400-14412. doi:10.22038/ijp.2020.53208.4218</mixed-citation>
                    </ref>
                            </ref-list>
                    </back>
    </article>
