nach oben

Inflammopharmacology

Erschienen in:

01.01.2019 | Original Article

Rutin inhibits carfilzomib-induced oxidative stress and inflammation via the NOS-mediated NF-κB signaling pathway

Erschienen in: Inflammopharmacology | Ausgabe 4/2019

Einloggen, um Zugang zu erhalten

Abstract

Background

Carfilzomib (CFZ), a proteasome inhibitor approved by the FDA to treat multiple myeloma, may cause nephrotoxicity.

Hypothesis

Rutin is a bioflavonoid with antioxidant properties. We aimed to examine whether rutin protects the kidney from CFZ-induced nephrotoxicity.

Study design

This study aimed to demonstrate the effect of rutin on CFZ-induced renal injury via the inhibition of oxidative stress and inflammation.

Methods

Wistar albino rats were divided into six groups (n = 6): Group 1 (normal control; NC) was administered normal saline for 3 weeks; Group 2 (CFZ/toxic group) received CFZ [4 mg/kg, intraperitoneal (i.p.) injection] twice weekly for 3 weeks; Group 3 (standard treatment group) was administered CFZ (4 mg/kg, i.p.) and olmesartan (2 mg/kg, p.o.) for 3 weeks; Group 4 was administered CFZ (4 mg/kg, i.p.) and rutin (10 mg/kg, p.o.) for 3 weeks; Group 5 was administered CFZ (4 mg/kg, i.p.) and rutin (20 mg/kg, p.o.) for 3 weeks; and Group 6 was administered CFZ (4 mg/kg, i.p.) and rutin (40 mg/kg, p.o.) for 3 weeks. We carried out haematological and biochemical analyses, determined oxidative stress, caspase-3 activity, and protein levels, and performed a histopathological evaluation to confirm CFZ-induced nephrotoxicity and its prevention by rutin administration.

Results

Exposure to only CFZ significantly (p < 0.05) increased white blood cell (WBC) count, Hb%, and HTC% concentration; however, these features were significantly decreased (p < 0.05) when olmesartan and rutin were administered. CFZ administration significantly decreased (p < 0.0001) the level of antioxidant enzymes; whereas, administration of olmesartan and rutin significantly reversed (p < 0.05) their levels toward the normal range. The levels of caspase-3 enzyme significantly increased (p < 0.001) in the CFZ group and were reduced toward the normal values by olmesartan and rutin administration. Furthermore, the results of NOS-2, NF-κB, IkBa, and IL-17 protein estimation and the histopathological evaluation strengthened our findings that rutin exhibits a protective effect against CFZ-induced nephrotoxicity.

Conclusion

These findings clearly demonstrate that rutin ameliorates CFZ-induced oxidative stress and inflammation in nephrotoxicity via the NOS-mediated NF-κB signaling pathway.

Abarikwu SO, Adebayo OL, Otuechere CA, Iserhienrhien BO, Badejo TA (2016) Selenium and rutin alone or in combination do not have stronger protective effects than their separate effects against cadmium-induced renal damage. Pharm Biol. 54:896–904CrossRefPubMed

Al-Harbi NO (2016) Carfilzomib-induced cardiotoxicity mitigated by dexrazoxane through inhibition of hypertrophic gene expression and oxidative stress in rats. Toxicol Mech Methods 26:189–195CrossRefPubMed

Al-Harbi NO, Imam F, Al-Harbi MM, Iqbal M, Nadeem A, Sayed-Ahmed MM, Alabidy AD, Almukhallafi AF (2014) Olmesartan attenuates tacrolimus-induced biochemical and ultrastructural changes in rat kidney tissue. Biomed Res Int 2014:1–7CrossRef

Al-Harbi NO, Imam F, Al-Harbi MM, Ansari MA, Zoheir KM, Korashy HM, Sayed-Ahmed MM, Attia SM, Shabanah OA, Ahmad SF (2016) Dexamethasone attenuates LPS-induced acute lung injury through inhibition of Nf-κb, Cox-2, and pro-inflammatory mediators. Immunol Invest 45:349–369CrossRefPubMed

Altinterim B (2014) Citrus, rutin and on their vein permeability effects. RJAEM 3:80–81

Badros AZ, Vij R, Martin T, Zonder JA, Kunkel L, Wang Z, Lee S, Wong AF, Niesvizky R (2013) Carfilzomib in multiple myeloma patients with renal impairment: pharmacokinetics and safety. Leukemia 27:1707–1714CrossRefPubMedPubMedCentral

BenaventeGarcia O, Castillo J (2008) Update on uses and properties of citrus flavonoids: new findings in anticancer, cardiovascular, and antiinflammatory activity. J Agric Food Chem 56:6185–6205CrossRef

Carlberg I, Mannervik B (1985) Glutathione reductase. Methods Enzymol 113:484–490CrossRefPubMed

Claiborne A (1985) Catalase activity. In: Greenwald RA (ed) CRC handbook of methods for oxygen radical research. CRC Press Inc, Boca Raton, pp 283–284

Cuzzocrea S, Mazzon E, Dugo L, Serraino I, Di-Paola R, Britti D, De Sarro A, Pierpaoli S, Caputi A, Masini E, Salvemini D (2002) A role for superoxide in gentamicin-mediated nephropathy in rats. Eur J Pharmacol 450:67–76CrossRefPubMed

Demo SD, Kirk CJ, Aujay MA, Buchholz TJ, Dajee M, Ho MN, Jiang J, Laidig GJ, Lewis ER, Parlati F, Shenk KD, Smyth MS, Sun CM, Vallone MK, Woo TM, Molineaux CJ, Bennett MK (2007) Antitumor activity of PR171, a novel irreversible inhibitor of the proteasome. Cancer Res 67:6383–6391CrossRefPubMed

Dowling TC, Briglia AE, Fink JC, Hanes DS, Light PD, Stackiewicz L et al (2003) Characterization of hepatic cytochrome P 450 3A activity in patients with end-stage renal disease. J Clin Exp Pharmacol 73:427–434

El-Shitany NA, El-Haggar S, El-Desoky K (2008) Silymarin prevent adriamycin-induced cardiomyopathy and nephropathy in rats. Food Chem Toxicol 46:2422–2428CrossRefPubMed

Farooqui Z, Ahmed F, Rizwan S, Shahid F, Khan AA, Khan F (2017) Protective effect of Nigella sativa oil on cisplatin induced nephrotoxicity and oxidative damage in rat kidney. Biomed Pharmacother 85:7–15CrossRefPubMed

Fuchs O, Provaznikova D, Marinov I, Kuzelova K, Spicka I (2009) Antiproliferative and proapoptotic effects of proteasome inhibitors and their combination with histone deacetylase inhibitors on leukemia cells. Cardiovasc Hematol Disord Drug Targets 9:62–77CrossRefPubMed

Hajek R, Bryce R, Ro S, Klencke B, Ludwig H (2012) Design and rationale of FOCUS (PX171011): a randomized, openlabel, phase 3 study of carfilzomib versus best supportive care regimen in patients with relapsed and refractory multiple myeloma (R/R MM). BMC Cancer 12:415–521CrossRefPubMedPubMedCentral

Harvey RD (2014) Incidence and management of adverse events in patients with relapsed and/or refractory multiple myeloma receiving single-agent carfilzomib. Clin Pharmacol 6:87–96PubMedPubMedCentral

Heather S, Demrow BS, Peter R, Slane BS, John DF (1995) Administration of wine and grape juice inhibits in vivo platelet activity and thrombosis in stenosed canine coronary arteries. Am Heart Assoc 91:1182–1188

Herndon TM, Deisseroth A, Kaminskas E, Kane RC, Koti KM, Rothmann MD, Rothmann MD, Habtemariam B, Bullock J, Bray JD, Hawes J, Palmby TR, Jee J, Adams W, Mahayni H, Brown J, Dorantes A, Sridhara R, Farrell AT, Pazdur R (2013) Food and drug administration approval: carfilzomib for the treatment of multiple myeloma. Clin Cancer Res 19(17):4559–4563CrossRefPubMed

Hobeika L, Self SE, Velez JCQ (2014) Renal thrombotic microangiopathy and podocytopathy associated with the use of carfilzomib in a patient with multiple myeloma. BMC Nephrol 15:1–6CrossRef

Humanes B, Jado J, Camaño S, López-Parra V, Torres A, Álvarez-Sala L, Cercenado E, Tejedor A, Lázaro A (2015) Protective effects of cilastatin against vancomycin-induced nephrotoxicity. Biomed Res Int 2015:1–12CrossRef

Ibrahim MA, Ashour OM, Ibrahim YF, El-Bitar HI, Gomaa W, Abdel-Rahim SR (2009) Angiotensin-converting enzyme inhibition and angiotensin AT1-receptor antagonism equally improve doxorubicin-induced cardiomyopathy and nephropathy. Pharmacol Res 60:373–381CrossRefPubMed

Imam F, Al-Harbi NO, Al-Harbi MM, Ansari MA, Almutairi MM, Alshammari M, Almukhlafi TS, Ansari MN, Aljerian K, Ahmad SF (2016) Apremilast reversed carfilzomib-induced cardiotoxicity through inhibition of oxidative stress, NF-κB and MAPK signaling in rats. Toxicol Mech Methods 26:700–708CrossRefPubMed

Imam F, Al-Harbi NO, Al-Harbi MM, Korashy HM, Ansari MA, Sayed-Ahmed MM, Nagi MN, Iqbal M, Khalid Anwer M, Kazmi I, Afzal M, Bahashwan S (2017) Rutin attenuates carfilzomib-induced cardiotoxicity through inhibition of NF-κB, hypertrophic gene expression and oxidative stress. Cardiovasc Toxicol 17:58–66CrossRefPubMed

Kadowaki D, Anraku M, Tasaki Y, Taguchi K, Shimoishi K, Seo H, Hirata S, Maruyama T, Otagiri M (2009) Evaluation for antioxidant and renoprotective activity of olmesartan using nephrectomy rats. Biol Pharm Bull 32(12):2041–2045CrossRefPubMed

Khan RZ, Badros A (2012) Role of carfilzomib in the treatment of multiple myeloma. Rev Hematol 5:361–372CrossRef

Khanna AK, Pieper GM (2007) NADPH oxidase subunits (NOX-1, p22phox, Rac-1) and tacrolimus-induced nephrotoxicity in a rat renal transplant model. Nephrol Dial Transplant 22:376–385CrossRefPubMed

Liberman V, D’Agati VD, Naveed NM, Drakakis J, Mattana J (2016) Acute tubular necrosis in a patient with myeloma treated with carfilzomib. Kidney Int Rep 1:89–92CrossRefPubMedPubMedCentral

Lowry OH, Rosenburg NJ, Farr AL, Randall RJ (1951) Protein measurement with Folin phenol reagent. J Biol Chem 193:265–275

McBride L, Samuel CO (2013) The side effect profile of carfilzomib: from clinical trials to clinical practice. J Adv Pract Oncol 4:22–30

Nathan C, Xie QW (1994) Regulation of biosynthesis of nitric oxide. J Biol Chem 269(19):13725–13728PubMed

Nooka AK (2013) Management of hematologic adverse events in patients with relapsed and/or refractory multiple myeloma treated with single-agent carfilzomib. Oncology (Williston Park) 27:11–18

Ohkawa H, Ohishi N, Yagi K (1979) Assay for lipid peroxides in animal tissues by thiobarbituric acid reaction. Anal Biochem 95:351–358CrossRef

Panchal SK, Poudyal H, Arumugam TV, Brown L (2011) Rutin attenuates metabolic changes, nonalcoholic steatohepatitis, and cardiovascular remodeling in highcarbohydrate, high fat diet fed rats. J Nutr 141:1062–1069CrossRefPubMed

Panchal SK, Poudyal H, Brown L (2012) Quercetin ameliorates cardiovascular, hepatic, and metabolic changes in DIET-induced metabolic syndrome in rats. J Nutr 142:1026–1032CrossRefPubMed

Pavenstadt H, Kriz W, Kretzler M (2003) Cell biology of the glomerular podocyte. Physiol Rev 83:253–307CrossRefPubMed

Porter GA, Palmer BF, Henrich WL (2003) Clinical relevance. In: DeBroe ME, Porter GA, Bennett WM, Verpooten GA (eds) Clinical nephrotoxins: renal injury from drugs and chemicals. Kluwer Academic Publishers, Dordrecht, pp 3–20CrossRef

Radwan RR, Abdel-Fattah SM (2017) Mechanisms involved in the possible nephroprotective effect of rutin and low dose γ irradiation against cisplatin-induced nephropathy in rats. J Photochem Photobiol B Biol 169:56–62CrossRef

Sahu BD, Tatireddy S, Koneru M, Borkar RM, Jerald MK, Kuncha M, Srinivas R, Shyam Sunder R, Sistla R (2014) Naringin ameliorates gentamicin-induced nephrotoxicity and associated mitochondrial dysfunction, apoptosis and inflammation in rats: possible mechanism of nephroprotection. Toxicol Appl Pharmacol 277:8–20CrossRefPubMed

Sedlak J, Lindsay RH (1968) Estimation of total, protein bound and non-protein bound sulfhydryl groups in tissue with Ellman’s reagent. Anal Biochem 25:192–205CrossRef

Siegel DS (2013) From clinical trials to clinical practice: single-agent carfilzomib adverse events and their management in patients with relapsed and/or refractory multiple myeloma. Ther Adv Hematol 4:354–365CrossRefPubMedPubMedCentral

Siegel D, Martin T, Nooka A, Harvey RD, Vij R, Niesvizky R, Badros AZ, Jagannath S, McCulloch L, Rajangam K, Lonial S (2013) Integrated safety profile of single-agent carfilzomib: experience from 526 patients enrolled in 4 phase II clinical studies. Haematologica 98:1753–1761CrossRefPubMedPubMedCentral

Suzuki K, Ri M, Chou T, Sugiura I, Takezako N, Sunami K, Ishida T, Izumi T, Ozaki S, Shumiya Y, Ota K, Iida S (2017) Carfilzomib, lenalidomide and dexamethasone in patients with heavily pretreated multiple myeloma: a phase 1 study in Japan. Cancer Sci 108:461–468CrossRefPubMedPubMedCentral

Vij R, Siegel DS, Jagannath S, Jakubowiak AJ, Stewart AK, McDonagh K, Bahlis N, Belch A, Kunkel LA, Wear S, Wong AF, Wang M (2012) An openlabel, singlearm, phase 2 study of single agent carfilzomib in patients with relapsed and/or refractory multiple myeloma who have been previously treated with bortezomib. Br J Haematol 158:739–748CrossRefPubMedPubMedCentral

Wanchoo R, Khan S, Kolitz JE, Jhaveri KD (2015) Carfilzomib-related acute kidney injury may be prevented by N-acetyl-l-cysteine. J Oncol Pharm Pract 21:313–316CrossRefPubMed

Wang M, Martin T, Bensinger W, Alsina M, Siegel DS, Kavalerchik E, Huang M, Orlowski RZ, Niesvizky R (2013) Phase 2 dose-expansion study (PX-171-006) of carfilzomib, lenalidomide, and low-dose dexamethasone in relapsed or progressive multiple myeloma. Blood 122:3122–3128CrossRefPubMedPubMedCentral

Wang B, Liu D, Zhu QH, Li M, Chen H, Guo Y, Fan LP, Yue LS, Li LY, Zhao M (2016a) Rutin ameliorates kidney interstitial fibrosis in rats with obstructive nephropathy. Int Immunopharmacol 35:77–84CrossRefPubMed

Wang X, Zhao X, Feng T, Jin G, Li Z (2016b) Rutin prevents high glucose-induced renal glomerular endothelial hyperpermeability by inhibiting the ROS/Rhoa/ROCK signaling pathway. Planta Med 82:1252–1257CrossRefPubMed

Titel: Rutin inhibits carfilzomib-induced oxidative stress and inflammation via the NOS-mediated NF-κB signaling pathway
Publikationsdatum: 01.01.2019
Erschienen in: Inflammopharmacology / Ausgabe 4/2019
Print ISSN: 0925-4692
Elektronische ISSN: 1568-5608
DOI: https://doi.org/10.1007/s10787-018-0550-5

Springer Medizin

Abstract

Background

Hypothesis

Study design

Methods

Results

Conclusion

Bitte loggen Sie sich ein, um Zugang zu diesem Inhalt zu erhalten

Weitere Artikel der Ausgabe 4/2019

Protective effect of isoliquiritigenin against cerebral injury in septic mice via attenuation of NF-κB

Antinociceptive activity of Copaifera officinalis Jacq. L oil and kaurenoic acid in mice

4-Phenylbutyric acid protects against vasculitic peripheral neuropathy induced by ischaemia–reperfusion through attenuating endoplasmic reticulum stress

Aberrant up-regulation of iNOS/NO system is correlated with an increased abundance of Foxp3+ cells and reduced effector/memory cell markers expression during colorectal cancer: immunomodulatory effects of cetuximab combined with chemotherapy

Ginsenoside compound-K inhibits the activity of B cells through inducing IgD-B cell receptor endocytosis in mice with collagen-induced arthritis

Efficacy of punarnavine in restraining organ-specific tumour progression in 4T1-induced murine breast tumour model