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Radyasyona Maruz Kalan Ratlarda Oksidan/Antioksidan Durum Üzerine N-Asetilsistein’in Etkisi

Year 2020, Volume: 17 Issue: 3, 221 - 226, 01.12.2020
https://doi.org/10.32707/ercivet.828349

Abstract

N-Asetilsistein (NAC) hem güçlü bir antioksidan, hemde glutatyon prekürsörüdür. Radyasyona maruz kalan ratların bazı dokularındaki oksidan/antioksidan durum üzerine NAC’ın etkisi araştırıldı. Yirmi bir rat üç gruba bölündü; 1. grup kontrol grubu. 2. grup radyasyon grubu; serum fizyolojik üç gün i.p. verildikden sonra 9 Gy gamma radyasyon uygulandı. Üçüncü grup radyasyon + NAC grubu; NAC, 300 mg/kg canlı ağırlık i.p. olarak üç gün süreyle verildi ve sonra aynı dozda radyasyon uygulandı. Radyasyon sonucu, ratların karaciğer, böbrek ve beyin dokularında malondial-dehit (MDA)'de önemli artış saptandı (P<0.05). Tüm dokulardaki glutatyon peroksidaz (GSH-Px) aktivitesi ve sadece karaciğer süperoksit dismutaz (SOD) aktivitesi azaldı (P˂0.01), böbrek ve ovaryum dokularında glutatyon (GSH) düzeyleri önemli olarak arttı (P< 0.001). N-Asetilsistein ilavesinin radyasyon sonucu böbrek ve beyindeki artmış MDA seviyelerini normal seviyeye ulaştırırken (P<0.05), karaciğer dokusunda artan MDA seviyelerini normal seviyeye (P˂0001) getiremediği belirlendi. N-Asetilsistein ilavesi hem kontrol hemde radyasyon uygulanan gruba gore; kara-ciğer, kalp, dalak, beyin ve ovaryum dokularının GSH seviyelerinde önemli artışa, böbrek dokusunda radyasyon uygu-lanan gruba göre önemli azalmaya sebep oldu (P˂0.001). N-Asetilsistein ilavesiyle dalak GSH-Px aktivitesinde, kalp ve ovaryum SOD aktivitesinde kontrol ve radyasyon uygulanan gruba göre önemli azalma tespit edildi (P˂0.05). N-Asetilsistein ilavesiyle artan GSH’un radyasyon sonucu oluşan oksidatif stresi azaltmada rol alan ana antioksidan olduğu söylenebilir. Doku MDA değerleri incelendiğinde, NAC ilavesinin böbrek ve beyini radyasyonun neden olduğu oksidatif hasardan korumasına rağmen, karaciğer için yetersiz kalabileceği düşünülebilir.

References

  • Aruoma OI, Halliwell B, Hoey BM, Butler J. The anti-oxidant action of N-acetylcysteine: its reaction with hydrogen peroxide, hydroxyl radical, super-oxide, and hypochlorous acid. Free Radic Biol Med 1989; 6: 593-7.
  • Ashry OM, Hussein EM, Abd El-Azime AS. Restora-tive role of persimmon leaf (Diospyros kaki) to gamma irradiation-induced oxidative stress and tissue injury in rats. Int J Radiat Biol 2017; 93(3): 324-9.
  • Benkovica V, Knezevica AH, Dikic D, Lisicic D, Orsolic N, Basic I, Kosalec I, Kopjar N. Radiopro-tective effects of propolis and quercetin in gamma-irradiated mice evaluated by the alkaline comet assay. Phytomedicine 2008; 15: 851-8.
  • Burgunder JM, Varriale A, Lauterburg BH. Effect of N-acetylcysteine on plasma cysteine and glutathi-one following paracetamol administration. Eur J Clin Pharmacol 1989; 36:127-31.
  • Comporti M. Lipid peroxidation and cellular damage in toxic liver injury. Lab Invest 1985; 53: 599-623.
  • Cosar R, Yurut-Caloglu V, Eskiocak S, Ozen A, Al-taner S, Ibis K, Turan N, Denizli B, Uzal C, Saynak M, Parlar S, Caloglu M, Uregen B, Kocak Z. Radiation-induced chronic oxidative renal dam-age can be reduced by amifostine. Med Oncol 2012; 29 (2):768-75.
  • De Ferreyra E, Villarruel M, Fernandez G, De Fenos O, Bernacchi A, De Castro C, Castro J. Further studies on the mechanism of the late protective effects of phenylmethylsulfonyl fluoride on carbon tetrachloride-induced liver necrosis. Exp Mol Pathol 1989; 5: 253-69.
  • Demir EO, Cakmak GK, Bakkal H, Turkcu UO, Kan-demir N, Demir AS, Tascılar O. N-acetyl-cysteine improves anastomotic wound healing after radio-therapy in rats. J Invest Surg 2011; 24 (4): 151-8.
  • Demirkol O, Adams C, Ercal N. Biologically important thiols in various vegetables and fruits. J Agric Food Chem 2004; 52 (26): 8151-4.
  • Duthie SJ, Ma A, Ross MA, Collins AR. Antioxidant supplementation decreases oxidative DNA dama-ge in human lymphocytes. Cancer Res 1996; 56 (6): 1291-5.
  • Ekici K, Temelli O, Parlakpinar H, Samdanci E, Polat A, Beytur A, Tanbek K, Ekici C, Dursun IH. Bene-ficial effects of aminoguanidine on radiotherapy-induced kidney and testis injury. Andrologia 2016; 48 (6): 683-92.
  • El-Gazzar MG, Zaher NH, El-Hossary EM, Ismail AFM. Radio-protective effect of some new curcu-min analogues. J Photochem Photobiol B 2016; 162: 694-702.
  • Gulbahar O, Aricioglu A, Akmansu M, Turkozer Z. Effects of radiation on protein oxidation and lipid peroxidation in the brain tissue. Transplant Proc 2009; 41 (10): 4394-6.
  • Hsu CC, Huang CN, Hung YC, Yin MC. Five cysteine containing compounds have antioxidative activity in Balb/cA mice. J Nutr 2004; 134: 149-52.
  • Karami M, Asri-Rezaei S, Dormanesh B, Nazariza-deh A. Comparative study of radioprotective ef-fects of selenium nanoparticles and sodium sele-nite in irradiation-induced nephropathy of mice model. Int J Radiat Biol 2018; 94 (1): 17-27.
  • Khattab HAH, Abdallah IZA, Yousef FM, Huwait EA. Efficiency of borage seeds oil against gamma irradiation-induced hepatotoxicity in male rats: possible antioxidant activity. Afr J Tradit Comple-ment Altern Med 2017; 14(4): 169-79.
  • Kilciksiz S, Demirel C, Erdal N, Gürgül S, Tamer L, Ayaz L, Ors Y. The effect of N-acetylcysteine on biomarkers for radiation-induced oxidative dam-age in a rat model. Acta Med Okayama 2008; 62(6): 403-9.
  • Lawenda BD, Kelly KM, Ladas EJ, et al. Should sup-plemental antioxidant administration be avoided during chemotherapy and radiation therapy? J Natl Cancer 2008; 100 (11): 773-83.
  • Lawrence RA, Burk RF. Glutathione peroxidase ac-tivity in selenium-deficient rat liver. Biochem Bio-phys Res Commun 1976; 71 (4): 952-8.
  • Liu Y, Zhang H, Zhang L, Zhou Q, Wang X, Long., Dong T, Zhao W. Antioxidant N-acetylcysteine attenuates the acute liver injury caused by X-ray in mice. Eur J Pharmacol 2007; 575 (1-3): 142-8.
  • Lowry OH, Rosebrough NJ, Farr AL, Randall RJ. Protein measurement with folin phenol reagent. J Biol Chem 1951; 193 (1): 265-75.
  • Mansour HH, Hafez HF, Fahmy NM, Hanafi N. Pro-tective effect of N-acetylcysteine against radiation induced DNA damage and hepatic toxicity in rats. Biochem Pharmacol 2008; 75 (3): 773-80.
  • Neal R, Matthews RH, Lutz P, Ercal N. Antioxidant role of N-acetyl cysteine isomers following high dose irradiation. Free Radic Biol Med 2003, 34 (6): 689-95.
  • Patton S, Kurtz GW. 2-Thiobarbituric acid as a rea-gent for detecting milk fat oxidation. J Dairy Sci 1951; 34: 669-74.
  • Placer ZA, Cushman LL, Johnson BC. Estimation of product of lipid peroxidation (malonyldialdehyde) in biochemical systems. Anal Biochem 1966; 16 (2): 359-64.
  • Radwan RR, Mohamed HA. Nigella sativa oil modula-tes the therapeutic efficacy of mesenchymal stem cells against liver injury in irradiated rats. J Pho-tochem Photobiol B 2018; 178: 447-56.
  • Scibior D, Skrzycki M, Podsiad M, Czeczot H. Gluta-thione level and glutathione-dependent enzyme activities in blood serum of patients with gastroin-testinal tract tumors. Clin Biochem 2008; 41: 852-8.
  • 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.
  • Sies H. Strategies of antioxidant defense. Eur J Bio-chem 1993; 215 (2): 213-9.
  • Simsek Y, Gurocak S, Turkoz Y, Akpolat N, Celik O, Ozer A, Yılmaz E, Turhan U, Ozyalin F. Ameliora-tive effects of resveratrol on acute ovarian toxicity induced by total body irradiation in young adult rats. J Pediatr Adolesc Gynecol 2012; 25 (4): 262-6.
  • Sun Y, Oberley WL, Li Y. A simple method for clinical assay of superoxide dismutase. Clin Chem 1988; 34: 497-500.
  • Thomas SH. Paracetamol (acetaminophen) poison-ing. Pharmacol Ther 1993; 60 (1): 91-120.
  • Tosetti F, Ferrari N, De Flora, Albini A. Angiopreven-tion: Angiogenesis is a common and key target for cancer chemopreventive agents. FASEB J 2002; 16 (1): 2-14.
  • Xie Y, Zhao QY, Li HY, Zhou X, Liu Y, Zhang H. Cur-cumin ameliorates cognitive deficits heavy ion irradiation-induced learning and memory deficits through enhancing of Nrf2 antioxidant signaling pathways. Pharmacol Biochem Behav 2014; 126: 181-6.
  • Zafarullah M, Li WQ, Sylvester J, Ahmad M. Molecu-lar mechanisms of Nacetylcysteine actions. Cell Mol Life Sci 2003; 60: 6-20.

The Effect of N-Acetylcysteine on Oxidant/Antioxidant Status in Irradiated Rats

Year 2020, Volume: 17 Issue: 3, 221 - 226, 01.12.2020
https://doi.org/10.32707/ercivet.828349

Abstract

N-Acetylcysteine (NAC) is both a strong antioxidant and a glutathione precursor. The effect of NAC on the oxidant/antioxidant status of some tissues of the irradiated rats was investigated. Twenty one rats were assigned to 3 groups; the control group, the irradiation group, for which physiological saline solution was administered as i.p. for three days and then, 9 Gy gamma irradiation was applied, and 3rd irradiation + NAC group for which NAC was adminis-tered as i.p. for three days as 300 mg/kg body weight and then the same dose of irradiation was applied. Upon irradia-tion, the increase determined in malondialdehyde (MDA) was significant in the liver, kidney, and brain tissues of the rats (P˂0.05). While glutathione peroxidase (GSH-Px) activity decreased in all of the tissues and superoxide dismutase (SOD) activity only in the liver (P˂0.01), glutathione (GSH) levels significantly increased in the kidney and ovarium tissues (P˂0.001). While NAC administration returned the increased MDA levels in the kidney and brain as a result of irradiation to normal levels (P˂0.05), it was determined that it did not return the increased MDA levels in the liver tissue to the normal level (P˂0.001). While NAC addition led to a significant increase in GSH levels of the liver, heart, spleen, brain and ovarium tissues compared to both control and irradiation groups, it caused a significant decrease in the kid-ney tissue compared to irradiation group (P˂0.001). As a result of NAC addition, a significant decrease was determined in spleen GSH-Px activity, heart and ovarium SOD activity compared to control and irradiation groups (P˂0.05). It can be asserted that GSH increasing by the addition of NAC is the main antioxidant that has a role in decreasing oxidative stress occurring as a result of irradiation. In the examination of MDA values, it was found that the addition of NAC pro-tected the kidney and brain against the oxidative damage induced by irradiation but NAC addition could remain insuffi-cient for the liver.

References

  • Aruoma OI, Halliwell B, Hoey BM, Butler J. The anti-oxidant action of N-acetylcysteine: its reaction with hydrogen peroxide, hydroxyl radical, super-oxide, and hypochlorous acid. Free Radic Biol Med 1989; 6: 593-7.
  • Ashry OM, Hussein EM, Abd El-Azime AS. Restora-tive role of persimmon leaf (Diospyros kaki) to gamma irradiation-induced oxidative stress and tissue injury in rats. Int J Radiat Biol 2017; 93(3): 324-9.
  • Benkovica V, Knezevica AH, Dikic D, Lisicic D, Orsolic N, Basic I, Kosalec I, Kopjar N. Radiopro-tective effects of propolis and quercetin in gamma-irradiated mice evaluated by the alkaline comet assay. Phytomedicine 2008; 15: 851-8.
  • Burgunder JM, Varriale A, Lauterburg BH. Effect of N-acetylcysteine on plasma cysteine and glutathi-one following paracetamol administration. Eur J Clin Pharmacol 1989; 36:127-31.
  • Comporti M. Lipid peroxidation and cellular damage in toxic liver injury. Lab Invest 1985; 53: 599-623.
  • Cosar R, Yurut-Caloglu V, Eskiocak S, Ozen A, Al-taner S, Ibis K, Turan N, Denizli B, Uzal C, Saynak M, Parlar S, Caloglu M, Uregen B, Kocak Z. Radiation-induced chronic oxidative renal dam-age can be reduced by amifostine. Med Oncol 2012; 29 (2):768-75.
  • De Ferreyra E, Villarruel M, Fernandez G, De Fenos O, Bernacchi A, De Castro C, Castro J. Further studies on the mechanism of the late protective effects of phenylmethylsulfonyl fluoride on carbon tetrachloride-induced liver necrosis. Exp Mol Pathol 1989; 5: 253-69.
  • Demir EO, Cakmak GK, Bakkal H, Turkcu UO, Kan-demir N, Demir AS, Tascılar O. N-acetyl-cysteine improves anastomotic wound healing after radio-therapy in rats. J Invest Surg 2011; 24 (4): 151-8.
  • Demirkol O, Adams C, Ercal N. Biologically important thiols in various vegetables and fruits. J Agric Food Chem 2004; 52 (26): 8151-4.
  • Duthie SJ, Ma A, Ross MA, Collins AR. Antioxidant supplementation decreases oxidative DNA dama-ge in human lymphocytes. Cancer Res 1996; 56 (6): 1291-5.
  • Ekici K, Temelli O, Parlakpinar H, Samdanci E, Polat A, Beytur A, Tanbek K, Ekici C, Dursun IH. Bene-ficial effects of aminoguanidine on radiotherapy-induced kidney and testis injury. Andrologia 2016; 48 (6): 683-92.
  • El-Gazzar MG, Zaher NH, El-Hossary EM, Ismail AFM. Radio-protective effect of some new curcu-min analogues. J Photochem Photobiol B 2016; 162: 694-702.
  • Gulbahar O, Aricioglu A, Akmansu M, Turkozer Z. Effects of radiation on protein oxidation and lipid peroxidation in the brain tissue. Transplant Proc 2009; 41 (10): 4394-6.
  • Hsu CC, Huang CN, Hung YC, Yin MC. Five cysteine containing compounds have antioxidative activity in Balb/cA mice. J Nutr 2004; 134: 149-52.
  • Karami M, Asri-Rezaei S, Dormanesh B, Nazariza-deh A. Comparative study of radioprotective ef-fects of selenium nanoparticles and sodium sele-nite in irradiation-induced nephropathy of mice model. Int J Radiat Biol 2018; 94 (1): 17-27.
  • Khattab HAH, Abdallah IZA, Yousef FM, Huwait EA. Efficiency of borage seeds oil against gamma irradiation-induced hepatotoxicity in male rats: possible antioxidant activity. Afr J Tradit Comple-ment Altern Med 2017; 14(4): 169-79.
  • Kilciksiz S, Demirel C, Erdal N, Gürgül S, Tamer L, Ayaz L, Ors Y. The effect of N-acetylcysteine on biomarkers for radiation-induced oxidative dam-age in a rat model. Acta Med Okayama 2008; 62(6): 403-9.
  • Lawenda BD, Kelly KM, Ladas EJ, et al. Should sup-plemental antioxidant administration be avoided during chemotherapy and radiation therapy? J Natl Cancer 2008; 100 (11): 773-83.
  • Lawrence RA, Burk RF. Glutathione peroxidase ac-tivity in selenium-deficient rat liver. Biochem Bio-phys Res Commun 1976; 71 (4): 952-8.
  • Liu Y, Zhang H, Zhang L, Zhou Q, Wang X, Long., Dong T, Zhao W. Antioxidant N-acetylcysteine attenuates the acute liver injury caused by X-ray in mice. Eur J Pharmacol 2007; 575 (1-3): 142-8.
  • Lowry OH, Rosebrough NJ, Farr AL, Randall RJ. Protein measurement with folin phenol reagent. J Biol Chem 1951; 193 (1): 265-75.
  • Mansour HH, Hafez HF, Fahmy NM, Hanafi N. Pro-tective effect of N-acetylcysteine against radiation induced DNA damage and hepatic toxicity in rats. Biochem Pharmacol 2008; 75 (3): 773-80.
  • Neal R, Matthews RH, Lutz P, Ercal N. Antioxidant role of N-acetyl cysteine isomers following high dose irradiation. Free Radic Biol Med 2003, 34 (6): 689-95.
  • Patton S, Kurtz GW. 2-Thiobarbituric acid as a rea-gent for detecting milk fat oxidation. J Dairy Sci 1951; 34: 669-74.
  • Placer ZA, Cushman LL, Johnson BC. Estimation of product of lipid peroxidation (malonyldialdehyde) in biochemical systems. Anal Biochem 1966; 16 (2): 359-64.
  • Radwan RR, Mohamed HA. Nigella sativa oil modula-tes the therapeutic efficacy of mesenchymal stem cells against liver injury in irradiated rats. J Pho-tochem Photobiol B 2018; 178: 447-56.
  • Scibior D, Skrzycki M, Podsiad M, Czeczot H. Gluta-thione level and glutathione-dependent enzyme activities in blood serum of patients with gastroin-testinal tract tumors. Clin Biochem 2008; 41: 852-8.
  • 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.
  • Sies H. Strategies of antioxidant defense. Eur J Bio-chem 1993; 215 (2): 213-9.
  • Simsek Y, Gurocak S, Turkoz Y, Akpolat N, Celik O, Ozer A, Yılmaz E, Turhan U, Ozyalin F. Ameliora-tive effects of resveratrol on acute ovarian toxicity induced by total body irradiation in young adult rats. J Pediatr Adolesc Gynecol 2012; 25 (4): 262-6.
  • Sun Y, Oberley WL, Li Y. A simple method for clinical assay of superoxide dismutase. Clin Chem 1988; 34: 497-500.
  • Thomas SH. Paracetamol (acetaminophen) poison-ing. Pharmacol Ther 1993; 60 (1): 91-120.
  • Tosetti F, Ferrari N, De Flora, Albini A. Angiopreven-tion: Angiogenesis is a common and key target for cancer chemopreventive agents. FASEB J 2002; 16 (1): 2-14.
  • Xie Y, Zhao QY, Li HY, Zhou X, Liu Y, Zhang H. Cur-cumin ameliorates cognitive deficits heavy ion irradiation-induced learning and memory deficits through enhancing of Nrf2 antioxidant signaling pathways. Pharmacol Biochem Behav 2014; 126: 181-6.
  • Zafarullah M, Li WQ, Sylvester J, Ahmad M. Molecu-lar mechanisms of Nacetylcysteine actions. Cell Mol Life Sci 2003; 60: 6-20.
There are 35 citations in total.

Details

Primary Language English
Journal Section Articles
Authors

Mehtap Ozcelık This is me 0000-0003-2362-4935

Mine Erısır This is me

Osman Guler This is me

Murat Baykara

Publication Date December 1, 2020
Submission Date April 13, 2020
Acceptance Date July 27, 2020
Published in Issue Year 2020 Volume: 17 Issue: 3

Cite

APA Ozcelık, M., Erısır, M., Guler, O., Baykara, M. (2020). The Effect of N-Acetylcysteine on Oxidant/Antioxidant Status in Irradiated Rats. Erciyes Üniversitesi Veteriner Fakültesi Dergisi, 17(3), 221-226. https://doi.org/10.32707/ercivet.828349
AMA Ozcelık M, Erısır M, Guler O, Baykara M. The Effect of N-Acetylcysteine on Oxidant/Antioxidant Status in Irradiated Rats. Erciyes Üniv Vet Fak Derg. December 2020;17(3):221-226. doi:10.32707/ercivet.828349
Chicago Ozcelık, Mehtap, Mine Erısır, Osman Guler, and Murat Baykara. “The Effect of N-Acetylcysteine on Oxidant/Antioxidant Status in Irradiated Rats”. Erciyes Üniversitesi Veteriner Fakültesi Dergisi 17, no. 3 (December 2020): 221-26. https://doi.org/10.32707/ercivet.828349.
EndNote Ozcelık M, Erısır M, Guler O, Baykara M (December 1, 2020) The Effect of N-Acetylcysteine on Oxidant/Antioxidant Status in Irradiated Rats. Erciyes Üniversitesi Veteriner Fakültesi Dergisi 17 3 221–226.
IEEE M. Ozcelık, M. Erısır, O. Guler, and M. Baykara, “The Effect of N-Acetylcysteine on Oxidant/Antioxidant Status in Irradiated Rats”, Erciyes Üniv Vet Fak Derg, vol. 17, no. 3, pp. 221–226, 2020, doi: 10.32707/ercivet.828349.
ISNAD Ozcelık, Mehtap et al. “The Effect of N-Acetylcysteine on Oxidant/Antioxidant Status in Irradiated Rats”. Erciyes Üniversitesi Veteriner Fakültesi Dergisi 17/3 (December 2020), 221-226. https://doi.org/10.32707/ercivet.828349.
JAMA Ozcelık M, Erısır M, Guler O, Baykara M. The Effect of N-Acetylcysteine on Oxidant/Antioxidant Status in Irradiated Rats. Erciyes Üniv Vet Fak Derg. 2020;17:221–226.
MLA Ozcelık, Mehtap et al. “The Effect of N-Acetylcysteine on Oxidant/Antioxidant Status in Irradiated Rats”. Erciyes Üniversitesi Veteriner Fakültesi Dergisi, vol. 17, no. 3, 2020, pp. 221-6, doi:10.32707/ercivet.828349.
Vancouver Ozcelık M, Erısır M, Guler O, Baykara M. The Effect of N-Acetylcysteine on Oxidant/Antioxidant Status in Irradiated Rats. Erciyes Üniv Vet Fak Derg. 2020;17(3):221-6.