Nephrotoxicity of cisplatin (CP) involves renal oxidative stress and inflammation, and sesamin (a major liganin in many plants) has strong antioxidant and antiinflammatory actions. Therefore, we investigated here the possible mitigative action of sesamin on CP nephrotoxicity in rats. Sesamin was given orally (5 mg/kg/day, 10 days), and on the 7th day, some of the treated rats were injected intraperitoneally with either saline or CP (5 mg/kg). On the 11th day, rats were sacrificed, and blood and urine samples and kidneys were collected for biochemical estimation of several traditional and novel indices of renal damage in plasma and urine, several oxidative and nitrosative indices in kidneys, and assessment of histopathological renal damage. CP significantly and adversely altered all the physiological, biochemical and histopathological indices of renal function measured. Kidneys of CP-treated rats had a moderate degree of necrosis. This was markedly lessened when CP was given simultaneously with sesamin. Sesamin treatment did not significantly alter the renal CP concentration. The results suggested that sesamin had ameliorated CP nephrotoxicity in rats by reversing the CP-induced oxidative stress and inflammation. Pending further pharmacological and toxicological studies sesamin may be considered a potentially useful nephroprotective agent.

Department of Pharmacology College of Medicine Sultan Qaboos University Al Khod Oman

Zobrazit více v PubMed

AL SULEIMANI YM, AL MAHRUQI AS, AL ZA’ABI M, SHALABY A, ASHIQUE M, NEMMAR A, ALI BH. Effect of diesel exhaust particles on renal vascular responses in rats with chronic kidney disease. Environ Toxicol. 2017;32:541–549. doi: 10.1002/tox.22258. PubMed DOI

ALI BH, ABDELRAHMAN AM, AL-SALAM S, SUDHADEVI M, ALMAHRUQI AS, AL-HUSSENI IS, BEEGAM S, DHANASEKARAN S, NEMMAR A, AL-MOUNDHRI M. The effect of sildenafil on cisplatin nephrotoxicity in rats. Basic Clin Pharmacol Toxicol. 2011;109:300–308. doi: 10.1111/j.1742-7843.2011.00724.x. PubMed DOI

ALI BH, AL MOUNDHRI MS. Agents ameliorating or augmenting the nephrotoxicity of CP and other platinum compounds: a review of some recent research. Food Chem Toxicol. 2006;44:1173–1183. doi: 10.1016/j.fct.2006.01.013. PubMed DOI

ALI BH, RAMKUMAR A, MADANAGOPAL TT, WALY MI, TAGELDIN M, AL-ABRI S, FAHIM M, YASIN J, NEMMAR A. Motor and behavioral changes in mice with cisplatin-induced acute renal failure. Physiol Res. 2014;63:35–45. PubMed

ALI BH, AL-MOUNDHRI M, ELDIN MT, NEMMAR A, AL-SIYABI S, ANNAMALAI K. Amelioration of cisplatin-induced nephrotoxicity in rats by tetramethylpyrazine, a major constituent of the Chinese herb Ligusticum wallichi. Exp Biol Med (Maywood) 2008;233:891–896. doi: 10.3181/0711-RM-315. PubMed DOI

ALI BH, AL-SALAM S, AL HUSSEINI IS, AL-LAWATI I, WALY M, YASIN J, FAHIM M, NEMMAR A. Abrogation of cisplatin-induced nephrotoxicity by emodin in rats. Fundam Clin Pharmacol. 2013;27:192–200. doi: 10.1111/j.1472-8206.2011.01003.x. PubMed DOI

ALI BH, AL-SALAM S, AL SULEIMANI Y, AL KALBANI J, AL BAHLANI S, ASHIQUE M, MANOJ P, AL DHAHLI B, AL ABRI N, NASER HT, YASIN J, NEMMAR A, AL ZA’ABI M, HARTMANN C, SCHUPP N. Curcumin ameliorates kidney function and oxidative stress in experimental chronic kidney disease. Basic Clin Pharmacol Toxicol. 2018;122:65–73. doi: 10.1111/bcpt.12817. PubMed DOI

ALI BH, CAHLIKOVÁ L, OPLETAL L, KARACA T, MANOJ P, RAMKUMAR A, AL SULEIMANI YM, AL ZA’ABI M, NEMMAR A, CHOCHOLOUSOVA-HAVLIKOVA L, LOCAREK M, SIATKA T, BLUNDEN G. Effect of aqueous extract and anthocyanins of calyces of Hibiscus sabdariffa (Malvaceae) in rats with adenine-induced chronic kidney disease. J Pharm Pharmacol. 2017;69:1219–1229. doi: 10.1111/jphp.12748. PubMed DOI

BAEK SH, CHA RH, KANG SW, PARK CW, CHA DR, KIM SG, YOON SA, KIM S, HAN SY, PARK JH, CHANG JH, LIM CS, KIM YS, NA KY. Circulating renalase predicts all-cause mortality and renal outcomes in patients with advanced chronic kidney disease. Korean J Intern Med. 2017;34:858–866. doi: 10.3904/kjim.2017.058. doi: 10.3904/kjim.2017.058. PubMed DOI PMC

CRONA DJ, FASO A, NISHIJIMA TF, McGRAW KA, GALSKY MD, MILOWSKY MI. A systematic review of strategies to prevent cisplatin-induced nephrotoxicity. Oncologist. 2017;22:609–619. doi: 10.1634/theoncologist.2016-0319. PubMed DOI PMC

DARWISH MA, ABO-YOUSSEF AM, KHALAF MM, ABO-SAIF AA, SALEH IG, ABDELGHANY TM. Vitamin E mitigates cisplatin-induced nephrotoxicity due to reversal of oxidative/nitrosative stress, suppression of inflammation and reduction of total renal platinum accumulation. J Biochem Mol Toxicol. 2017;31:1–9. doi: 10.1002/jbt.21833. PubMed DOI

DASARI S, TCHOUNWOU PB. Cisplatin in cancer therapy: molecular mechanisms of action. Eur J Pharmacol. 2014;740:364–378. doi: 10.1016/j.ejphar.2014.07.025. PubMed DOI PMC

DEYÀ-MARTÍNEZ À, FORTUNY C, SOLER-PALACÍN P, NETH O, SÁNCHEZ E, MARTÍN-NALDA A, FALCÓN-NEYRA L, VILA A, VALLS A, NOGUERA-JULIAN A. Cystatin C: A Marker for inflammation and renal function among HIV-infected children and adolescents. Pediatr Infect Dis J. 2016;35:196–200. doi: 10.1097/INF.0000000000000960. PubMed DOI

FAN D, YANG Z, LIU FY, JIN YG, ZHANG N, NI J, YUAN Y, LIAO HH, WU QQ, XU M, DENG W, TANG QZ. Sesamin protects against cardiac remodeling via Sirt3/ROS Pathway. Cell Physiol Biochem. 2017a;44:2212–2227. doi: 10.1159/000486026. PubMed DOI

FAN D, YANG Z, YUAN Y, WU QQ, XU M, JIN YG, TANG QZ. Sesamin prevents apoptosis and inflammation after experimental myocardial infarction by JNK and NF-κB pathways. Food Funct. 2017b;8:2875–2885. doi: 10.1039/C7FO00204A. PubMed DOI

FUKUDA N, ZHANG L, KODAMA M, SAKONO M, IDE T, YAMAMOTO K, SUGANO M. Effect of dietary sesamin on metabolic fate of an exogenous linolelaidic acid in perfused rat liver. J Nutr Sci Vitaminol (Tokyo) 1999;45:437–448. doi: 10.3177/jnsv.45.437. PubMed DOI

GUO H, LIU Y, WANG L, ZHANG G, SU S, ZHANG R, ZHANG J, LI A, SHANG C, BI B, LI Z. Alleviation of doxorubicin-induced hepatorenal toxicities with sesamin via the suppression of oxidative stress. Hum Exp Toxicol. 2016;35:1183–1193. doi: 10.1177/0960327115626581. PubMed DOI

HEIDARI-SORESHJANI S, ASADI-SAMANI M, YANG Q, SAEEDI-BOROUJENI A. Phytotherapy of nephrotoxicity-induced by cancer drugs: an updated review. J Nephropathol. 2017;6:254–263. doi: 10.15171/jnp.2017.41. PubMed DOI PMC

HOEK J, BLOEMENDAL KM, Van der VELDEN LA, Van DIESSEN JN, Van WERKHOVEN E, KLOP WM, TESSELAAR M. Nephrotoxicity as a dose-limiting factor in a high-dose CP-based chemoradiotherapy regimen for head and neck carcinomas. Cancers (Basel) 2016;8:E21. doi: 10.3390/cancers8020021. PubMed DOI PMC

KARASAWA T, STEYGER PS. An integrated view of cisplatin-induced nephrotoxicity and ototoxicity. Toxicol Lett. 2015;237:219–227. doi: 10.1016/j.toxlet.2015.06.012. PubMed DOI PMC

KIMOTO Y, NISHINOHARA M, SUGIYAMA A, HARUNA A, TAKEUCHI T. Protective effect of lactoferrin on cisplatin-induced nephrotoxicity in rats. J Vet Med Sci. 2013;75:159–164. doi: 10.1292/jvms.12-0154. PubMed DOI

LATCHA S, JAIMES EA, PATIL S, GLEZERMAN IG, MEHTA S, FLOMBAUM CD. Long-term renal outcomes after CP treatment. Clin J Am Soc Nephrol. 2016;11:1173–1179. doi: 10.2215/CJN.08070715. PubMed DOI PMC

MA L, LI H, ZHANG S, XIONG X, CHEN K, JIANG P, JIANG K, DENG G. Emodin ameliorates renal fibrosis in rats via TGF-β1/Smad signaling pathway and function study of Smurf 2. Int Urol Nephrol. 2018;50:373–382. doi: 10.1007/s11255-017-1757-x. PubMed DOI

MAHENDRA KUMAR C, SINGH SA. Bioactive lignans from sesame (Sesamum indicum L.): evaluation of their antioxidant and antibacterial effects for food applications. J Food Sci Technol. 2015;52:234–241. doi: 10.1007/s13197-014-1334-6. PubMed DOI PMC

MENG H, FU G, SHEN J, SHEN K, XU Z, WANG Y, JIN B, PAN H. Ameliorative effect of daidzein on cisplatin-induced nephrotoxicity in mice via modulation of inflammation, oxidative stress, and cell death. Oxid Med Cell Longev. 2017;2017:3140680. doi: 10.1155/2017/3140680. PubMed DOI PMC

MILLER RP, TADAGAVADI RK, RAMESH G, REEVES WB. Mechanisms of cisplatin nephrotoxicity. Toxins (Basel) 2010;2:2490–2518. doi: 10.3390/toxins2112490. PubMed DOI PMC

MUKHERJI A, ANSARI U, BORGGREFE M, AKIN I, BEHNES M. Clinically relevant biomarkers in acute heart failure: An update. Curr Pharm Biotechnol. 2017;18:482–490. doi: 10.2174/1389201018666170623090817. PubMed DOI

NAKATANI Y, YAGUCHI Y, KOMURA T, NAKADAI M, TERAO K, KAGE-NAKADAI E, NISHIKAWA Y. Sesamin extends lifespan through pathways related to dietary restriction in Caenorhabditis elegans. Eur J Nutr. 2018;57:1137–1146. doi: 10.1007/s00394-017-1396-0. PubMed DOI

NAMIKI M. Nutraceutical functions of sesame: a review. Crit Rev Food Sci Nutr. 2007;47:651–673. doi: 10.1080/10408390600919114. PubMed DOI

NEMATBAKHSH M, PEZESHKI Z, ESHRAGHI JAZI F, MAZAHERI B, MOEINI M, SAFARI T, AZARKISH F, MOSLEMI F, MALEKI M, REZAEI A, SABERI SH, DEHGHANI A, MALEK M, MANSOURI A, GHASEMI M, ZEINALI F, ZAMANI Z, NAVIDI M, JILANCHI S, SHIRDAVANI S, ASHRAFI F. CP-induced nephrotoxicity; protective supplements and gender differences. Asian Pac J Cancer Prev. 2017;18:295–314. PubMed PMC

OJIMA T, NAKAMURA M, NAKAMORI M, KATSUDA M, HAYATA K, MARUOKA S, SHIMOKAWA T, YAMAUE H. Phase I/II trial of chemotherapy with docetaxel, cisplatin, and S-1 for unresectable advanced squamous cell carcinoma of the esophagus. Oncology. 2018;95:116–120. doi: 10.1159/000488861. PubMed DOI

PABLA N, DONG Z. CP nephrotoxicity: mechanisms and renoprotective strategies. Kidney Int. 2008;73:994–1007. doi: 10.1038/sj.ki.5002786. PubMed DOI

PRASAD KN. Multiple dietary antioxidants enhance the efficacy of standard and experimental cancer therapies and decrease their toxicity. Integr Cancer Ther. 2004;3:310–322. doi: 10.1177/1534735404270936. PubMed DOI

QIANG L, YUAN J, SHOUYIN J, YULIN L, LIBING J, JIAN-AN W. Sesamin attenuates lipopolysaccharide-induced acute lung injury by inhibition of TLR4 signaling pathways. Inflammation. 2016;39:467–472. doi: 10.1007/s10753-015-0270-6. PubMed DOI

QUELHAS-SANTOS J, PESTANA M. Plasma renalase in chronic kidney disease: differences and similarities between humans and rats. Curr Hypertens Rev. 2014;10:166–170. doi: 10.2174/1573402111666150108101709. PubMed DOI

ROUSTA AM, MIRAHMADI SM, SHAHMOHAMMADI A, NOURABADI D, KHAJEVAND-KHAZAEI MR, BALUCHNEJADMOJARAD T, ROGHANI M. Protective effect of sesamin in lipopolysaccharide-induced mouse model of acute kidney injury via attenuation of oxidative stress, inflammation, and apoptosis. Immunopharmacol Immunotoxicol. 2018;29:1–7. doi: 10.1080/08923973.2018.1523926. PubMed DOI

SCHLAICH MP, LAMBERT GW, EIKELIS N. Renalase - a potential biomarker for risk of atrial fibrillation? Kardiol Pol. 2018;76:1201–1202. doi: 10.5603/KP.2018.0163. PubMed DOI

SHAHID F, FAROOQUI Z, KHAN F. Cisplatin-induced gastrointestinal toxicity: An update on possible mechanisms and on available gastroprotective strategies. Eur J Pharmacol. 2018;827:49–57. doi: 10.1016/j.ejphar.2018.03.009. PubMed DOI

SHARP CN, SISKIND LJ. Developing better mouse models to study cisplatin-induced kidney injury. Am J Physiol Renal Physiol. 2017;313:F835–F841. doi: 10.1152/ajprenal.00285.2017. PubMed DOI PMC

SHELTON LM, PARK BK, COPPLE IM. Role of Nrf2 in protection against acute kidney injury. Kidney Int. 2013;84:1090–1095. doi: 10.1038/ki.2013.248. PubMed DOI

SKINNER R. Late renal toxicity of treatment for childhood malignancy: risk factors, long-term outcomes, and surveillance. Pediatr Nephrol. 2018;33:215–225. doi: 10.1007/s00467-017-3662-z. PubMed DOI PMC

SOLIMAN MM, ATTIA HF, EL-ELLA GA. Genetic and histopathological alterations induced by cypermethrin in rat kidney and liver: Protection by sesame oil. Int J Immunopathol Pharmacol. 2015;28:508–520. doi: 10.1177/0394632015575950. PubMed DOI

TOMIMORI N, ROGI T, SHIBATA H. Absorption, distribution, metabolism, and excretion of [(14) C] sesamin in rats. Mol Nutr Food Res. 61:2017. doi: 10.1002/mnfr.201600844. PubMed DOI

WAN Y, LI H, FU G, CHEN X, CHEN F, XIE M. The relationship of antioxidant components and antioxidant activity of sesame seed oil. J Sci Food Agric. 2015;95:2571–2578. doi: 10.1002/jsfa.7035. PubMed DOI

WILMES A, BIELOW C, RANNINGER C, BELLWON P, ASCHAUER L, LIMONCIEL A, CHASSAIGNE H, KRISTL T, AICHE S, HUBER CG, GUILLOU C, HEWITT P, LEONARD MO, DEKANT W, BOIS F, JENNINGS P. Mechanism of cisplatin proximal tubule toxicity revealed by integrating transcriptomics, proteomics, metabolomics and biokinetics. Toxicol In Vitro. 2015;30:117–127. doi: 10.1016/j.tiv.2014.10.006. PubMed DOI

ZHU S, PABLA N, TANG C, HE L, DONG Z. DNA damage response in cisplatin-induced nephrotoxicity. Arch Toxicol. 2015;89:2197–2205. doi: 10.1007/s00204-015-1633-3. PubMed DOI PMC

The Salutary Effects of Diminazene, Lisinopril or Valsartan on Cisplatin - Induced Acute Kidney Injury in Rats: A Comparative Study