Artemisinin Uygulamasının, Pentilentetrazol ile İndüklenen Farelerin Karaciğer ve Böbrek Dokusunda Total Oksidan/Antioksidan ve Oksidatif Stres İndeksi Üzerine Etkisinin Araştırılması

Year 2022, Volume: 33 Issue: 3, 117 - 121, 29.11.2022

Yılmaz Koçak

https://doi.org/10.36483/vanvetj.1171405

Abstract

Bu çalışma, pentilentetrazol (PTZ) uygulanan farelerde oluşabilecek oksidatif strese karşı artemisinin ön tedavisinin farelerin karaciğer ve böbrek dokularında toplam oksidan (TOS)/antioksidan (TAS) ve oksidatif stres indeksi (OSI) düzeylerindeki değişiklikleri araştırmak için tasarlanmıştır. Çalışmada İsviçre albino fareleri (Erkek) (n=42) kullanıldı. Fareler altı gruba ayrıldı ve her grupta yedi hayvan (n=7) vardı: (1) Kontrol (C) /salin Grubu, (2) PTZ (35 mg/kg.) Grubu, (3) Valproat (VPA) (100 mg/kg) + PTZ Grubu, (4) Artemisinin (ART) (30 mg/kg) + PTZ Grubu, (5) ART (60 mg/kg) + PTZ Grubu, (6) ART (120 mg/kg) + PTZ Grubu. Fareler, intraperitoneal (ip) olarak enjeksiyonlar uygulandı. Uygulamalardan sonra hayvanlar 30 dakika boyunca nöbetler için gözlendi. Deneyin son gününde (26. gün) farelere PTZ yükleme dozu (75 mg/kg) uygulandı ve ardından hayvanlar sakrifiye edildi. Karaciğer ve böbrek dokusunda TAS, TOS ve OSI düzeyleri ölçüldü. PTZ, karaciğer ve böbrek dokusunda TOS'u artırdı ve TAS'ı azalttı. ART, artan dozlarda karaciğer dokusunda TAS'ı önemli ölçüde artırdı ve TOS'u azalttı (p<0.05). ART böbrek dokusunda çok etkili değildi. Ancak böbrek dokusundaki TAS düzeyleri VPA diğer gruplarla karşılaştırıldığında anlamlı olarak yüksekti (p<0.05). Bu çalışmada, PTZ kaynaklı oksidatif stresin, periferik dokularda glutamat reseptörlerinin aktivasyonundan kaynaklanabileceği varsayılabilir. ART, PTZ'nin neden olduğu oksidatif stres ve hipoksiye bağlı karaciğer hasarına karşı koruyucu bir etkiye sahip olabilir. Bu etki, ART'nin antioksidan kapasitesine bağlı olabilir.

Keywords

Artemisinin, Böbrek, Karaciğer, Oksidatif stres, Pentilentetrazol

Investigation of The Effect of Artemisinin Administration on Total Oxidant/Antioxidant and Oxidative Stress-Index in The Liver and Kidney Tissue of Pentylenetetrazole-Induced Mice

Abstract

This study was designed to investigate the changes in total oxidant (TOS)/antioxidant (TAS) and oxidative stress index (OSI) levels in liver and kidney tissues of mice pre-treatment of artemisinin against oxidative stress that may occur in mice administered pentylenetetrazole (PTZ). Swiss albino mice (Male) (n=42) were used in the study. The mice were divided into six groups and each group had seven animals (n=7): (1) Control (C) /saline Group, (2) PTZ (35 mg/kg) Group, (3) Valproate (VPA) (100 mg/kg) + PTZ Group, (4) Artemisinin (ART) (30 mg/kg) + PTZ Group, (5) ART (60 mg/kg) + PTZ Group, (6) ART (120 mg/kg) + PTZ Group. Mice received injections intraperitoneally (ip). After the treatments, the animals were observed for seizures for 30 minutes. On the last day (day 26) of the experiment, the PTZ loading dose (75 mg/kg) was administered to the mice and then the animals were sacrificed. TAS, TOS and OSI levels were measured in liver and kidney tissue. PTZ increased TOS and decreased TAS in liver and kidney tissue. ART significantly increased TAS and decreased TOS in liver tissue at increasing doses (p<0.05). ART was not very effective in kidney tissue. However, TAS levels in kidney tissue were significantly higher when VPA was compared with other groups (p<0.05). In this study, it can be assumed that PTZ-induced oxidative stress may be due to the activation of glutamate receptors in peripheral tissues. ART may have a protective effect against liver damage due to PTZ-induced oxidative stress and hypoxia. This effect may be due to the antioxidant capacity of ART.

Keywords

Artemisinin, Kidney, Liver, Oxidative stress, Pentylenetetrazole

Supporting Institution

The authors declared thatthis study has received no financial support

References

• Ahmed-Laloui H, Zaak H, Rahmani A, et al (2022). Assessment of artemisinin and antioxidant activities of three wild Artemisia species of Algeria. Nat Prod Res, 1-9.
• Akbas SH, Yegin A, Ozben T (2005). Effect of pentylenetetrazol-induced epileptic seizure on the antioxidant enzyme activities, glutathione and lipid peroxidation levels in rat erythrocytes and liver tissues. Clin Biochem, 38 (11), 1009–1014. Armaǧan A, Kutluhan S, Yilmaz M, et al (2008). Topiramate and Vitamin E Modulate Antioxidant Enzyme Activities, Nitric Oxide and Lipid Peroxidation Levels in Pentylenetetrazol-Induced Nephrotoxicity in Rats. Basic Clin Pharmacol Toxicol, 103 (2), 166–170.
• Bhatti JS, Sehrawat A, Mishra J, et al (2022). Oxidative stress in the pathophysiology of type 2 diabetes and related complications: Current therapeutics strategies and future perspectives. Free Radic Biol Med, 184, 114–134.
• Bulduk B (2022). Effect of chitosan application on lung tissue in rats with experimental fluorine toxicity. J Health Sci Med, 5 (4), 969-972.
• Buyukuslu N, Yigitbasi T (2015). Reactive Oxygen Species and Oxidative Stress in Obesity. Clin Exp Health Sci, 5 (3), 197.
• Cengiz M, Yüksel A, Seven M (2000). The Effects of Carbamazepin and Valporoic Acid on the Erythrocyte Glutathione, Glutathione Peroxidase, Superoxide Dismutase and Serum Lipid Peroxidation in Epileptic Children. Pharmacol Res, 41 (4), 423–425.
• Cikman O, Ozkan A, Aras AB, et al (2014). Radioprotective effects of nigella sativa oil against oxidative stress in liver tissue of rats exposed to total head irradiation. J Invest Surg, 27 (5), 262–266.
• Decell MK, Gordon JB, Silver K, et al (1994). Fulminant hepatic failure associated with status epilepticus in children: Three cases and a review of potential mechanisms. Intensive Care Med, 20 (5), 375–378.
• Dehkordi FM, Kaboutari J, Zendehdel M, Javdani M (2019). The antinociceptive effect of artemisinin on the inflammatory pain and role of GABAergic and opioidergic systems. Korean J Pain, 32 (3), 160-167.
• Demirci-Çekiç S, Özkan G, Avan AN, et al (2022). Biomarkers of Oxidative Stress and Antioxidant Defense. J Pharm Biomed Anal, 209, 114477.
• Dillioglugil MO, Kir HM, Demir C, et al (2010). Effect of pentylenetetrazole and sound stimulation induced single and repeated convulsive seizures on the MDA, GSH and NO levels, and SOD activities in rat liver and kidney tissues. Brain Res Bull, 83 (6), 356–359.
• Egwu CO, Pério P, Augereau JM, et al (2022). Resistance to artemisinin in falciparum malaria parasites: A redox-mediated phenomenon. Free Radic Biol Med, 179, 317–327.
• Erel O (2004). A novel automated method to measure total antioxidant response against potent free radical reactions. Clin Biochem, 37 (2), 112–119.
• Erel O (2005). A new automated colorimetric method for measuring total oxidant status. Clin Biochem, 38 (12), 1103–1111.
• Goudarzi R, Zamanian G, Partoazar A, et al (2020). Novel effect of Arthrocen (avocado/soy unsaponifiables) on pentylenetetrazole-induced seizure threshold in mice: Role of GABAergic pathway. Epilepsy Behav, 104, 1-5.
• Hamed SA (2017). The effect of antiepileptic drugs on the kidney function and structure. Expert Rev Clin Pharmacol, 10 (9), 993–1006.
• Ichai P, Huguet E, Guettier C, et al (2003). Fulminant hepatitis after grand mal seizures: Mechanisms and role of liver transplantation. Hepatol, 38 (2), 443–451.
• Ilhan A, Gurel A, Armutcu F, Kamıslı S, Iraz M (2005). Antiepileptogenic and antioxidant effects of Nigella sativa oil against pentylenetetrazol-induced kindling in mice. Neuropharm, 49 (4), 456–464.
• Jin O. Zhang H, Gu Z, et al (2009). A Pilot Study of the Therapeutic Efficacy and Mechanism of Artesunate in the MRL/lpr Murine Model of Systemic Lupus Erythematosus. Cell Mol Immunol, 6 (6), 461–467.
• Kapucu A, Kaptan Z, Akgun Dar K, kaleler İ, Üzüm G (2021). Effects of Erythropoietin Pretreatment on Liver, Kidney, Heart Tissue in Pentylentetrazol-Induced Seizures; Evaluation in Terms of Oxidative Markers, Prolidase and Sialic Acid. J Ist Faculty Med, 84 (4), 464–471.
• Kiasalari Z, Khalili M, Roghani M, Heidari H, Azizi Y (2013). Antiepileptic and Antioxidant Effect of Hydroalcoholic Extract of Ferula Assa Foetida Gum on Pentylentetrazole- induced Kindling in Male Mice. Basic Clin Neurosci, 4 (4), 299- 306.
• Kim W, Choi WJ, Lee S, et al (2014). Anti-inflammatory, Antioxidant and Antimicrobial Effects of Artemisinin Extracts from Artemisia annua L. Korean J Physiol Pharmacol, 19 (1), 21–27.
• Kiss E, Kins S, Zöller Y, et al (2021). Artesunate restores the levels of inhibitory synapse proteins and reduces amyloid-β and C-terminal fragments (CTFs) of the amyloid precursor protein in an AD-mouse model. Mol Cell Neurosci, 113, 103624.
• Kurt S, Eşki F, Mis L (2022). Monitoring of oxidative stress and TNF-α status during the healing process in hair goats with metritis. TJVR, 6 (1), 15–18.
• Li D, Bai X, Jiang Y, Cheng Y (2021). Butyrate alleviates PTZ-induced mitochondrial dysfunction, oxidative stress and neuron apoptosis in mice via Keap1/Nrf2/HO-1 pathway. Brain Res Bull, 168, 25–35.
• Lowry OH (1951). Protein measurement with the Folin phenol reagent. J Biol Chem, 193, 265-275.
• Lu L (2002). Study on effect of Cordyceps sinensis and artemisinin in preventing recurrence of lupus nephritis. Chin J Integr Med, 2 (3), 169–171.
• Lüttjohann A, Fabene PF, van Luijtelaar G (2009). A revised Racine’s scale for PTZ-induced seizures in rats. Physiol & Behav, 98 (5), 579–586.
• Obay BD, Taşdemir E, Tümer C, Bilgin HM (2008). Dose-dependent effects of ghrelin on pentylenetetrazole-induced oxidative stress in a rat seizure model. Peptides, 29 (3), 448–455.
• Rodrigues AD, Scheffel TB, Scola G, et al (2013). Purple grape juices prevent pentylenetetrazol-induced oxidative damage in the liver and serum of Wistar rats. Nutr Res, 33 (2), 120–125.
• Sudha K, Rao AV, Rao A (2001). Oxidative stress and antioxidants in epilepsy. Clin Chim Acta, 303 (1–2), 19–24. Tousson E, Keshta ATH, Hussein Y, Fekry RM, Abo-Ghaneima WK (2019). Fekry, R. M., & Abo-Ghaneima, W. K. (2019). Renal Protective Effect of Ginkgo biloba and L-carnitine Extracts against Pentylenetetrazol Induced Toxicity, Oxidative Stress, Injury and Proliferation Alternation in Epileptic Rats. Annu Rev Cancer Biol, 32 (2), 1–13.
• Ulusu NN, Aydemir D, Oztasci B, Barlas N (2020). Influence of the butylparaben administration on the oxidative stress metabolism of liver, kidney and spleen. Turk J Biochem, 45 (6), 689–694.
• Uma Devi P, Kolappa Pillai K, Vohora D (2006). Modulation of pentylenetetrazole-induced seizures and oxidative stress parameters by sodium valproate in the absence and presence of N-acetylcysteine. Fundam Clin Pharmacol, 20 (3), 247–253.
• Xia M, Liu D, Liu Y, Liu H (2006). The Therapeutic Effect of Artemisinin and Its Derivatives in Kidney Disease. Front Pharmacol, 11, 380.
• Xu G, Huang YL, Li P, Guo HM, Han XP (2017). Neuroprotective effects of artemisinin against isoflurane-induced cognitive impairments and neuronal cell death involve JNK/ERK1/2 signaling and improved hippocampal histone acetylation in neonatal rats. J Pharm Pharmacol, 69 (6), 684–697.
• Xu Y, Fan Q (2022). Relationship between chronic hypoxia and seizure susceptibility. CNS Neurosci Ther, 1–17.