Curcumin protects rats against gentamicin-induced nephrotoxicity by amelioration of oxidative stress, endoplasmic reticulum stress and apoptosis.

Publisher: Taylor & Francis Country of Publication: England NLM ID: 9812552 Publication Model: Print Cited Medium: Internet ISSN: 1744-5116 (Electronic) Linking ISSN: 13880209 NLM ISO Abbreviation: Pharm Biol Subsets: MEDLINE

Publication: [London] : Taylor & Francis
Original Publication: Lisse, the Netherlands : Swets & Zeitlinger, c1998-

Antioxidants/*pharmacology ; Curcumin/*pharmacology ; Gentamicins/*toxicity ; Kidney Diseases/*prevention & control; Animals ; Anti-Bacterial Agents/toxicity ; Antioxidants/administration & dosage ; Apoptosis/drug effects ; Creatinine/blood ; Curcumin/administration & dosage ; Dose-Response Relationship, Drug ; Endoplasmic Reticulum Stress/drug effects ; Kidney Diseases/chemically induced ; Male ; Oxidative Stress/drug effects ; Rats ; Rats, Sprague-Dawley ; Superoxide Dismutase/metabolism

Context: Gentamicin (GM) is an aminoglycoside antibiotic which is commonly used against Gram-negative bacterial infection; however, serious complications including nephrotoxicity could limit its clinical use.
Objective: The present study examined the protective effects of curcumin (CUR) on endoplasmic reticulum (ER) stress-mediated apoptosis through its antioxidative property in GM-induced nephrotoxicity in rats.
Materials and Methods: Male Sprague-Dawley rats ( n  = 3) were divided into six groups to receive normal saline (control), GM (100 mg/kg/day), co-treatment with GM and CUR (100, 200 and 300 mg/kg/day) and CUR (200 mg/kg/day) alone for 15 days by gavage feeding. Then, the renal function, kidney injury as well as oxidative stress, antioxidative markers and ER stress-mediated apoptosis were evaluated.
Results: Pre-treatment of CUR rescued the nephrotoxicity in GM-treated rats. Several nephrotoxicity hallmarks were reversed in the CUR-pre-treatment group. At the dose of 200 mg/kg/day, it could significantly lower serum creatinine (from 0.95 to 0.50 mg/dL), blood urea nitrogen (from 35.00 to 23.50 mg/dL) and augmented creatinine clearance (from 0.83 to 1.71 mL/min). The normalized expression of oxidative stress marker, malondialdehyde was decreased (from 13.00 to 5.98) in line with the increase of antioxidant molecules including superoxide dismutase (from 5.59 to 14.24) and glutathione (from 5.22 to 12.53). Furthermore, the renal ER stress and apoptotic protein biomarkers were lowered in CUR treatment.
Discussion and Conclusions: Our findings pave the way for the application of CUR as a supplement in the prevention of nephrotoxicity and other kidney diseases in the future.

Kidney Int. 2011 Jan;79(1):33-45. (PMID: 20861826)
J Pharm Pharmacol. 1997 Jan;49(1):105-7. (PMID: 9120760)
Int J Clin Exp Med. 2015 Oct 15;8(10):18225-34. (PMID: 26770424)
Scand J Clin Lab Invest Suppl. 2008;241:78-83. (PMID: 18569971)
Kidney Int. 2005 Jun;67(6):2239-53. (PMID: 15882266)
Med Sci Monit. 2007 Mar;13(3):BR73-83. (PMID: 17325631)
Biochim Biophys Acta. 2015 Jan;1852(1):70-82. (PMID: 25446996)
Antioxid Redox Signal. 2007 Dec;9(12):2277-93. (PMID: 17979528)
Yakugaku Zasshi. 2006 May;126(5):327-35. (PMID: 16679740)
Oxid Med Cell Longev. 2012;2012:269039. (PMID: 22919438)
PLoS One. 2016 Oct 11;11(10):e0164528. (PMID: 27727327)
J Cell Biol. 2000 Aug 21;150(4):887-94. (PMID: 10953012)
Food Chem Toxicol. 2006 Sep;44(9):1443-8. (PMID: 16814915)
Eur J Pharmacol. 2002 Aug 16;450(1):67-76. (PMID: 12176111)
Free Radic Biol Med. 2000 Oct 1;29(7):602-11. (PMID: 11033412)
Redox Biol. 2013 Sep 17;1:448-56. (PMID: 24191240)
Exp Toxicol Pathol. 2012 Jan;64(1-2):69-74. (PMID: 20619622)
Free Radic Res. 2015 Mar;49(3):279-89. (PMID: 25536420)
Mayo Clin Proc. 1999 May;74(5):519-28. (PMID: 10319086)
Fundam Clin Pharmacol. 2011 Dec;25(6):708-16. (PMID: 21105912)
J Biol Chem. 2006 Oct 6;281(40):30036-45. (PMID: 16893887)
Am J Physiol Renal Physiol. 2004 Mar;286(3):F552-63. (PMID: 14600030)
Int Urol Nephrol. 2010 Mar;42(1):141-50. (PMID: 19582588)
PLoS One. 2013 Dec 13;8(12):e83349. (PMID: 24349491)
Biol Pharm Bull. 2009 Jan;32(1):61-7. (PMID: 19122282)
Cell Calcium. 2002 Nov-Dec;32(5-6):235-49. (PMID: 12543086)
Methods Mol Biol. 2009;559:191-204. (PMID: 19609758)
Acta Physiol (Oxf). 2013 Apr;207(4):663-72. (PMID: 23375078)
Food Chem Toxicol. 2008 Sep;46(9):3193-9. (PMID: 18692113)
Anal Biochem. 1979 Jun;95(2):351-8. (PMID: 36810)
Tissue Cell. 2011 Dec;43(6):392-7. (PMID: 22000907)
Cancer Lett. 1995 Jul 20;94(1):79-83. (PMID: 7621448)
J Pharmacol Sci. 2016 Nov;132(3):192-200. (PMID: 27840063)
Oncogene. 1997 Oct 9;15(15):1763-72. (PMID: 9362442)
J Biol Chem. 1998 Mar 27;273(13):7770-5. (PMID: 9516487)
Planta Med. 1991 Feb;57(1):1-7. (PMID: 2062949)
Antioxid Redox Signal. 2009 Sep;11(9):2307-16. (PMID: 19309259)
Nephron. 1976;16(1):31-41. (PMID: 1244564)
Kidney Blood Press Res. 2016;41(6):911-918. (PMID: 27889773)
Free Radic Biol Med. 2003 Sep 1;35(5):475-84. (PMID: 12927597)
Transplant Rev (Orlando). 2010 Jul;24(3):143-6. (PMID: 20447817)
Toxicol Appl Pharmacol. 2009 Aug 1;238(3):306-14. (PMID: 19371613)
Neurosci Lett. 2004 Mar 4;357(2):127-30. (PMID: 15036591)
Chem Soc Rev. 2015 Aug 7;44(15):4986-5002. (PMID: 25964104)
Circ Res. 2004 Nov 12;95(10):957-70. (PMID: 15539639)
Kidney Int. 2002 Nov;62(5):1682-92. (PMID: 12371968)
Nephrol Dial Transplant. 1994;9 Suppl 4:135-40. (PMID: 7800247)
J Adv Pharm Technol Res. 2019 Jul-Sep;10(3):95-99. (PMID: 31334089)
Pharmacol Res. 2010 Sep;62(3):179-86. (PMID: 20434560)
Drug Metab Rev. 2005;37(3):405-42. (PMID: 16257829)
J Cell Biol. 2000 Aug 21;150(4):731-40. (PMID: 10952999)
J Pathol. 2010 Feb;220(3):328-37. (PMID: 19950250)
Int J Mol Sci. 2019 Oct 22;20(20):. (PMID: 31652595)
Drug Metab Pharmacokinet. 2004 Jun;19(3):159-70. (PMID: 15499183)
Int J Mol Sci. 2016 Nov 01;17(11):. (PMID: 27809280)
Free Radic Res. 2011 Oct;45(10):1223-31. (PMID: 21781008)
EMBO Rep. 2006 Sep;7(9):880-5. (PMID: 16953201)

Keywords: Oxidative damage; natural antioxidant; renoprotective

0 (Anti-Bacterial Agents)
0 (Antioxidants)
0 (Gentamicins)
AYI8EX34EU (Creatinine)
EC 1.15.1.1 (Superoxide Dismutase)
IT942ZTH98 (Curcumin)

Date Created: 20220221 Date Completed: 20220316 Latest Revision: 20220501

20231215

PMC8865128

10.1080/13880209.2022.2037663

35188833