Protective Effect of Chromium Picolinate on Methotrexate Induced Nephrotoxicity in a Rat Model
DOI:
https://doi.org/10.31351/vol35iss2pp19-27Keywords:
antioxidants, Nephrotoxicity, Chromium picolinate, Methotrexate, Superoxide dismutase.Abstract
Methotrexate, a folic acid antagonist, is a chemotherapeutic agent frequently employed in treating certain forms of cancer. Nephrotoxicity caused by high-dose Methotrexate is a medical emergency due to the delayed renal excretion of Methotrexate. Chromium is a trace element found in certain foods and the environment. The primary function of chromium is to regulate glucose levels, which is used as a supplement by people with type 2 diabetes Mellitus. This study aimed to evaluate the renoprotective effect of chromium against Methotrexate-induced Nephrotoxicity in rats. Thirty-two Wistar rats were allocated into four groups and treated as Group-1 (Control group): The rat was administered distilled water orally as a vehicle for eight consecutive days. Group-2 (Induction group): Methotrexate was injected in rats at a single dose of 20 mg/kg intraperitoneally on the first day. On the following day, the rats received distilled water for seven days. Group-3 (Chromium 2mg): methotrexate injected Rats at a dose of 20 mg/kg intraperitoneally, as a single dose on the first day. On the following day, the rats received Chromium picolinate at a dose (2mg/kg) orally by oral gavage for seven days. Group-4 (Chromium 4mg): Methotrexate injected in rats at a dose of 20 mg/kg intraperitoneally, as a single dose on the first day. On the following day, the rats receive Chromium picolinate at a dose (4mg/kg) orally by oral gavage for seven days. The Results of our study indicated that injection (20mg/kg) of Methotrexate caused a significant increase in creatinine and blood urea nitrogen, malondialdehyde, and a significant reduction in superoxide dismutase-1. Interestingly, treatment with chromium picolinate (2mg/kg) and (4mg/kg) showed significant drops in creatinine and blood urea nitrogen and malondialdehyde and a significant elevation in superoxide dismutase-1 compared to Methotrexate-treated rats. In conclusion, the current investigation revealed that the administration of chromium to rats has a beneficial impact on reducing Nephrotoxicity generated by Methotrexate. This is achievd by enhancing antioxidant defenses of the kidneys.
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References
Rashed AR, Mohamed AS, Soliman AM. Ameliorative Effect of Galium Verum (Rubiaceae Family) Methanolic Extract on Folic Acid-induced Acute Kidney Injury in Male Rats. Iraqi J Pharm Sci. 2023; 32(3):14–24.
Ronco C, Bellomo R, Kellum JA. Acute kidney injury. Lancet. 2019; 394(10212):1949–1964.
Rewa O, Bagshaw SM. Acute kidney injury-epidemiology, outcomes and economics. Nat Rev Nephrol. 2014;10(4):193-207.
Sales GTM, Foresto RD. Drug-induced nephrotoxicity. Rev Assoc Med Bras (1992). 2020;66Suppl 1(Suppl 1):s82-s90.
Soares S, Souza LCR, Cronin MT, Waaga-Gasser AM , Grossi MF, Franco GR, Tagliati CA. Biomarkers and in vitro strategies for nephrotoxicity and renal disease assessment. J Nephrol Renal Dis. 2020; 5:1-14 ISSN 2399-908X.
Morsy MA, El-Sheikh AAK, Ibrahim ARN, El-Daly M. Protection of hesperidin against Methotrexate-Induced Nephrotoxicity may be Mediated by Nrf2/HO-1 Pathway. Indian J Pharm Educ Res. 2021; 55(4):1066–73
Ramsey LB, Balis FM, O'Brien MM, Schmiegelow K, Pauley JL, Bleyer A, Widemann BC, Askenazi D, Bergeron S, Shirali A, Schwartz S, Vinks AA, Heldrup J. Consensus Guideline for Use of Glucarpidase in Patients with High-Dose Methotrexate Induced Acute Kidney Injury and Delayed Methotrexate Clearance. Oncologist. 2018;23(1):52-61.
Mohammed Zakri NM, Al-Shawi NN. Possible protective effects of two different doses of Cyanocobalamin against Methotrexate Nephrotoxicity Model in Rats. Iraqi J Pharm Sci. 2022; 31(2):211–7.
Mahmoud AM , Hussein OE , Abd El-Twab SM , Hozayen WG . Ferulic acid protects against methotrexate nephrotoxicity via activation of Nrf2/ARE/HO-1 signaling and PPARγ, and suppression of NF-κB/NLRP3 inflammasome axis. Food Funct. 2019;10(8):4593-4607.
Abdel-Daim MM, Khalifa HA, Abushouk AI, Dkhil MA, Al-Quraishy SA. Diosmin Attenuates Methotrexate-Induced Hepatic, Renal, and Cardiac Injury: A Biochemical and Histopathological Study in Mice. Oxid Med Cell Longev. 2017; 2017:1–10.
Stępniowska A, Juśkiewicz J, Tutaj K, Fotschki J, Fotschki B, Ognik K. Effect of chromium picolinate and chromium nanoparticles added to low-or high-fat diets on chromium biodistribution and the blood level of selected minerals in rats. Pol J Food Nutr Sci. 2022; 72(3): 229-238.
Prasad S, Yadav KK, Kumar S, Gupta N, Cabral-Pinto MMS, Rezania S, Radwan N, Alam J. Chromium contamination and effect on environmental health and its remediation: A sustainable approaches. J Environ Manage. 2021;285:112174.
MARMETT B, NUNES RB. Effects of chromium picolinate supplementation on control of metabolic variables: A Systematic Review. J Food Nutr Res. 2016; 4(10): 633-639.
Kooshki F, Tutunchi H, Vajdi M, Karimi A, Niazkar HR, Shoorei H, Pourghassem Gargari B. A Comprehensive insight into the effect of chromium supplementation on oxidative stress indices in diabetes mellitus: A systematic review. Clin Exp Pharmacol Physiol. 2021 Mar;48(3):291-309.
Morsy MA, El-Sheikh AAK, Abdel-Hafez SMN, Kandeel M, Abdel-Gaber SA. Paeonol Protects Against Methotrexate-Induced Nephrotoxicity via Upregulation of P-gp Expression and Inhibition of TLR4/NF-κB Pathway. Front Pharmacol. 2022 Feb 4;13:774387.
Liu Y, Wang D. Administration of Chromium (III) and manganese (II) as a potential protective approach against Daunorubicin-Induced Cardiotoxicity: in vitro and in vivo Experimental Evidence. Biol. Trace Elem. Res. 2013; 156(1–3):253–61.
Aledani AHE, Khudhair NA, Alrafas HR. Effect of different methods of anesthesia on physiobiochemical parameters in laboratory male rats. Basra J Vet Res. 2020; 19(1): 206-214.
Greenfield EA. Sampling and Preparation of Mouse and Rat Serum. Cold Spring Harb Protoc. 2017S;2017(11):pdb.prot100271.
Voller A, Bartlett A, Bidwell DE. Enzyme immunoassays with special reference to ELISA techniques. J Clin Pathol. 1978;31(6):507-20.
Mahmood SH, Hassan AF. The Protective Effect of Omega-7 on Cisplatin-Induced Nephrotoxicity in Rat Model. Iraqi J Pharm Sci. 2023; 32(2):128–33.
Robinson N, Ganesan R, Hegedűs C, Kovács K, Kufer TA, Virág L. Programmed necrotic cell death of macrophages: Focus on pyroptosis, necroptosis, and parthanatos. Redox Biol. 2019;26:101239.
Mahmood YS, Kadhim SH. Protective Effects of Citronellol Against Rhabdomyolysis-Induced Acute Kidney Injury in Mice by Inhibiting NF-κB and IL-1β Signaling Pathway. Iraqi J Pharm Sci. 2023; 32:85–90.
ALDOSSARY SA. Protective effect of hesperidin against methotrexate-induced nephrotoxicity in rats. Life Science Journal. 2019; 16(2): 18-22.
Yeh HC, Ting IW, Huang HC, Chiang HY, Kuo CC.Acute kidney injury in the outpatient setting associates with risk of end-stage renal disease and death in patients with CKD. Sci Rep. 2019; 9(1): 17658.
Finlay S, Bray B, Lewington AJ, Hunter-Rowe CT, Banerjee A, Atkinson JM, Jones MC. Identification of risk factors associated with acute kidney injury in patients admitted to acute medical units. Clin Med (Lond). 2013;13(3):233-8.
Amitai I, Rozovski U, El-Saleh R, Shimony S, Shepshelovich D, Rozen-Zvi B, Raanani P, Gafter-Gvili A, Gurion R. Risk factors for high-dose methotrexate associated acute kidney injury in patients with hematological malignancies. Hematol Oncol. 2020;38(4):584-588.
Hamed KM, Dighriri IM, Baomar AF, Alharthy BT, Alenazi FE, Alali GH, Alenazy RH, Alhumaidi NT, Alhulayfi DH, Alotaibi YB, Alhumaidan SS, Alhaddad ZA, Humadi AA, Alzahrani SA, Alobaid RH. Overview of Methotrexate Toxicity: A Comprehensive Literature Review. Cureus. 2022;14(9):e29518.
Wasfey EF, Shaaban M, Essam M, Ayman Y, Kamar S, Mohasseb T, Rozik R, Khaled H, Eladly M, Elissawi M, Bassem A, Elshora SZ, Radwan SM. Infliximab Ameliorates Methotrexate-Induced Nephrotoxicity in Experimental Rat Model: Impact on Oxidative Stress, Mitochondrial Biogenesis, Apoptotic and Autophagic Machineries. Cell Biochem Biophys. 2023;81(4):717-726.
Mahmoud AM, Germoush MO, Al-Anazi KM, Mahmoud AH, Farah MA, Allam AA. Commiphora molmol protects against methotrexate-induced nephrotoxicity by up-regulating Nrf2/ARE/HO-1 signaling. Biomed Pharmacother. 2018;106:499-509.
Yano M, Nishino M, Ukita K, Kawamura A, Nakamura H, Matsuhiro Y, Yasumoto K, Tsuda M, Okamoto N, Matsunaga-Lee Y, Egami Y, Tanouchi J, Yamada T, Yasumura Y, Tamaki S, Hayashi T, Nakagawa A, Nakagawa Y, Sotomi Y, Nakatani D, Hikoso S, Sakata Y; Osaka CardioVascular Conference (OCVC)-Heart Failure Investigators. Clinical impact of blood urea nitrogen, regardless of renal function, in heart failure with preserved ejection fraction. Int J Cardiol. 2022;363:94-101.
MAHDI EM. The Influences of Aminophylline and Indomethacin in Glycerol-Induced Acute Renal Failure in Rats. Al-Kindy Col Med J. 2010; 6(1): 62-70.
Qi SS, Zheng HX, Jiang H, Yuan LP, Dong LC. Protective Effects of Chromium Picolinate Against Diabetic-Induced Renal Dysfunction and Renal Fibrosis in Streptozotocin-Induced Diabetic Rats. Biomolecules. 2020;10(3):398.
Mozaffari MS, Baban B, Abdelsayed R, Liu JY, Wimborne H, Rodriguez N, Abebe W. Renal and glycemic effects of high-dose chromium picolinate in db/db mice: assessment of DNA damage. J Nutr Biochem. 2012;23(8):977-985.
Piko N, Bevc S, Hojs R, Ekart R. The role of oxidative stress in kidney injury. Antioxidants. 2023; 12(9) :1772.
Abd MR, Hassan AF. The Ameliorative Effect of Fimasartan against Methotrexate-Induced Nephrotoxicity in Rats. Iraqi J Pharm Sci. 2022; 31(1):87–94.
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