Does Chitosan Introduce Protection Against Methotrexate-Induced Hepatorenal Injury in Rats?

Yıl 2024, Cilt: 14 Sayı: 1, 39 - 44, 28.03.2024

Ahmet Özer Şehirli Serkan Sayıner Kani Bilginaylar Hanife Özkayalar Aslı Aykaç

https://doi.org/10.33808/clinexphealthsci.1134320

Öz

Objective: Chitosan possesses antioxidant properties and exhibits anti-inflammatory characteristics. The objective of the investigation was to assess the effectiveness of chitosan in protecting against hepatorenal injury induced by methotrexate (MTX), a medication utilized for immunosuppression and chemotherapy.
Methods: Wistar albino rats were allocated into 3 different groups, each consisting of six animals (n=6). The control group received saline for 5 days (i.p.), the MTX group was administrated a single dose MTX (60 mg/kg, i.p.) along with saline for four days (i.p.), while MTX+Chitosan group received a single dose of MTX (60 mg/kg, i.p.) followed by Chitosan administration (200 mg/kg, i.p.) for four days. On the sixth day, the animals were decapitated, and blood and tissue samples were collected. BUN, creatinine and tissue inhibitors of metalloproteinase-1 (TIMP-1) levels and activities of AST, ALT, ALP, LDH, matrix metalloproteinases (MMP-3, MMP-8, MMP-9) activities were quantified in the blood. The liver and kidney were evaluated for caspase-3 and-9 through western blotting, while structural damage was examined using light microscopy.
Results: In the MTX administered group, blood and tissues values except for all TIMP-1 statistically increased when compared to the control group, while activity of TIMP-1 decreased significantly. The Chitosan-treated MTX group had comparable values to the control group.
Conclusion: Based on its influence on metalloproteinases and caspases, our findings lead to the conclusion that Chitosan offers a protective effect against liver and kidney damage induced by MTX.

Anahtar Kelimeler

Caspase, Chitosan, Methotrexate, MMP, TIMP-1

Proje Numarası

Yok

Kaynakça

• Jolivet J, Cowan KH, Curt GA, Clendeninn NJ, Chabner BA. The pharmacology and clinical use of methotrexate. New England Journal of Medicine 1983; 309(18):1094–1104. DOI: 10.1056/NEJM198311033091805.
• Braun J, Rau R. An update on methotrexate. Curr Opin Rheumatol 2009; 21(3):216–223. DOI: 10.1097/BOR.0b013e328329c79d.
• Dar A, Fehaid A, Alkhatani S, Alarifi S, Alqahtani W, Albasher G, Almeer R, Alfarraj S, Moneim AA. The protective role of luteolin against the methotrexate-induced hepato-renal toxicity via its antioxidative, anti-inflammatory, and anti-apoptotic effects in rats. Hum Exp Toxicol 2021; 40(7):1194–1207. DOI: 10.1177/0960327121991905.
• Al Maruf A, O’Brien PJ, Naserzadeh P, Fathian R, Salimi A, Pourahmad J. Methotrexate induced mitochondrial injury and cytochrome c release in rat liver hepatocytes. Drug Chem Toxicol 2018; 41(1):51–61. DOI: 10.1080/01480545.2017.1289221.
• Azouz AA, Saleh E, Abo-Saif AA. Aliskiren, tadalafil, and cinnamaldehyde alleviate joint destruction biomarkers; MMP-3 and RANKL; in complete Freund’s adjuvant arthritis model: Downregulation of IL-6/JAK2/STAT3 signaling pathway. Saudi Pharmaceutical Journal 2020; 28(9):1101–1111. DOI: 10.1016/j.jsps.2020.07.011.
• Ceylanlı D, Şehirli AÖ, Gençosman S, Teralı K, Şah H, Gülmez N, Sayıner S. Protective effects of alpha-lipoic acid against 5-fluorouracil-induced gastrointestinal mucositis in rats. Antioxidants 2022; 11(10):1930. DOI: 10.3390/antiox11101930.
• Gençosman S, Ceylanlı D, Şehirli AÖ, Teralı K, Bölükbaşı F, Çetinel Ş, Sayıner S. Investigation of the possible protective effect of n-acetylcysteine (nac) against irinotecan (cpt-11)-induced toxicity in rats. Antioxidants 2022; 11(11):2219. DOI: 10.3390/antiox11112219.
• Chauhan P, Sharma H, Kumar U, Mayachari A, Sangli G, Singh S. Protective effects of Glycyrrhiza glabra supplementation against methotrexate-induced hepato-renal damage in rats: An experimental approach. J Ethnopharmacol 2020; 263113209. DOI: 10.1016/j.jep.2020.113209.
• Bilginaylar K, Aykac A, Sayiner S, Özkayalar H, Şehirli AÖ. Evaluation of the antiapoptotic and anti-inflammatory properties of chitosan in methotrexate-induced oral mucositis in rats. Mol Biol Rep 2022; 49(4):3237–3245. DOI: 10.1007/s11033-022-07158-x.
• Çakır T, Özkan E, Dulundu E, Topaloğlu Ü, Şehirli AÖ, Ercan F, Şener E, Şener G. Caffeic acid phenethyl ester (CAPE) prevents methotrexate-induced hepatorenal oxidative injury in rats. Journal of Pharmacy and Pharmacology 2011; 63(12):1566–1571. DOI: 10.1111/j.2042-7158.2011.01359.x.
• Aslaner A, Çakır T, Çelik B, Doğan U, Mayir B, Akyüz C, Polat C, Baştürk A, Soyer V, Koç S, Şehirli AÖ. Does intraperitoneal medical ozone preconditioning and treatment ameliorate the methotrexate induced nephrotoxicity in rats? Int J Clin Exp Med 2015; 8(8):13811–7.
• Çakır T, Baştürk A, Polat C, Aslaner A, Durgut H, Şehirli AÖ, Gül M, Öğünç AV, Gül S, Sabuncuoglu MZ, Oruç MT. Does alfa lipoic acid prevent liver from methotrexate induced oxidative injury in rats? Acta Cir Bras 2015; 30(4):247–252. DOI: 10.1590/S0102-865020150040000003.
• Pradines B, Lievin-Le Moal V, Vauthier C, Ponchel G, Loiseau PM, Bouchemal K. Cell line-dependent cytotoxicity of poly(isobutylcyanoacrylate) nanoparticles coated with chitosan and thiolated chitosan: Insights from cultured human epithelial HeLa, Caco2/TC7 and HT-29/MTX cells. Int J Pharm 2015; 491(1–2):17–20. DOI: 10.1016/j.ijpharm.2015.06.001.
• Arpag H, Gül M, Aydemir Y, Atilla N, Yiğitcan B, Cakir T, Polat C, Þehirli Ö, Sayan M. Protective Effects of Alpha-Lipoic Acid on Methotrexate-Induced Oxidative Lung Injury in Rats. J Invest Surg 2018; 31(2):107–113. DOI: 10.1080/08941939.2017.1296513.
• Kısadere İ, Karaman M, Aydın MF, Donmez N, Usta M. The protective effects of chitosan oligosaccharide (COS) on cadmium-induced neurotoxicity in Wistar rats. Arch Environ Occup Health 2021; 1–9. DOI: 10.1080/19338244.2021.2008852.
• Ito M, Ban A, Ishihara M. Anti-ulcer effects of chitin and chitosan, healthy foods, in rats. Jpn J Pharmacol 2000; 82(3):218–225. DOI: 10.1254/jjp.82.218.
• Sathiyaseelan A, Saravanakumar K, Mariadoss AVA, Wang MH. PH-controlled nucleolin targeted release of dual drug from chitosan-gold based aptamer functionalized nano drug delivery system for improved glioblastoma treatment. Carbohydr Polym; 262. DOI: 10.1016/J.CARBPOL.2021.117907. Epub ahead of print 15 June 2021. DOI: 10.1016/J.CARBPOL.2021.117907.
• Mariadoss AVA, Vinayagam R, Senthilkumar V, Paulpandi M, Murugan K, Xu B, Gothandam KM, Kotakadi VS, David E. Phloretin loaded chitosan nanoparticles augments the pH-dependent mitochondrial-mediated intrinsic apoptosis in human oral cancer cells. Int J Biol Macromol 2019; 130997–1008. DOI: 10.1016/J.IJBIOMAC.2019.03.031.
• Wei X, Yang D, Xing Z, Zhao C, Wang L, Fan Y, Nie H, Liu H. Quercetin loaded liposomes modified with galactosylated chitosan prevent LPS/D-GalN induced acute liver injury. Materials Science and Engineering C 2021; 131112527. DOI: 10.1016/j.msec.2021.112527.
• Lu S, Kong S, Wang Y, Hu Z, Zhang L, Liao M. Gastric acid-response chitosan/alginate/tilapia collagen peptide composite hydrogel: Protection effects on alcohol-induced gastric mucosal injury. Carbohydr Polym 2022; 277118816. DOI: 10.1016/j.carbpol.2021.118816.
• Shalkami A-GS, Hassanein EHM, Sayed AM, Mohamed WR, Khalaf MM, Hemeida RAM. Hepatoprotective effects of phytochemicals berberine and umbelliferone against methotrexate-induced hepatic intoxication: Experimental studies and in silico evidence. Environmental Science and Pollution Research 2021; 28(47):67593–67607. DOI: 10.1007/s11356-021-15358-4.
• Nimbal SK, Gadad PC, Koti BC. Effect of ethanolic extract of Rosa centifolia against doxorubicin induced nephrotoxicity in albino rats. J Ayurveda Integr Med 2021; 12(4):657–662. DOI: 10.1016/j.jaim.2021.07.020.
• Liu S-H, Chen F-W, Chiang M-T. Chitosan oligosaccharide alleviates abnormal glucose metabolism without inhibition of hepatic lipid accumulation in a high-fat diet/streptozotocin-induced diabetic rat model. Mar Drugs 2021; 19(7):360. DOI: 10.3390/md19070360.
• Vannozzi L, Catalano E, Telkhozhayeva M, Teblum E, Yarmolenko A, Avraham ES, Konar R, Nessim GD, Ricotti L. Graphene oxide and reduced graphene oxide nanoflakes coated with glycol chitosan, propylene glycol alginate, and polydopamine: characterization and cytotoxicity in human chondrocytes. Nanomaterials 2021; 11(8):2105. DOI: 10.3390/nano11082105.
• Aksoy U, Savtekin G, Şehirli A, Kermeoğlu F, Kalender A, Özkayalar H, Sayıner S, Orhan K. Effects of alpha-lipoic acid therapy on experimentally induced apical periodontitis: A biochemical, histopathological and micro-CT analysis. Int Endod J 2019; 52(9):1317–1326. DOI: 10.1111/iej.13121.
• Soliman MM, Nassan MA, Ismail TA. Immunohistochemical and molecular study on the protective effect of curcumin against hepatic toxicity induced by paracetamol in wistar rats. BMC Complement Altern Med 2014; 14(1):457. DOI: 10.1186/1472-6882-14-457.
• Kollaras V, Valsami G, Lambropoulou M, Konstandi O, Kostomistsopoulos N, Pikoulis E, Simopoulos C, Tsaroucha A. Effect of silibinin on the expression of MMP2, MMP3, MMP9 and TIMP2 in kidney and lung after hepatic ischemia/reperfusion injury in an experimental rat model. Acta Cir Bras; 36(9): DOI: 10.1590/acb360904.
• Liu T, Wu X, Chen S, Wu P, Han H, Zhang H, Li J, Li G, Zhang S. A cationic polymeric prodrug with chemotherapeutic self-sensibilization co-delivering MMP-9 shRNA plasmid for a combined therapy to nasopharyngeal carcinoma. Drug Deliv 2019; 26(1):1280–1291. DOI: 10.1080/10717544.2019.1698674.
• Cardoso LM, Pansani TN, Hebling J, de Souza Costa CA, Basso FG. Chemotherapy drugs and inflammatory cytokines enhance matrix metalloproteinases expression by oral mucosa cells. Arch Oral Biol 2021; 127105159. DOI: 10.1016/j.archoralbio.2021.105159.
• Deyab G, Reine TM, Vuong TT, Jenssen T, Hjeltnes G, Agewall S, Mikkelsen K, Førre Ø, Fagerland MW, Kolset SO, Hollan I. Antirheumatic treatment is associated with reduced serum Syndecan-1 in Rheumatoid Arthritis. PLoS One 2021; 16(7):e0253247. DOI: 10.1371/journal.pone.0253247.
• Mattaveewong T, Wongkrasant P, Chanchai S, Pichyangkura R, Chatsudthipong V, Muanprasat C. Chitosan oligosaccharide suppresses tumor progression in a mouse model of colitis-associated colorectal cancer through AMPK activation and suppression of NF-κB and mTOR signaling. Carbohydr Polym 2016; 14530–36. DOI: 10.1016/j.carbpol.2016.02.077.
• Siahmansouri H, Somi MH, Babaloo Z, Baradaran B, Jadidi-Niaragh F, Atyabi F, Mohammadi H, Ahmadi M, Yousefi M. Effects of HMGA2 siRNA and doxorubicin dual delivery by chitosan nanoparticles on cytotoxicity and gene expression of HT-29 colorectal cancer cell line. Journal of Pharmacy and Pharmacology 2016; 68(9):1119–1130. DOI: 10.1111/jphp.12593.
• Chung DC, Long Le T, Ho NQC, Nguyen TT, Do DG, Do DT, Nguyen TPM, Nguyen TPT, Hoang NS. Evaluation of in vitro cytotoxicity and in vivo potential toxicity of the extract from in vitro cultivated Anoectochilus roxburghii Lindl. J Toxicol Environ Health A 2021; 84(24):987–1003. DOI: 10.1080/15287394.2021.1963363.
• Doan CC, Le TL, Ho NQC, La THL, Nguyen VC, Le VD, Nguyen TPT, Hoang NS. Bioactive chemical constituents, in vitro anti-proliferative activity and in vivo toxicity of the extract of Curcuma singularis Gagnep rhizomes. J Ethnopharmacol 2022; 284114803. DOI: 10.1016/j.jep.2021.114803.
• Zhang Y, Ahmad KA, Khan FU, Yan S, Ihsan AU, Ding Q. Chitosan oligosaccharides prevent doxorubicin-induced oxidative stress and cardiac apoptosis through activating p38 and JNK MAPK mediated Nrf2/ARE pathway. Chem Biol Interact 2019; 30554–65. DOI: 10.1016/J.CBI.2019.03.027.
• Zhang C, Yu L, Zhou Y, Zhao Q, Liu SQ. Chitosan oligosaccharides inhibit IL-1β-induced chondrocyte apoptosis via the P38 MAPK signaling pathway. Glycoconj J 2016; 33(5):735–744. DOI: 10.1007/S10719-016-9667-1.
• Çakir T, Polat C, Baştürk A, Gül M, Aslaner A, Durgut H, Şehirli A, Aykaç A, Bahar L, Sabuncuoglu MZ. The effect of alpha lipoic acid on rat kidneys in methotrexate induced oxidative injury. Eur Rev Med Pharmacol Sci 2015; 19(11):2132–2139.
• Çakır T, Baştürk A, Polat C, Aslaner A, Durgut H, Şehirli AÖ, Gül M, Öğünç AV, Gül S, Sabuncuoglu MZ, Oruç MT. Does alfa lipoic acid prevent liver from methotrexate induced oxidative injury in rats? Acta Cir Bras 2015; 30(4):247–252. DOI: 10.1590/S0102-865020150040000003.