Dietilnitrozamin ile İndüklenen Tavşanlarda β-Karotenin Nitrik Oksit ve Malondialdehit Düzeylerine Etkisinin Araştırılması
Abstract
Nitrozaminler günlük yaşamda sıklıkla maruz kalınan karsinojenik bileşiklerdendir ve en bilindik üyesi dietilnitrozamin (DEN) olup, hepatik karsinoma neden olmaktadır. Dietilnitrozaminin erken dönem etkileri serbest radikal ve lipit peroksidasyonundaki artışı ile karakterizedir. β-karoten ise DEN’in hepatik hasarlarına karşı koruyucu etkileri olduğu düşünülen bir karotenoid türevidir. Bu çalışmada DEN toksikasyonuna karşı β-karoten uygulamasının serum nitrik oksit (NO) ve malondialdehit (MDA) değerleri üzerindeki etkilerinin belirlenmesi amaçlanmıştır. Bu amaçla 21 Yeni Zelanda ırkı tavşan 3 gruba ayrılmış ve ilk grup kontrol grubu olarak değerlendirilmiştir. Dietilnitrozamin toksikasyonu oluşturulan gruptaki hayvanlara (2. grup) intraperitonal yolla 100 mg/kg oranında DEN uygulanmıştır. Diğer gruptaki hayvanlara (3. grup) ise 100 mg/kg oranında DEN toksikasyonunun ardından 7 gün boyunca 2 mg/kg/gün oranında β-karoten oral olarak verilmiştir. Deneyin 1, 4 ve 7. günlerinde kan örnekleri alınarak serumlarından NO ve MDA değerleri belirlenmiştir. Nitrik oksit seviyeleri β-karoten uygulanan grupta yalnızca DEN uygulanan gruba kıyasla istatistiksel olarak azalmış (P<0.01) ve 1, 4 ve 7. günlerde benzer trendini korumuştur. Ancak 4 ve 7. günlerdeki MDA seviyeleri 1. gün MDA seviyelerine kıyasla artış göstermiştir. Sonuç olarak, β-karotenin DEN toksikasyonunda serum MDA ve NO seviyelerini istatistiksel olarak düşürdüğü görülmüştür. Bu yüzden, DEN’in toksik etkisine karşı β-karotenin NO ve MDA üzerinde koruyucu etkisinin olabileceği kanısına varılmıştır.
Keywords
References
- Kumar RS, Murugananthan G, Balasubramanian R. (2017). Anticarcinogenic potential of ethanol extract of Indigofera cordifolia Roth. (Fabales: Fabaceae) on diethylnitrosamine induced hepatocarcinogenesis in rats. Braz J Biol Sci. 4: 53-66.
- Zhang X, Cao L, Ji B, Li L, Qi Z, Ding S. (2020). Endurance training but not high-intensity interval training reduces liver carcinogenesis in mice with hepatocellular carcinogen diethylnitrosamine. Exp Gerontol. 133: 1-9.
- Bartsch H; Hietanen E, Malaveille C. (1989). Carcinogenic nitrosamines: Free radical aspects of their action. Free Radic Biol Med. 7: 637-644.
- Yamada K, Yamamiya I, Utsumi H. (2006). In vivo detection of free radicals induced by diethylnitrosamine in rat liver tissue. Free Radical Biol Med. 40: 2040-2046.
- Santos NP, Pereira IC, Pires MJ, et al. (2012). Histology, bioenergetics and oxidative stress in mouse liver exposed to N-diethylnitrosamine. In Vivo. 26: 921-929.
- Adebayo OA, Akinloye O, Adaramoye OA. (2020). Cerium oxide nanoparticles attenuate oxidative stress and inflammation in the liver of diethylnitrosamine-treated mice. Biol Trace Elem Res. 193: 214-225.
- Young AJ, Lowe GL. (2018). Carotenoids-antioxidant properties. Antioxidants (Basel). 7: 1-4.
- Ribeiro D, Freitas M, Silva AMS, Carvalho F, Fernandes E. (2018). Antioxidant and pro-oxidant activities of carotenoids and their oxidation products. Food Chem Toxicol. 120: 681-699.
- Radi R. (2018). Oxygen radicals, nitric oxide, and peroxynitrite: Redox pathways in molecular medicine. Proc Natl Acad Sci U S A. 115: 5839-5848.
- Atakisi E, Merhan O. (2017). Nitric Oxide Synthase and Nitric Oxide Involvement in Different Toxicities. In: Nitric Oxide Synthase-Simple Enzyme-Complex Roles. Saravi SSS (ed). pp. 525-542. InTechOpen, Croatia.
- Kamiloğlu NN, Kaçar C, Güven A, et al. (2017). Changes in lipid peroxidation, glutathione and fertility in tuj sheep after combined administration of vitamin A and E and passive immunization with testosterone antibodies. Kafkas Univ Vet Fak Derg. 23: 459-465.
- Aslankoç R, Demirci D, İnan Ü, et al. (2019). The role of antioxidant enzymes in oxidative stress - superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx). Med J SDU. 26: 362-369.
- Miranda KM, Espey MG, Wink DA. (2001). A rapid, simple spectrophotometric method for simultaneous detection of nitrate and nitrite. Nitric Oxide: Biol Chem. 5: 62-71.
- Yoshioka T, Kawada K, Shimada T, Mori M. (1979). Lipid peroxidation in maternal and cord blood and protective mechanism againist active-oxygen toxicity in the blood. Am J Obstet Gynecol. 135: 372-376.
- Bayraktar N, Gökçe R, Ergün O. (1998). Gıdalarda nitrat ve nitrit kalıntılarının insan sağlığı üzerine etkileri. Ekoloji. 28: 28-30.
- McCord JM. (1993). Human disease, free radicals, and the oxidant/antioxidant balance. Clin Biochem. 26: 351-357.
- Karabulut H, Gülay MŞ. (2016). Serbest radikaller. MAKÜ Sağ Bil Enst Derg. 4: 50-59.
- Süleyman H, Gül V, Erhan E. (2018). Oksidatif stres ve doku hasarı. Erzincan Tıp Derg. 1: 1-4.
- Merhan O. (2017). The Biochemistry and Antioxidant Properties of Carotenoids. In: Carotenoids. Cvetkovic D, Nikolic G (eds). pp. 51-66. InTechOpen, Croatia.
- Merhan O, Ozcan A, Atakisi E, Ogun M, Kükürt A. (2016). The effect of β-carotene on acute phase response in diethylnitrosamine given rabbits. Kafkas Univ Vet Fak Derg. 22: 533-537.
- Ertekin A, Türel İ, Oto G, Çelikezen FÇ, Yaşar S. (2008). Isırgan otunun dimetilbenzantrasen uygulanan tavşanlarda lipit peroksidasyonu, antioksidan maddeler ve nitrit-nitrat düzeyleri üzerine etkisi. Van Vet J. 2: 11-15.
- Latief U, Husain H, Ahmad R. (2018). β-Carotene supplementation ameliorates experimental liver fibrogenesis via restoring antioxidant status and hepatic stellate cells activity. J Func Foods. 49: 168-180.
- Atakişi E, Özcan A. (2005). Dietilnitrozamin verilen ratlarda omega-3 yağ asitlerinden zengin balık yağının koruyucu rolünün araştırılması. Türk Biyokimya Derg. 30: 279-284.
- Karaca EG, Bayşu Sözbilir N. (2007). Dietilnitrozamin verilen ratlarda alfa lipoik asidin koruyucu etkilerinin araştırılması. Kocatepe Tıp Derg. 7: 11-17.
- Agrawal A, Sharma M, Rai SK, Singh B, Tiwari M, Chandra R. (2008). The effect of the aqueous extract of the roots of asparagus racemosus on hepatocarcinogenesis initiated by diethylnitrosamine. Phytother Res. 22: 1175-1182.
- Önger ME, Genc H, Tan F. (2011). Effects of NOS inhibitors applied with cadmium sulphate on total lipid and protein quantities in central nervous system of rat (Wistar albino). J Exp Clin Med. 28: 175-181.
- Atakişi O, Atakişi E, Özcan A, Karapehlivan M, Kart A. (2013). Protective effect of omega-3 fatty acids on diethylnitrosamine toxicity in rats. Eur Rev Med Pharmaco. 17: 467-471.
- Liu J, Man S, Li J, Zhang Y, Meng X, Gao W. (2016). Inhibition of diethylnitrosamine-induced liver cancer in rats by Rhizoma paridis saponin. Environ Toxicol Pharmacol. 46: 103-109.
The Investigation of the Effect of β-Carotene on Nitric Oxide and Malondialdehyde Levels in Rabbits Induced with Diethylnitrosamine
Abstract
Nitrosamines are carcinogenic compounds that are frequently exposed in daily life and the most well-known member is diethylnitrosamine (DEN) which causing hepatic carcinoma. Early effects of DEN are characterized by the increase in free radical and lipid peroxidation. β-carotene is a carotenoid derivative thought to have protective effects against DEN's hepatic damage. In this study, it was aimed to determine the effects of β-carotene administration against DEN intoxication on serum nitric oxide (NO) and malondialdehyde (MDA) values. For this purpose, 21 New Zealand rabbits were divided into 3 groups and the first group was evaluated as the control group. 100 mg/kg of DEN was administered intraperitoneally to the animals in the group of DEN toxication (2. group). The animals in the other group (3. group) were given-carotene orally at a rate of 2 mg/kg/day for 7 days after 100 mg/kg DEN toxicity. Blood samples were taken on the 1st, 4th and 7th days of the experiment and NO and MDA values were determined from their serum. NO levels decreased in the β-carotene treated group compared to the DEN only group and maintained a similar trend on days 1, 4 and 7. However, MDA levels on days 4 and 7 increased compared to MDA levels on day 1. In conclusion, β-carotene was found to decrease serum MDA and NO levels in DEN intoxication. Therefore, β-carotene may have a protective effect on NO and MDA against toxic effects of DEN.
Keywords
References
- Kumar RS, Murugananthan G, Balasubramanian R. (2017). Anticarcinogenic potential of ethanol extract of Indigofera cordifolia Roth. (Fabales: Fabaceae) on diethylnitrosamine induced hepatocarcinogenesis in rats. Braz J Biol Sci. 4: 53-66.
- Zhang X, Cao L, Ji B, Li L, Qi Z, Ding S. (2020). Endurance training but not high-intensity interval training reduces liver carcinogenesis in mice with hepatocellular carcinogen diethylnitrosamine. Exp Gerontol. 133: 1-9.
- Bartsch H; Hietanen E, Malaveille C. (1989). Carcinogenic nitrosamines: Free radical aspects of their action. Free Radic Biol Med. 7: 637-644.
- Yamada K, Yamamiya I, Utsumi H. (2006). In vivo detection of free radicals induced by diethylnitrosamine in rat liver tissue. Free Radical Biol Med. 40: 2040-2046.
- Santos NP, Pereira IC, Pires MJ, et al. (2012). Histology, bioenergetics and oxidative stress in mouse liver exposed to N-diethylnitrosamine. In Vivo. 26: 921-929.
- Adebayo OA, Akinloye O, Adaramoye OA. (2020). Cerium oxide nanoparticles attenuate oxidative stress and inflammation in the liver of diethylnitrosamine-treated mice. Biol Trace Elem Res. 193: 214-225.
- Young AJ, Lowe GL. (2018). Carotenoids-antioxidant properties. Antioxidants (Basel). 7: 1-4.
- Ribeiro D, Freitas M, Silva AMS, Carvalho F, Fernandes E. (2018). Antioxidant and pro-oxidant activities of carotenoids and their oxidation products. Food Chem Toxicol. 120: 681-699.
- Radi R. (2018). Oxygen radicals, nitric oxide, and peroxynitrite: Redox pathways in molecular medicine. Proc Natl Acad Sci U S A. 115: 5839-5848.
- Atakisi E, Merhan O. (2017). Nitric Oxide Synthase and Nitric Oxide Involvement in Different Toxicities. In: Nitric Oxide Synthase-Simple Enzyme-Complex Roles. Saravi SSS (ed). pp. 525-542. InTechOpen, Croatia.
- Kamiloğlu NN, Kaçar C, Güven A, et al. (2017). Changes in lipid peroxidation, glutathione and fertility in tuj sheep after combined administration of vitamin A and E and passive immunization with testosterone antibodies. Kafkas Univ Vet Fak Derg. 23: 459-465.
- Aslankoç R, Demirci D, İnan Ü, et al. (2019). The role of antioxidant enzymes in oxidative stress - superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx). Med J SDU. 26: 362-369.
- Miranda KM, Espey MG, Wink DA. (2001). A rapid, simple spectrophotometric method for simultaneous detection of nitrate and nitrite. Nitric Oxide: Biol Chem. 5: 62-71.
- Yoshioka T, Kawada K, Shimada T, Mori M. (1979). Lipid peroxidation in maternal and cord blood and protective mechanism againist active-oxygen toxicity in the blood. Am J Obstet Gynecol. 135: 372-376.
- Bayraktar N, Gökçe R, Ergün O. (1998). Gıdalarda nitrat ve nitrit kalıntılarının insan sağlığı üzerine etkileri. Ekoloji. 28: 28-30.
- McCord JM. (1993). Human disease, free radicals, and the oxidant/antioxidant balance. Clin Biochem. 26: 351-357.
- Karabulut H, Gülay MŞ. (2016). Serbest radikaller. MAKÜ Sağ Bil Enst Derg. 4: 50-59.
- Süleyman H, Gül V, Erhan E. (2018). Oksidatif stres ve doku hasarı. Erzincan Tıp Derg. 1: 1-4.
- Merhan O. (2017). The Biochemistry and Antioxidant Properties of Carotenoids. In: Carotenoids. Cvetkovic D, Nikolic G (eds). pp. 51-66. InTechOpen, Croatia.
- Merhan O, Ozcan A, Atakisi E, Ogun M, Kükürt A. (2016). The effect of β-carotene on acute phase response in diethylnitrosamine given rabbits. Kafkas Univ Vet Fak Derg. 22: 533-537.
- Ertekin A, Türel İ, Oto G, Çelikezen FÇ, Yaşar S. (2008). Isırgan otunun dimetilbenzantrasen uygulanan tavşanlarda lipit peroksidasyonu, antioksidan maddeler ve nitrit-nitrat düzeyleri üzerine etkisi. Van Vet J. 2: 11-15.
- Latief U, Husain H, Ahmad R. (2018). β-Carotene supplementation ameliorates experimental liver fibrogenesis via restoring antioxidant status and hepatic stellate cells activity. J Func Foods. 49: 168-180.
- Atakişi E, Özcan A. (2005). Dietilnitrozamin verilen ratlarda omega-3 yağ asitlerinden zengin balık yağının koruyucu rolünün araştırılması. Türk Biyokimya Derg. 30: 279-284.
- Karaca EG, Bayşu Sözbilir N. (2007). Dietilnitrozamin verilen ratlarda alfa lipoik asidin koruyucu etkilerinin araştırılması. Kocatepe Tıp Derg. 7: 11-17.
- Agrawal A, Sharma M, Rai SK, Singh B, Tiwari M, Chandra R. (2008). The effect of the aqueous extract of the roots of asparagus racemosus on hepatocarcinogenesis initiated by diethylnitrosamine. Phytother Res. 22: 1175-1182.
- Önger ME, Genc H, Tan F. (2011). Effects of NOS inhibitors applied with cadmium sulphate on total lipid and protein quantities in central nervous system of rat (Wistar albino). J Exp Clin Med. 28: 175-181.
- Atakişi O, Atakişi E, Özcan A, Karapehlivan M, Kart A. (2013). Protective effect of omega-3 fatty acids on diethylnitrosamine toxicity in rats. Eur Rev Med Pharmaco. 17: 467-471.
- Liu J, Man S, Li J, Zhang Y, Meng X, Gao W. (2016). Inhibition of diethylnitrosamine-induced liver cancer in rats by Rhizoma paridis saponin. Environ Toxicol Pharmacol. 46: 103-109.
Details
| Primary Language | Turkish |
|---|---|
| Subjects | Veterinary Surgery |
| Journal Section | Research |
| Authors | |
| Publication Date | June 30, 2021 |
| Acceptance Date | April 6, 2021 |
| Published in Issue | Year 2021 Volume: 14 Issue: 1 |
