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Inflammopharmacology. 2019 Jan 1. doi: 10.1007/s10787-018-0550-5. [Epub ahead of print]

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

Author information

1
Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, Post Box 2457, Riyadh, 11431, Kingdom of Saudi Arabia.
2
Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, Post Box 2457, Riyadh, 11431, Kingdom of Saudi Arabia. fimam@ksu.edu.sa.
3
Department of Pharmacology and Toxicology, College of Pharmacy, Al Jauf University, Sakakah, Kingdom of Saudi Arabia.
4
Department of Pharmacology and Toxicology, School of Pharmacy, Glocal University, Saharan Pur, India.
5
Department of Pathology, College of Medicine, King Khalid University Hospital, Riyadh, Kingdom of Saudi Arabia.

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.

KEYWORDS:

Carfilzomib; Histopathology; NF-κB; NOS-2; Nephrotoxicity; Rutin

PMID:
30600471
DOI:
10.1007/s10787-018-0550-5

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