Carvacrol, sodyum arsenit kaynaklı ince bağırsak toksisitesini iyileştirmektedir

Yıl 2023, Cilt: 12 Sayı: 2, 132 - 137, 22.06.2023

Mustafa İleritürk , Özge Kandemir

https://doi.org/10.46810/tdfd.1294861

Öz

Arsenik, doğal ve antropojenik faaliyetler yoluyla çevrede bol miktarda bulunan son derece tehlikeli bir metaldir. Bununla beraber doğal flavonoidlerle tedavinin arsenik toksisitesine karşı koruyucu etkisi olabileceği öngörülmektedir. Carvacrol (CRV) antioksidan, anti-inflamatuvar ve antiapoptotik özellikleri bilinen doğal bir fenolik bileşiktir. Bu çalışmanın amacı sodyum arsenit (SA) ile oluşturulan ince bağırsak toksisitesinde CRV’nin koruyucu etkilerinin araştırılmasıdır. Bu amaçla ratlar rastgele 5 gruba ayrıldı ve 14 gün boyunca oral olarak SA ve CRV uygulaması gerçekleştirildi. Veriler SA uygulaması ile lipid peroksidasyonunun şekillendiğini antioksidan enzim aktivitelerinin ise azaldığını göstermektedir. Antioksidan savunma durumundaki bu bozukluk CRV uygulaması ile azaldı. NF-κB ve IL-1β ekspresyon düzelerine bakıldığına SA uygulaması ile inflamasyonun şiddetlendiği CRV uygulaması ile bu şiddetin azaldığı tespit edildi. Buna ek olarak yine SA uygulanan ratlarda artan Caspase-3 ve Apaf1 ekspresyon düzeylerinin CRV uygulaması ile düştüğü ve apoptozun şiddetinin azaldığı belirlendi. Tüm bu veriler ışığında SA kaynaklı ince bağırsak toksisitesinde CRV’nin antioksidan, anti-inflamatuvar ve antiapoptotik etki göstererek dokuları hasarda koruduğu söylenebilir.

Anahtar Kelimeler

Apoptoz, Carvacrol, Oksidatif stres, Sodyum arsenit, İnce bağırsak toksisitesi, İnflammasyon

Carvacrol ameliorates sodium arsenite-induced intestinal toxicity

Öz

Arsenic is a very dangerous metal that is widely distributed in the environment as a result of anthropogenic and natural processes. On the other hand, it is thought that treatment with natural flavonoids may protect against arsenic toxicity. Carvacrol (CRV) is a naturally occurring phenolic compound with anti-inflammatory, anti-apoptotic, and antioxidant properties. This study aims to investigate the protective effects of CRV on sodium arsenite (SA)-induced intestinal toxicity. For this purpose, rats were randomly divided into five groups and administered SA and CRV orally for 14 days. The data indicate that when SA is administered, lipid peroxidation increase and antioxidant enzyme activities decrease. The administration of CRV ameliorated this impairment in the antioxidant defense system. Examining the expression levels of NF-kB and IL-1 revealed that inflammation increased with SA application but decreased with CRV administration. Moreover, the expression levels of Caspase-3 and Apaf1 increased in rats treated with SA, whereas the severity of apoptosis decreased when CRV was administered. In light of these findings, it is possible to state that CRV protects tissues from damage by presenting antioxidant, anti-inflammatory, and anti-apoptotic effects in SA-induced intestinal toxicity.

Anahtar Kelimeler

Apoptosis, Carvacrol, Inflammation, Oxidative stress, Sodium arsenite, Intestinal toxicity

Kaynakça

• Nikravesh M, Mahdavinia M, Neisi N, Khorsandi L, Khodayar MJ. Citicoline ameliorates arsenic-induced hepatotoxicity and diabetes in mice by overexpression of VAMP2, PPAR-gamma, As3MT, and SIRT3. Pestic Biochem Physiol. 2023;192:105391.
• Anetor JJ, Wanibuchi H, Fukushima S. Arsenic exposure and its health effects and risk of cancer in developing countries: Micronutrients as host defence. Asian Pac J Cancer P. 2007;8(1):13-23.
• Liu RQ, Kong SQ, Shao YX, Cai DW, Bai B, Wei XG, et al. Chorover, Mechanisms and health implications of toxicity increment from arsenate-containing iron minerals through in vitro gastrointestinal digestion. Geoderma. 2023;432:116377.
• Brown KG, Ross GL. Arsenic, drinking water, and health: A position paper of the American Council on Science and Health. Regul Toxicol Pharm. 2002;36(2):162-174.
• Caglayan C, Demir Y, Kucukler S, Taslimi P, Kandemir FM, Gulcin I. The effects of hesperidin on sodium arsenite-induced different organ toxicity in rats on metabolic enzymes as antidiabetic and anticholinergics potentials: A biochemical approach. J Food Biochem. 2019;43(2): e12720.
• Akaras N, Gur C, Kucukler S, Kandemir FM. Zingerone reduces sodium arsenite-induced nephrotoxicity by regulating oxidative stress, inflammation, apoptosis and histopathological changes. Chem Biol Interact. 2023;374:110410.
• Kuzu M, Kandemir FM, Yildirim S, Caglayan C, Kucukler S. Attenuation of sodium arsenite-induced cardiotoxicity and neurotoxicity with the antioxidant, anti-inflammatory, and antiapoptotic effects of hesperidin. Environ Sci Pollut Res Int. 2021;28(9):10818-10831.
• Turk E, Kandemir FM, Yildirim S, Caglayan C, Kucukler S, Kuzu M. Protective Effect of Hesperidin on Sodium Arsenite-Induced Nephrotoxicity and Hepatotoxicity in Rats. Biol Trace Elem Res. 2019;189(1):95-108.
• Yesildag K, Gur C, Ileriturk M, Kandemir FM. Evaluation of oxidative stress, inflammation, apoptosis, oxidative DNA damage and metalloproteinases in the lungs of rats treated with cadmium and carvacrol. Molecular Biology Reports. 2022;49(2):1201-1211.
• Nouri A, Izak-Shirian F, Fanaei V, Dastan M, Abolfathi M, Moradi A, Khaledi M, Mirshekari-Jahangiri H. Carvacrol exerts nephroprotective effect in rat model of diclofenac-induced renal injury through regulation of oxidative stress and suppression of inflammatory response. Heliyon. 2021;7(11): e08358.
• Kandemir FM, Caglayan C, Darendelioglu E, Kucukler S, Izol E, Kandemir O. Modulatory effects of carvacrol against cadmium-induced hepatotoxicity and nephrotoxicity by molecular targeting regulation. Life Sciences. 2021;277:119610.
• Gur C, Akarsu SA, Akaras N, Tuncer SC, Kandemir FM. Carvacrol reduces abnormal and dead sperm counts by attenuating sodium arsenite-induced oxidative stress, inflammation, apoptosis, and autophagy in the testicular tissues of rats. Environ Toxicol. 2023;38: 1265-1276.
• Riaz M, Al Kury LT, Atzaz N, Alattar A, Alshaman R, Shah FA, et al. Carvacrol Alleviates Hyperuricemia-Induced Oxidative Stress and Inflammation by Modulating the NLRP3/NF-kappa B. Drug Des Dev Ther. 2022;16:1159-1170.
• Placer ZA, Cushman LL, Johnson BC. Estimation of product of lipid peroxidation (malonyl dialdehyde) in biochemical systems. Anal Biochem. 1966;16(2):359-364.
• Sun Y, Oberley LW, Li Y. A simple method for clinical assay of superoxide dismutase. Clin Chem. 1988;34(3):497-500.
• Aebi H. Catalase in vitro. Methods Enzymol. 1984;105:121-126.
• Lawrence RA, Burk RF. Glutathione peroxidase activity in selenium-deficient rat liver. Biochem Biophys Res Commun. 1976;71(4):952-958.
• Sedlak J, Lindsay RH. Estimation of total, protein-bound, and nonprotein sulfhydryl groups in tissue with Ellman's reagent. Anal Biochem. 1968;25(1):192-205.
• Lowry OH, Rosebrough NJ, Farr AL, Randall RJ. Protein measurement with the Folin phenol reagent. J Biol Chem. 1951;193(1):265-275.
• Livak KJ, Schmittgen TD. Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method. Methods. 2001;25(4):402-408.
• Oyagbemi AA, Omobowale TO, Asenuga ER, Ochigbo GO, Adejumobi AO, Adedapo AA, et al. Sodium arsenite-induced cardiovascular and renal dysfunction in rat via oxidative stress and protein kinase B (Akt/PKB) signaling pathway. Redox Report. 2017;22(6):467-477.
• Oyibo A, Gbadegesin MA, Odunola OA. Ethanol extract of Vitellaria paradoxa (Gaertn, F) leaves protects against sodium arsenite - induced toxicity in male wistar rats. Toxicol Rep. 2021;8:774-784.
• Mehrzadi S, Goudarzi M, Fatemi I, Basir Z, Malayeri A, Khalili H. Chrysin attenuates sodium arsenite-induced nephrotoxicity in rats by suppressing oxidative stress and inflammation. Tissue Cell. 2021;73:101657.
• Panghal A, Sathua KB, Flora SJS. Gallic acid and MiADMSA reversed arsenic induced oxidative/nitrosative damage in rat red blood cells. Heliyon. 2020;6(2):e03431.
• Bashir N, Ahmad SB, Rehman MU, Muzamil S, Bhat RR, Mir MUR, et al. Zingerone (4-(four-hydroxy-3-methylphenyl) butane-two-1) modulates adjuvant-induced rheumatoid arthritis by regulating inflammatory cytokines and antioxidants. Redox Rep. 2021;26(1):62-70.
• İleritürk M, Doğan T, Kandemir Ö. Investigation of the Effect of Berberine with Arginase Activity and Oxidant-Antioxidant Parameters on Bortezomib-Induced Spleen Injury in Rats. Kocatepe Vet J. 2021;14:6-15.
• İleritürk M, Doğan T, Statıcı E, Rutin’in Deltamethrin ile Mide Toksisitesi Geliştirilen Ratlarda Oksidatif Stres, Apoptoz ve İnflamasyon Parametreleri Üzerine Etkisinin Araştırılması. Fırat Üniversitesi Sağlık Bilimleri Veteriner Dergisi 2021;35(3): 158-165.
• Kandemir FM, Ileriturk M, Gur C. Rutin protects rat liver and kidney from sodium valproate-induce damage by attenuating oxidative stress, ER stress, inflammation, apoptosis and autophagy. Mol Biol Rep. 2022;49(7):6063-6074.
• Gur C, Kandemir FM. Evaluation of the Levels of Metalloproteinases as well as Markers of Oxidative Stress and Apoptosis in Lung Tissues After Malathion and Rutin Administrations to Rats. Turkish Journal of Nature and Science. 2022;11(3):51-57.
• Semis HS, Gur C, Ileriturk M, Kaynar O, Kandemir FM. Investigation of the anti-inflammatory effects of caffeic acid phenethyl ester in a model of lambda-Carrageenan-induced paw edema in rats. Hum Exp Toxicol. 2021;40(12_suppl):S721-S738.
• Gür C, Kandemir Ö, Kandemir FM. Evaluation of the Effects of Chrysin on Diclofenac-Induced Cardiotoxicity in Rats by the Markers of Oxidative Stress, Endoplasmic Reticulum Stress and Apoptosis. Kocatepe Vet J. 2022;15(2):151-160.
• Mirzaei M, Moosavi M, Mansouri E, Mohtadi S, Khodayar MJ. Diosmin exerts hepatoprotective and antihyperglycemic effects against sodium arsenite-induced toxicity through the modulation of oxidative stress and inflammation in mice. J Trace Elem Med Bio. 2023;78:127154.
• Semis HS, Gur C, Ileriturk M, Kandemir FM, Kaynar O. Evaluation of Therapeutic Effects of Quercetin Against Achilles Tendinopathy in Rats via Oxidative Stress, Inflammation, Apoptosis, Autophagy, and Metalloproteinases. Am J Sport Med. 2022;50(2):486-498.
• Ileriturk M, Benzer F, Aksu EH, Yildirim S, Kandemir FM, Dogan T, et al. Chrysin protects against testicular toxicity caused by lead acetate in rats with its antioxidant, anti-inflammatory, and antiapoptotic properties. J Food Biochem. 2021;45(2): e13593.
• Çomaklı S, İleritürk M, Manavoğlu Kirman E. Protective Effects of Rutin on Oxidative DNA Damage, NF-κB-Mediated Inflammation, and Apoptosis in Colistin-Induced Testicular Damage of Rats. Turkish Journal of Nature and Science. 2020;9(2):83-90.
• Akbari S, Amiri FT, Naderi M, Shaki F, Seyedabadi M. Sodium arsenite accelerates D-galactose-induced aging in the testis of the rat: Evidence for mitochondrial oxidative damage, NF-kB, JNK, and apoptosis pathways. Toxicology. 2022;470:153148.
• Gur C, Kandemir FM, Darendelioglu E, Caglayan C, Kucukler S, Kandemir O, et al. Morin protects against acrylamide-induced neurotoxicity in rats: an investigation into different signal pathways. Environ Sci Pollut R. 2021;28(36):49808-49819.
• Buyuklu M, Kandemir FM, Ozkaraca M, Set T, Bakirci EM, Topal E, et al. Benefical effects of lycopene against contrast medium-induced oxidative stress, inflammation, autophagy, and apoptosis in rat kidney. Hum Exp Toxicol. 2015;34(5):487-496.
• Ileriturk M, Kandemir O, Akaras N, Simsek H, Genc A, Kandemir FM. Hesperidin has a protective effect on paclitaxel-induced testicular toxicity through regulating oxidative stress, apoptosis, inflammation and endoplasmic reticulum stress. Reprod Toxicol. 2023;118:108369.