Sıçanlarda Sodyum Valproat ile İndüklenen Dalak Toksisitesinde Rutinin Antioksidan, Antiinflamatuvar ve Antiapoptotik Etkileri

Yıl 2023, , 138 - 144, 22.06.2023

Nurhan Akaras , Fatih Mehmet Kandemir , Hasan Şimşek , Cihan Gür , Serpil Aygörmez

https://doi.org/10.46810/tdfd.1299663

Cited By: 4

Öz

Amaç: Antiepileptik bir ilaç olan sodyum valproatın uzun süreli maruziyeti dokularda özellikle oksidatif stres ve inflamasyon artışına neden olarak toksik etki oluşturur. Rutin, birçok bitkide doğal olarak bulunan antioksidan, antiinflamatuvar ve antiapoptotik etkilere sahip bir flavanoiddir. Bu çalışmada, sodyum valproat kaynaklı dalak doku hasarı üzerine doğal bir antioksidan olan rutinin etkilerinin araştırılması amaçlanmıştır.
Gereç ve Yöntemler: 35 adet erkek sıçan kontrol, sodyum valproat, rutin, sodyum valproat+Rutin 50 ve sodyum valproat+Rutin 100 grupları olmak üzere 5 gruba ayrıldı. 14 gün boyunca 500 mg/kg dozda sodyum valproat uygulamasıyla birlikte 50 veya 100 mg/kg rutin uygulaması oral gavaj yolla yapıldı. 15. günde dalak dokuları alındı ve biyokimyasal yöntemler ile oksidatif stres, inflamasyon ve apoptotik parametrelerin analizi ve histolojik analizler yapıldı.
Bulgular: Dalak dokularında sodyum valproat kaynaklı oksidatif stres, inflamasyon ve apoptoz parametrelerin düzeyleri kontrol grubuna göre artmıştır (p<0,05). Rutin uygulamasıyla birlikte sodyum valproata bağlı tüm bu artış miktarlarında azalmalar meydana gelmiştir (p<0,05).
Sonuç: Dalak dokularında sodyum valproat maruziyetinin neden olduğu toksik etkiye karşı rutinin potansiyel koruyucu özelliklere sahip olduğu sonucuna varıldı.

Anahtar Kelimeler

Sodyum Valproat, Rutin, Oksidatif stres, İnflamasyon, Apoptoz, Dalak Toksisitesi

Antioxidant, Antiinflammatory, and Antiapoptotic Effects of Rutin in Spleen Toxicity Induced by Sodium Valproate in Rats

Öz

Aim: Long-term exposure to sodium valproate, an antiepileptic drug, causes toxic effects in tissues, especially by increasing oxidative stress and inflammation. Rutin is a flavanoid with antioxidant, anti-inflammatory and antiapoptotic effects found naturally in many plants. In this study, we aimed to investigate the effects of rutin, a natural antioxidant, on sodium valproate-induced spleen tissue damage.
Materials and Methods: 35 male rats were divided into 5 groups as control, sodium valproate, rutin, sodium valproate+Rutin 50 and sodium valproate+Rutin 100 groups. For 14 days, 500 mg/kg dose of sodium valproate and 50 or 100 mg/kg of rutin were administered by oral gavage. On day 15, spleen tissues were removed and biochemical methods, oxidative stress, inflammation and apoptotic parameters were analyzed and histologic analysis was performed.
Results: The levels of sodium valproate-induced oxidative stress, inflammation and apoptosis parameters increased in spleen tissues compared to the control group (p<0.05). With routine administration, all of these sodium valproate-induced increases were decreased (p<0.05).
Conclusion: It was concluded that rutin has potential protective properties against the toxic effect caused by sodium valproate exposure in spleen tissues.

Anahtar Kelimeler

Sodium Valproate, Rutin, Oxidative stress, Inflammation, Apoptosis, Spleen Toxicity

Kaynakça

• 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):6063-74.
• Phillips A, Bullock T, Plant N. Sodium valproate induces apoptosis in the rat hepatoma cell line, FaO. Toxicology. 2003;192(2-3):219-27.
• Parikh SK, Silberstein SD. Current status of antiepileptic drugs as preventive migraine therapy. Curr Treat Options Neurol. 2019;21(4):16.
• de Campos Vidal B, Mello MLS. Sodium valproate (VPA) interactions with DNA and histones. Int J Biol Macromol. 2020;163, 219-231.
• Khani S, Hejazi SA, Yaghoubi M, Sharifipour E. Comparative study of magnesium, sodium valproate, and concurrent magnesium-sodium valproate therapy in the prevention of migraine headaches: a randomized controlled double-blind trial. J Headache Pain. 2021;22(1), 1-10.
• Patel AR, Nagalli S. Valproate toxicity. [Updated 2023 May 17]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2023 May-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK560898/
• Mei X, Wu HC, Ruan M, Cai LR. Acute liver failure with thrombotic microangiopathy due to sodium valproate toxicity: A case report. World J Clin Cases. 2021;9(17):4310-17.
• Sharma A, Sinha S, Narang A, Chouhan DK, Gupta S. Waddling Gait: A complication of valproate therapy and a thought beyond vitamin d deficiency. Sultan Qaboos Univ Med J. 2020;20(1):e104-e108.
• Ola OS, Adewole KE. Anticlastogenic and hepatoprotective effects of kolaviron on sodium valproate-ınduced oxidative toxicity in wistar rats. Egyptian Journal of Basic and Applied Sciences. 2021;8(1):167-79.
• Ayna A, Darendelioğlu E. Evaluation of the biological activities of royal jelly on prostate and breast cancer cells. Türk Doğa ve Fen Dergisi. 2022;11(3):166-70.
• Ayna A. Apoptotic effects of beta-carotene, alpha-tocopherol and ascorbic acid on PC-3 prostate cancer cells. Hacettepe Journal of Biology and Chemistry. 2020;48(3):211-18.
• Varışlı B, Caglayan C, Kandemir FM, Gür C, Ayna A, Genç A, et al. Chrysin mitigates diclofenac-induced hepatotoxicity by modulating oxidative stress, apoptosis, autophagy and endoplasmic reticulum stress in rats. Mol Biol Rep. 2023;50(1),433-42.
• Caglayan C, Kandemir FM, Darendelioğlu E, Yıldırım S, Kucukler S, Dortbudak MB. Rutin Ameliorates Mercuric Chloride-Induced Hepatotoxicity in Rats via İnterfering with Oxidative Stress, Inflammation And Apoptosis. J Trace Elem Med Biol 2019;56:60-68
• Kandemir FM, Caglayan C, Aksu EH, Yildirim S, Kucukler S, Gur C, et al. Protective effect of rutin on mercuric chloride-ınduced reproductive damage in male rats. Andrologia 2020;52(3):e13524.
• Caglayan C, Kandemir FM, Yildirim S, Kucukler S, Eser G. Rutin protects mercuric chloride-ınduced nephrotoxicity via targeting of aquaporin 1 level, oxidative stress, apoptosis and inflammation in rats. J Trace Elem Med Biol. 2019;54:69-78.
• Çelik H, Kandemir FM, Caglayan C, Özdemir S, Çomaklı S, Kucukler S, et al. Neuroprotective effect of rutin against colistin-ınduced oxidative stress, ınflammation and apoptosis in rat brain associated with the CREB/BDNF expressions. Mol Biol Rep 2020;47(3):2023-34.
• Kandemir FM, Ozkaraca M, Yildirim BA, Hanedan B, Kirbas A, Kilic, et al. Rutin attenuates gentamicin-induced renal damage by reducing oxidative stress, inflammation, apoptosis, and autophagy in rats. Renal failure. 2015;37(3),518-525.
• Placer ZA, Cushman LL, Johnson BC. Estimation of product of lipid peroxidation (malonyl dialdehyde) in biochemical systems. Anal Biochem 1966;16(2):359–64.
• 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;105:121–26.
• Lawrence RA, Burk RF. Glutathione peroxidase activity in selenium-deficient rat liver. Biochem Biophys Res Commun. 1976;71(4)952–58.
• 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):265–75.
• Lo U, Selvaraj V, Plane JM, Chechneva OV, Otsu K, Deng W. p38α (MAPK14) critically regulates the immunological response and the production of specific cytokines and chemokines in astrocytes. Scientific reports. 2014;4(1),7405.
• Ardianto C, Wardani HA, Nurrahmi N, Rahmadi M, Khotib J. Alpha-lipoic acid ameliorates sodium valproate-induced liver injury in mice. Vet World. 2020;13(5):963-66.
• Işık M, Demir Y, Kırıcı M, Demir R, Şimşek F, Beydemir Ş. Changes in the anti-oxidant system in adult epilepsy patients receiving anti-epileptic drugs. Arch Physiol Biochem 2015;121(3):97-102.
• Beydemir Ş, Demir Y. Antiepileptic drugs: Impacts on human serum paraoxonase-1. J Biochem Mol Toxicol. 2017;31(6).
• Mozūraitė R, Stakišaitis D, Didžiapetrienė J, Balnytė I, Matusevičius P, Valančiūtė A. Gender-related rat gl. thymus and spleen changes under the influence of Sodium valproate. In Baltic Morphology VII Scientific Conference" Morphological Sciences in the Experimental and Clinical Medicine": November 7-9, 2013, Rīga, Latvia: abstract book/Rīga Stradiņš University (RSU). [Institute of Anatomy and Anthropology]; Committee: Māra Pilmane [et al.]. Rīga: Rīga Stradiņš University, 2013.
• Yardim A, Gur C, Comakli S, Ozdemir S, Kucukler S, Celik H, et al. Investigation of the effects of berberine on bortezomib-induced sciatic nerve and spinal cord damage in rats through pathways involved in oxidative stress and neuro-inflammation. Neurotoxicology. 2022;89:127-39.
• Gao Y, Jiang D, Wang C, An G, Zhu L, Cui C. Comprehensive analysis of metabolic changes in male mice exposed to sodium valproate based on GC-MS analysis. Drug Des Devel Ther. 2022:1915-30.
• 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.
• Palabıyık E, Sulumer AN, Uguz H, Avcı B, Askın S, Askın H, et al. Assessment of hypolipidemic and anti-inflammatory properties of walnut (Juglans regia) seed coat extract and modulates some metabolic enzymes activity in triton WR-1339-induced hyperlipidemia in rat kidney, liver, and heart. J Mol Recognit. 2023;36(3):e3004.
• Korkmaz IN, Türkeş C, Demir Y, Öztekin A, Özdemir H, Beydemir Ş. Biological evaluation and in silico study of benzohydrazide derivatives as paraoxonase 1 inhibitors. J Biochem Mol Toxicol. 2022;36(11):e23180.
• 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.
• Ömür AD, Kandemir FM, Yıldırım BA. Protective effect of dandelion (Taraxacum officinale) extract Against gentamicin-induced reproductive damage in male rats. Kafkas Univ. Vet. Fak. 2016;22:929-36.
• Özaslan MS, Demir Y, Aksoy M, Küfrevioğlu ÖI, Beydemir Ş. Inhibition effects of pesticides on glutathione-S-transferase enzyme activity of Van Lake fish liver. J Biochem Mol Toxicol. 2018;32(9):e22196.
• Türkeş C, Kesebir AÖ, Demir Y, Küfrevioğlu Öİ, Beydemir Ş. Calcium channel blockers: The effect of glutathione S‐Transferase enzyme activity and molecular docking studies. ChemistrySelect. 2021;6(40):11137-43.
• Türkeş C, Demir Y, Beydemir Ş. Infection medications: Assessment in‐vitro glutathione S‐Transferase inhibition and molecular docking study. ChemistrySelect. 2021;6(43):11915-24.
• Aksu EH, Kandemir FM, Özkaraca M, Ömür AD, Küçükler S, Çomaklı S. Rutin ameliorates cisplatin‐induced reproductive damage via suppression of oxidative stress and apoptosis in adult male rats. Andrologia. 2017;49(1):e12593.
• Caglayan C, Kandemir FM, Darendelioğlu E, Küçükler S, Ayna A. Hesperidin protects liver and kidney against sodium fluoride-induced toxicity through anti-apoptotic and anti-autophagic mechanisms. Life Sciences. 2021;281:119730.
• Caglayan C, Kandemir FM, Ayna A, Gür C, Küçükler S, Darendelioğlu E. Neuroprotective effects of 18β-glycyrrhetinic acid against bisphenol A-induced neurotoxicity in rats: involvement of neuronal apoptosis, endoplasmic reticulum stress and JAK1/STAT1 signaling pathway. Metab Brain Dis. 2022;37(6):1931-40.
• Yardım A, Kandemir FM, Çomaklı S, Özdemir S, Caglayan C, Kucukler S, et al. Protective effects of curcumin against paclitaxel-induced spinal cord and sciatic nerve injuries in rats. Neurochem Res. 2021;46,379-95.
• Şimşek H, Demiryürek Ş, Demir T, Atabay HD, Çeribasi AO, Bayraktar R, et al. Assessment of expressions of Bcl-XL, b-FGF, Bmp-2, Caspase-3, PDGFR-α, Smad1 and TGF-β1 genes in a rat model of lung ischemia/reperfusion. Iran J Basic Med Sci. 2016;19(2):209-14.
• Simsek H, Akaras N. Acacetin ameliorates acetylsalicylic acid-induced gastric ulcer in rats by interfering with oxidative stress, inflammation, and apoptosis. Int J Med Biochem. 2023;6(2):96-103.
• Kucukler S, Caglayan C, Darendelioğlu E, Kandemir FM. Morin attenuates acrylamide-induced testicular toxicity in rats by regulating the NF-κB, Bax/Bcl-2 and PI3K/Akt/mTOR signaling pathways. Life Sciences. 2020;261:118301.
• Şimşek H, Akaras N, Gür C, Küçükler S, Kandemir FM. Beneficial effects of Chrysin on Cadmium-induced nephrotoxicity in rats: Modulating the levels of Nrf2/HO-1, RAGE/NLRP3, and Caspase-3/Bax/Bcl-2 signaling pathways. Gene. 2023;875:147502.