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The evaluation of the protective effect of ambroxol against acetaminophen-induced hepatorenal toxicity in rats

Yıl 2024, Cilt: 28 Sayı: 4, 1210 - 1219, 28.06.2025

Serkan Sayıner , Sevgi Gençosman , Hüseyin Şah , Nurhayat Gülmez , Ahmet Özer Şehirli

Öz

Acetaminophen (APAP), widely used as an analgesic-antipyretic drug, can cause liver and kidney damage at high doses. This study explored the protective effects of a mucolytic agent and an antioxidant Ambroxol (AMB), against APAP-induced toxicity in rats. The experiment included four groups of Wistar albino rats each having 6 animals in both sexes: a control group, an AMB-only group (50 mg/kg orally), an APAP-only group (1000 mg/kg intraperitoneally), and a combination APAP+AMB group. Twenty-four hours following the administration of APAP administration, rats were sacrificed. Measurements of blood levels of liver enzymes (AST, ALT, ALP, LDH), kidney function markers (Urea, Creatinine), and antioxidant enzymes (SOD, GPx) were performed. GPx and SOD activities were also assessed in hepatic and renal tissue samples. Histological examination of hepatic and renal tissues was conducted using Haematoxylin and Eosin staining. Results showed that APAP significantly increased liver enzymes, BUN, and Creatinine levels, indicating hepatorenal damage. This was accompanied by a decrease in plasma GPx and SOD activities. However, AMB treatment significantly mitigated these changes. It improved enzyme activities and increased hepatic GPx. Histologically, the APAP group showed liver cell damage, necrosis, haemorrhage, and inflammation, which were notably reduced in the AMB-treated group. This study suggests that Ambroxol effectively counters APAP- induced hepatorenal damage by restoring antioxidant enzyme levels and normalizing functional enzyme activities, highlighting its potential as a protective agent.

Anahtar Kelimeler

Acetaminophen Ambroxol Glutathione peroxidase Superoxide dismutase Liver Kidney

Kaynakça

  • [1] Wang X, Wu Q, Liu A, Anadón A, Rodríguez JL, Martínez-Larrañaga MR, Yuan Z, Martínez MA. Paracetamol: overdose-induced oxidative stress toxicity, metabolism, and protective effects of various compounds in vivo and in vitro. Drug Metab Rev. 49 (4): 395-437. https://doi.org/10.1080/03602532.2017.1354014
  • [2] Tittarelli R, Pellegrini M, Scarpellini MG, Marinelli E, Bruti V, Luca NM Di, Busardò FP, Zaami S. Hepatotoxicity of paracetamol and related fatalities. Eur Rev Med Pharmacol Sci. 2017; 21 (1): 95–101.
  • [3] Abdeen A, Abdelkader A, Abdo M, Wareth G, Aboubakr M, Aleya L, Abdel-Daim M. Protective effect of cinnamon against acetaminophen-mediated cellular damage and apoptosis in renal tissue. Environ Sci Pollut Res. 2019; 26 (1): 240–249. https://doi.org/10.1007/s11356-018-3553-2
  • [4] Wang Z, Hu JN, Yan MH, Xing JJ, Liu WC, Li W. Caspase-mediated anti-apoptotic effect of ginsenoside Rg5, a main rare ginsenoside, on acetaminophen-ınduced hepatotoxicity in mice. J Agric Food Chem. 2017; 65 (42): 9226–9236. https://doi.org/10.1021/acs.jafc.7b03361
  • [5] Murad HAS, Habib H, Kamel Y, Alsayed S, Shakweer M, Elshal M. Thearubigins protect against acetaminophen-induced hepatic and renal injury in mice: Biochemical, histopathological, immunohistochemical, and flow cytometry study. Drug Chem Toxicol. 2016; 39 (2): 190–198. https://doi.org/10.3109/01480545.2015.1070170
  • [6] Uzkeser M, Karakus E, Albayrak A, Kiki İ, Bayir Y, Cadirci E, Unal D, Halici Z, Karadeniz A. Protective effect of Panax ginseng against N-acetyl-p-aminophenol-induced hepatotoxicity in rats. Afr J Pharm Pharmacol. 2012; 6 (36): 2634–2642. https://doi.org/10.5897/AJPP12.658
  • [7] Jothy SL, Aziz A, Chen Y, Sasidharan S. Antioxidant activity and hepatoprotective potential of Polyalthia longifolia and Cassia spectabilis leaves against paracetamol-induced liver injury. Evid Based Complement Alternat Med. 2012;2012:561284. https://doi.org/10.1155/2012/561284
  • [8] Ghosh J, Das J, Manna P, Sil PC. Acetaminophen induced renal injury via oxidative stress and TNF-α production: Therapeutic potential of arjunolic acid. Toxicology. 2010; 268 (1-2): 8–18. https://doi.org/10.1016/j.tox.2009.11.011
  • [9] Ozatik FY, Teksen Y, Kadioglu E, Ozatik O, Bayat Z. Effects of hydrogen sulfide on acetaminophen-induced acute renal toxicity in rats. Int Urol Nephrol. 2019; 51 (4): 745–754. https://doi.org/10.1007/s11255-018-2053-0
  • [10] Mugford CA, Tarloff JB. The contribution of oxidation and deacetylation to acetaminophen nephrotoxicity in female Sprague-Dawley rats. Toxicol Lett. 1997; 93 (1): 15–22. https://doi.org/10.1016/S0378-4274(97)00063-5
  • [11] Isik B, Bayrak R, Akcay A, Sogut S. Erdosteine against acetaminophen induced renal toxicity. Mol Cell Biochem. 2006; 287 (1–2): 185–191. https://doi.org/10.1007/s11010-005-9110-6
  • [12] Azarmehr N, Afshar P, Moradi M, Sadeghi H, Sadeghi H, Alipoor B, Khalvati B, Barmoudeh Z, Abbaszadeh-Goudarzi K, Doustimotlagh AH. Hepatoprotective and antioxidant activity of watercress extract on acetaminophen-induced hepatotoxicity in rats. Heliyon. 2019; 5 (7): e02072. https://doi.org/10.1016/j.heliyon.2019.e02072
  • [13] Cazan D, Klimek L, Sperl A, Plomer M, Kölsch S. Safety of ambroxol in the treatment of airway diseases in adult patients. Expert Opin Drug Saf. 2018; 17 (12): 1211–1224. https://doi.org/10.1080/14740338.2018.1533954
  • [14] Sunkari S, Thatikonda S, Pooladanda V, Challa VS, Godugu C. Protective effects of ambroxol in psoriasis like skin inflammation: Exploration of possible mechanisms. Int Immunopharmacol. 2019; 71 301–312. https://doi.org/10.1016/j.intimp.2019.03.035
  • [15] Gültekin Ç, Sayiner S, Çetinel Ş, Şehirli AÖ. Does Ambroxol alleviate kidney ischemia-reperfusion injury in rats? Iran J Basic Med Sci. 2022; 25 (8): 1037–1041. https://doi.org/10.22038/IJBMS.2022.64330.14148
  • [16] Gultekin C, Sehirli AO, Cetinel S, Sayiner S. Could Ambroxol reduce cytokines in hepatic ischemia-reperfusion injury in rats? Bratisl Lek Listy. 2022; 123 (5): 381–384. https://doi.org/10.4149/BLL_2022_060
  • [17] Nowak D, Antczak A, Król M, Bialasiewicz P, Pietras T. Antioxidant properties of ambroxol. Free Radic Biol Med. 1994; 16 (4): 517–522. https://doi.org/10.1016/0891-5849(94)90130-9
  • [18] Zhi QM, Yang LT, Sun HC. Protective effect of ambroxol against paraquat-induced pulmonary fibrosis in rats. Intern Med. 2011; 50 (18): 1879–1887. https://doi.org/10.2169/internalmedicine.50.5407
  • [19] Fersahoğlu MM, Özkan E, Velioğlu-Öğünç A, Sayıner S, Ercan F, Çilingir Kaya ÖT, Şehirli AÖ. Impact of pycnogenol on acetaminophen-ınduced hepatorenal damage. Biointerface Res Appl Chem. 2022; 12 (6): 8070–8080. https://doi.org/10.33263/BRIAC126.80708080
  • [20] Sener G, Omurtag GZ, Sehirli O, Tozan A, Yüksel M, Ercan F, Gedik N. Protective effects of Ginkgo biloba against acetaminophen-induced toxicity in mice. Mol Cell Biochem. 2006; 283 (1–2): 39–45. https://doi.org/10.1007/s11010-006-2268-8
  • [21] Sener G, Sehirli O, Cetinel S, Yeğen BG, Gedik N, Ayanoğlu-Dülger G. Protective effects of MESNA (2-mercaptoethane sulphonate) against acetaminophen-induced hepatorenal oxidative damage in mice. J Appl Toxicol. 2005; 25 (1): 20–29. https://doi.org/10.1002/jat.1012
  • [22] Li J, Gao Y, Cui L, He H, Zheng J, Mo S, Zhou X, Chu S, Sun X, Chen N, Wang H. Combination of monoammonium glycyrrhizinate and cysteine hydrochloride protects mice against acetaminophen-induced liver injury via Keap1/Nrf2/ARE pathway. J Pharm Pharmacol. 2022; 74 (5): 730–739. https://doi.org/10.1093/jpp/rgab180
  • [23] Wang K, Yang L, Zhou J, Pan X, He Z, Liu J, Zhang Y. Smilax china L. Polysaccharide Alleviates Oxidative Stress and Protects From Acetaminophen-Induced Hepatotoxicity via Activating the Nrf2-ARE Pathway. Front Pharmacol. 2022; 13 888560. https://doi.org/10.3389/fphar.2022.888560
  • [24] Dong K, Zhang M, Liu Y, Gao X, Wu X, Shi D, Guo C, Wang J. Pterostilbene-loaded soluplus/poloxamer 188 mixed micelles for protection against acetaminophen-ınduced acute liver ınjury. Mol Pharm. 2023; 20 (2): 1189–1201. https://doi.org/10.1021/acs.molpharmaceut.2c00881
  • [25] Hammad AM, Shawaqfeh B, Hikmat S, Al-Qirim T, Hamadneh L, Al-Kouz S, Awad MM, Hall FS. The role of vitamin e in protecting against oxidative stress, ınflammation, and the neurotoxic effects of acute paracetamol in pregnant female rats. Toxics. 2023; 11 (4): 368. https://doi.org/10.3390/toxics11040368
  • [26] Koç A, Gazi M, Caner Sayar A, Onk D, Ali Arı M, Süleyman B, Gökhan Ağgül A, Altındağ F, Altuner D, Süleyman H. Molecular mechanism of the protective effect of adenosine triphosphate against paracetamol-induced liver toxicity in rats. Gen Physiol Biophys. 2023; 42 (2): 201–208. https://doi.org/10.4149/gpb_2022055
  • [27] Gupta PR. Ambroxol hydrochloride in the management of idiopathic pulmonary fibrosis: Clinical trials are the need of the hour. Lung India. 2014; 31 (1): 43–46. https://doi.org/10.4103/0970-2113.125899
  • [28] Wang Y, Wang F-Y, Pan Z, Dai Y-Y, Xu H-J, Jin K-K, Wang W-T. Effects of ambroxol combined with low-dose heparin on TNF-alpha and IL-1beta in rabbits with acute lung injury. Chin J Appl Physiol. 2011; 27 (2): 231–235.
  • [29] Ebada ME. Essential oils of green cumin and chamomile partially protect against acute acetaminophen hepatotoxicity in rats. An Acad Bras Cienc. 2018; 90 (2 suppl 1): 2347–2358. https://doi.org/10.1590/0001-3765201820170825
  • [30] Ko J-W, Shin J-Y, Kim J-W, Park S-H, Shin N-R, Lee I-C, Shin I-S, Moon C, Kim S-H, Kim S-H, Kim J-C. Protective effects of diallyl disulfide against acetaminophen-induced nephrotoxicity: A possible role of CYP2E1 and NF-κB. Food Chem Toxicol. 2017; 102 156–165. https://doi.org/10.1016/j.fct.2017.02.021
  • [31] Reshi MS, Shrivastava S, Jaswal A, Sinha N, Uthra C, Shukla S. Gold nanoparticles ameliorate acetaminophen induced hepato-renal injury in rats. Exp Toxicol Pathol. 2017; 69 (4): 231–240. https://doi.org/10.1016/j.etp.2017.01.009
  • [32] Jiang K, Wang X, Mao X, Lao H, Zhang J, Wang G, Cao Y, Tong I, Zhang F. Ambroxol alleviates hepatic ıschemia reperfusion ınjury by antioxidant and antiapoptotic pathways. Transplant Proc. 2013; 45 (6): 2439–2445. https://doi.org/10.1016/j.transproceed.2013.04.007
  • [33] Elbe H, Gul M, Cetin A, Taslidere E, Ozyalin F, Turkoz Y, Otlu A. Resveratrol reduces light and electron microscopic changes in acetaminophen-induced hepatotoxicity in rats: Role of iNOS expression. Ultrastruct Pathol. 2018; 42(1): 39-48. https://doi.org/10.1080/01913123.2017.1374313
  • [34] Zhao SP, Guo QL, Wang RK, Wang E. Oxidative and anti-oxidative effects of ambroxol on acute hydrochloric acid-induced lung injury in rats. Zhong Nan Da Xue Xue Bao Yi Xue Ban. 2004; 29 (5): 586–588.
  • [35] Baluchamy S, Ravichandran P, Periyakaruppan A, Ramesh V, Hall JC, Zhang Y, Jejelowo O, Gridley DS, Wu H, Ramesh GT. Induction of cell death through alteration of oxidants and antioxidants in lung epithelial cells exposed to high energy protons. J Biol Chem. 2010; 285 (32): 24769–24774. https://doi.org/10.1074/jbc.M110.138099
  • [36] Ciftci O, Onat E, Cetin A. The beneficial effects of fish oil following cisplatin-ınduced oxidative and histological damage in liver of rats. Iran J Pharm Res. 2017; 16 (4): 1424–1431.
  • [37] Aykaç A, Şah H, Kükner A, Sayıner S, Şehirli AÖ. Effects of chitosan on cisplatin-ınduced hepatorenal toxicity in an animal model. Istanbul Med J. 2022; 23 (3): 183–188. https://doi.org/10.4274/imj.galenos.2022.54077
  • [38] Moneim LMA, Helmy MW, El-Abhar HS. Co-targeting of endothelin-A and vitamin D receptors: a novel strategy to ameliorate cisplatin-induced nephrotoxicity. Pharmacol Reports. 2019; 71 (5): 917–925. https://doi.org/10.1016/j.pharep.2019.04.018
  • [39] Şah H, Gülmez N, Söyler G, Sayıner S, Şehirli AÖ, Kükner A. Effect of kefir on ıncreased apoptosis in liver and kidney in cisplatin toxicity. Int J Morphol. 2022; 40 (2): 480–488.

Yıl 2024, Cilt: 28 Sayı: 4, 1210 - 1219, 28.06.2025

Serkan Sayıner , Sevgi Gençosman , Hüseyin Şah , Nurhayat Gülmez , Ahmet Özer Şehirli

Öz

Kaynakça

  • [1] Wang X, Wu Q, Liu A, Anadón A, Rodríguez JL, Martínez-Larrañaga MR, Yuan Z, Martínez MA. Paracetamol: overdose-induced oxidative stress toxicity, metabolism, and protective effects of various compounds in vivo and in vitro. Drug Metab Rev. 49 (4): 395-437. https://doi.org/10.1080/03602532.2017.1354014
  • [2] Tittarelli R, Pellegrini M, Scarpellini MG, Marinelli E, Bruti V, Luca NM Di, Busardò FP, Zaami S. Hepatotoxicity of paracetamol and related fatalities. Eur Rev Med Pharmacol Sci. 2017; 21 (1): 95–101.
  • [3] Abdeen A, Abdelkader A, Abdo M, Wareth G, Aboubakr M, Aleya L, Abdel-Daim M. Protective effect of cinnamon against acetaminophen-mediated cellular damage and apoptosis in renal tissue. Environ Sci Pollut Res. 2019; 26 (1): 240–249. https://doi.org/10.1007/s11356-018-3553-2
  • [4] Wang Z, Hu JN, Yan MH, Xing JJ, Liu WC, Li W. Caspase-mediated anti-apoptotic effect of ginsenoside Rg5, a main rare ginsenoside, on acetaminophen-ınduced hepatotoxicity in mice. J Agric Food Chem. 2017; 65 (42): 9226–9236. https://doi.org/10.1021/acs.jafc.7b03361
  • [5] Murad HAS, Habib H, Kamel Y, Alsayed S, Shakweer M, Elshal M. Thearubigins protect against acetaminophen-induced hepatic and renal injury in mice: Biochemical, histopathological, immunohistochemical, and flow cytometry study. Drug Chem Toxicol. 2016; 39 (2): 190–198. https://doi.org/10.3109/01480545.2015.1070170
  • [6] Uzkeser M, Karakus E, Albayrak A, Kiki İ, Bayir Y, Cadirci E, Unal D, Halici Z, Karadeniz A. Protective effect of Panax ginseng against N-acetyl-p-aminophenol-induced hepatotoxicity in rats. Afr J Pharm Pharmacol. 2012; 6 (36): 2634–2642. https://doi.org/10.5897/AJPP12.658
  • [7] Jothy SL, Aziz A, Chen Y, Sasidharan S. Antioxidant activity and hepatoprotective potential of Polyalthia longifolia and Cassia spectabilis leaves against paracetamol-induced liver injury. Evid Based Complement Alternat Med. 2012;2012:561284. https://doi.org/10.1155/2012/561284
  • [8] Ghosh J, Das J, Manna P, Sil PC. Acetaminophen induced renal injury via oxidative stress and TNF-α production: Therapeutic potential of arjunolic acid. Toxicology. 2010; 268 (1-2): 8–18. https://doi.org/10.1016/j.tox.2009.11.011
  • [9] Ozatik FY, Teksen Y, Kadioglu E, Ozatik O, Bayat Z. Effects of hydrogen sulfide on acetaminophen-induced acute renal toxicity in rats. Int Urol Nephrol. 2019; 51 (4): 745–754. https://doi.org/10.1007/s11255-018-2053-0
  • [10] Mugford CA, Tarloff JB. The contribution of oxidation and deacetylation to acetaminophen nephrotoxicity in female Sprague-Dawley rats. Toxicol Lett. 1997; 93 (1): 15–22. https://doi.org/10.1016/S0378-4274(97)00063-5
  • [11] Isik B, Bayrak R, Akcay A, Sogut S. Erdosteine against acetaminophen induced renal toxicity. Mol Cell Biochem. 2006; 287 (1–2): 185–191. https://doi.org/10.1007/s11010-005-9110-6
  • [12] Azarmehr N, Afshar P, Moradi M, Sadeghi H, Sadeghi H, Alipoor B, Khalvati B, Barmoudeh Z, Abbaszadeh-Goudarzi K, Doustimotlagh AH. Hepatoprotective and antioxidant activity of watercress extract on acetaminophen-induced hepatotoxicity in rats. Heliyon. 2019; 5 (7): e02072. https://doi.org/10.1016/j.heliyon.2019.e02072
  • [13] Cazan D, Klimek L, Sperl A, Plomer M, Kölsch S. Safety of ambroxol in the treatment of airway diseases in adult patients. Expert Opin Drug Saf. 2018; 17 (12): 1211–1224. https://doi.org/10.1080/14740338.2018.1533954
  • [14] Sunkari S, Thatikonda S, Pooladanda V, Challa VS, Godugu C. Protective effects of ambroxol in psoriasis like skin inflammation: Exploration of possible mechanisms. Int Immunopharmacol. 2019; 71 301–312. https://doi.org/10.1016/j.intimp.2019.03.035
  • [15] Gültekin Ç, Sayiner S, Çetinel Ş, Şehirli AÖ. Does Ambroxol alleviate kidney ischemia-reperfusion injury in rats? Iran J Basic Med Sci. 2022; 25 (8): 1037–1041. https://doi.org/10.22038/IJBMS.2022.64330.14148
  • [16] Gultekin C, Sehirli AO, Cetinel S, Sayiner S. Could Ambroxol reduce cytokines in hepatic ischemia-reperfusion injury in rats? Bratisl Lek Listy. 2022; 123 (5): 381–384. https://doi.org/10.4149/BLL_2022_060
  • [17] Nowak D, Antczak A, Król M, Bialasiewicz P, Pietras T. Antioxidant properties of ambroxol. Free Radic Biol Med. 1994; 16 (4): 517–522. https://doi.org/10.1016/0891-5849(94)90130-9
  • [18] Zhi QM, Yang LT, Sun HC. Protective effect of ambroxol against paraquat-induced pulmonary fibrosis in rats. Intern Med. 2011; 50 (18): 1879–1887. https://doi.org/10.2169/internalmedicine.50.5407
  • [19] Fersahoğlu MM, Özkan E, Velioğlu-Öğünç A, Sayıner S, Ercan F, Çilingir Kaya ÖT, Şehirli AÖ. Impact of pycnogenol on acetaminophen-ınduced hepatorenal damage. Biointerface Res Appl Chem. 2022; 12 (6): 8070–8080. https://doi.org/10.33263/BRIAC126.80708080
  • [20] Sener G, Omurtag GZ, Sehirli O, Tozan A, Yüksel M, Ercan F, Gedik N. Protective effects of Ginkgo biloba against acetaminophen-induced toxicity in mice. Mol Cell Biochem. 2006; 283 (1–2): 39–45. https://doi.org/10.1007/s11010-006-2268-8
  • [21] Sener G, Sehirli O, Cetinel S, Yeğen BG, Gedik N, Ayanoğlu-Dülger G. Protective effects of MESNA (2-mercaptoethane sulphonate) against acetaminophen-induced hepatorenal oxidative damage in mice. J Appl Toxicol. 2005; 25 (1): 20–29. https://doi.org/10.1002/jat.1012
  • [22] Li J, Gao Y, Cui L, He H, Zheng J, Mo S, Zhou X, Chu S, Sun X, Chen N, Wang H. Combination of monoammonium glycyrrhizinate and cysteine hydrochloride protects mice against acetaminophen-induced liver injury via Keap1/Nrf2/ARE pathway. J Pharm Pharmacol. 2022; 74 (5): 730–739. https://doi.org/10.1093/jpp/rgab180
  • [23] Wang K, Yang L, Zhou J, Pan X, He Z, Liu J, Zhang Y. Smilax china L. Polysaccharide Alleviates Oxidative Stress and Protects From Acetaminophen-Induced Hepatotoxicity via Activating the Nrf2-ARE Pathway. Front Pharmacol. 2022; 13 888560. https://doi.org/10.3389/fphar.2022.888560
  • [24] Dong K, Zhang M, Liu Y, Gao X, Wu X, Shi D, Guo C, Wang J. Pterostilbene-loaded soluplus/poloxamer 188 mixed micelles for protection against acetaminophen-ınduced acute liver ınjury. Mol Pharm. 2023; 20 (2): 1189–1201. https://doi.org/10.1021/acs.molpharmaceut.2c00881
  • [25] Hammad AM, Shawaqfeh B, Hikmat S, Al-Qirim T, Hamadneh L, Al-Kouz S, Awad MM, Hall FS. The role of vitamin e in protecting against oxidative stress, ınflammation, and the neurotoxic effects of acute paracetamol in pregnant female rats. Toxics. 2023; 11 (4): 368. https://doi.org/10.3390/toxics11040368
  • [26] Koç A, Gazi M, Caner Sayar A, Onk D, Ali Arı M, Süleyman B, Gökhan Ağgül A, Altındağ F, Altuner D, Süleyman H. Molecular mechanism of the protective effect of adenosine triphosphate against paracetamol-induced liver toxicity in rats. Gen Physiol Biophys. 2023; 42 (2): 201–208. https://doi.org/10.4149/gpb_2022055
  • [27] Gupta PR. Ambroxol hydrochloride in the management of idiopathic pulmonary fibrosis: Clinical trials are the need of the hour. Lung India. 2014; 31 (1): 43–46. https://doi.org/10.4103/0970-2113.125899
  • [28] Wang Y, Wang F-Y, Pan Z, Dai Y-Y, Xu H-J, Jin K-K, Wang W-T. Effects of ambroxol combined with low-dose heparin on TNF-alpha and IL-1beta in rabbits with acute lung injury. Chin J Appl Physiol. 2011; 27 (2): 231–235.
  • [29] Ebada ME. Essential oils of green cumin and chamomile partially protect against acute acetaminophen hepatotoxicity in rats. An Acad Bras Cienc. 2018; 90 (2 suppl 1): 2347–2358. https://doi.org/10.1590/0001-3765201820170825
  • [30] Ko J-W, Shin J-Y, Kim J-W, Park S-H, Shin N-R, Lee I-C, Shin I-S, Moon C, Kim S-H, Kim S-H, Kim J-C. Protective effects of diallyl disulfide against acetaminophen-induced nephrotoxicity: A possible role of CYP2E1 and NF-κB. Food Chem Toxicol. 2017; 102 156–165. https://doi.org/10.1016/j.fct.2017.02.021
  • [31] Reshi MS, Shrivastava S, Jaswal A, Sinha N, Uthra C, Shukla S. Gold nanoparticles ameliorate acetaminophen induced hepato-renal injury in rats. Exp Toxicol Pathol. 2017; 69 (4): 231–240. https://doi.org/10.1016/j.etp.2017.01.009
  • [32] Jiang K, Wang X, Mao X, Lao H, Zhang J, Wang G, Cao Y, Tong I, Zhang F. Ambroxol alleviates hepatic ıschemia reperfusion ınjury by antioxidant and antiapoptotic pathways. Transplant Proc. 2013; 45 (6): 2439–2445. https://doi.org/10.1016/j.transproceed.2013.04.007
  • [33] Elbe H, Gul M, Cetin A, Taslidere E, Ozyalin F, Turkoz Y, Otlu A. Resveratrol reduces light and electron microscopic changes in acetaminophen-induced hepatotoxicity in rats: Role of iNOS expression. Ultrastruct Pathol. 2018; 42(1): 39-48. https://doi.org/10.1080/01913123.2017.1374313
  • [34] Zhao SP, Guo QL, Wang RK, Wang E. Oxidative and anti-oxidative effects of ambroxol on acute hydrochloric acid-induced lung injury in rats. Zhong Nan Da Xue Xue Bao Yi Xue Ban. 2004; 29 (5): 586–588.
  • [35] Baluchamy S, Ravichandran P, Periyakaruppan A, Ramesh V, Hall JC, Zhang Y, Jejelowo O, Gridley DS, Wu H, Ramesh GT. Induction of cell death through alteration of oxidants and antioxidants in lung epithelial cells exposed to high energy protons. J Biol Chem. 2010; 285 (32): 24769–24774. https://doi.org/10.1074/jbc.M110.138099
  • [36] Ciftci O, Onat E, Cetin A. The beneficial effects of fish oil following cisplatin-ınduced oxidative and histological damage in liver of rats. Iran J Pharm Res. 2017; 16 (4): 1424–1431.
  • [37] Aykaç A, Şah H, Kükner A, Sayıner S, Şehirli AÖ. Effects of chitosan on cisplatin-ınduced hepatorenal toxicity in an animal model. Istanbul Med J. 2022; 23 (3): 183–188. https://doi.org/10.4274/imj.galenos.2022.54077
  • [38] Moneim LMA, Helmy MW, El-Abhar HS. Co-targeting of endothelin-A and vitamin D receptors: a novel strategy to ameliorate cisplatin-induced nephrotoxicity. Pharmacol Reports. 2019; 71 (5): 917–925. https://doi.org/10.1016/j.pharep.2019.04.018
  • [39] Şah H, Gülmez N, Söyler G, Sayıner S, Şehirli AÖ, Kükner A. Effect of kefir on ıncreased apoptosis in liver and kidney in cisplatin toxicity. Int J Morphol. 2022; 40 (2): 480–488.
Toplam 39 adet kaynakça vardır.

Ayrıntılar

Birincil Dil İngilizce
Konular Temel Farmakoloji
Bölüm Articles
Yazarlar

Serkan Sayıner 0000-0002-3297-5369

Sevgi Gençosman 0000-0003-1979-3058

Hüseyin Şah 0000-0003-0480-1609

Nurhayat Gülmez 0000-0003-1609-2598

Ahmet Özer Şehirli 0000-0002-5175-9290

Yayımlanma Tarihi 28 Haziran 2025
Gönderilme Tarihi 6 Şubat 2024
Kabul Tarihi 14 Mart 2024
Yayımlandığı Sayı Yıl 2024 Cilt: 28 Sayı: 4

Kaynak Göster

APA Sayıner, S., Gençosman, S., Şah, H., Gülmez, N., vd. (2025). The evaluation of the protective effect of ambroxol against acetaminophen-induced hepatorenal toxicity in rats. Journal of Research in Pharmacy, 28(4), 1210-1219.
AMA Sayıner S, Gençosman S, Şah H, Gülmez N, Şehirli AÖ. The evaluation of the protective effect of ambroxol against acetaminophen-induced hepatorenal toxicity in rats. J. Res. Pharm. Temmuz 2025;28(4):1210-1219.
Chicago Sayıner, Serkan, Sevgi Gençosman, Hüseyin Şah, Nurhayat Gülmez, ve Ahmet Özer Şehirli. “The Evaluation of the Protective Effect of Ambroxol Against Acetaminophen-Induced Hepatorenal Toxicity in Rats”. Journal of Research in Pharmacy 28, sy. 4 (Temmuz 2025): 1210-19.
EndNote Sayıner S, Gençosman S, Şah H, Gülmez N, Şehirli AÖ (01 Temmuz 2025) The evaluation of the protective effect of ambroxol against acetaminophen-induced hepatorenal toxicity in rats. Journal of Research in Pharmacy 28 4 1210–1219.
IEEE S. Sayıner, S. Gençosman, H. Şah, N. Gülmez, ve A. Ö. Şehirli, “The evaluation of the protective effect of ambroxol against acetaminophen-induced hepatorenal toxicity in rats”, J. Res. Pharm., c. 28, sy. 4, ss. 1210–1219, 2025.
ISNAD Sayıner, Serkan vd. “The Evaluation of the Protective Effect of Ambroxol Against Acetaminophen-Induced Hepatorenal Toxicity in Rats”. Journal of Research in Pharmacy 28/4 (Temmuz 2025), 1210-1219.
JAMA Sayıner S, Gençosman S, Şah H, Gülmez N, Şehirli AÖ. The evaluation of the protective effect of ambroxol against acetaminophen-induced hepatorenal toxicity in rats. J. Res. Pharm. 2025;28:1210–1219.
MLA Sayıner, Serkan vd. “The Evaluation of the Protective Effect of Ambroxol Against Acetaminophen-Induced Hepatorenal Toxicity in Rats”. Journal of Research in Pharmacy, c. 28, sy. 4, 2025, ss. 1210-9.
Vancouver Sayıner S, Gençosman S, Şah H, Gülmez N, Şehirli AÖ. The evaluation of the protective effect of ambroxol against acetaminophen-induced hepatorenal toxicity in rats. J. Res. Pharm. 2025;28(4):1210-9.