Abstract | BACKGROUND: HYPOTHESIS: 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.
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Authors | Naif O Al-Harbi, Faisal Imam, Mohammed M Al-Harbi, Othman A Al-Shabanah, Moureq Rashed Alotaibi, Homood M As Sobeai, Muhammad Afzal, Imran Kazmi, Ammar Cherkess Al Rikabi |
Journal | Inflammopharmacology
(Inflammopharmacology)
Vol. 27
Issue 4
Pg. 817-827
(Aug 2019)
ISSN: 1568-5608 [Electronic] Switzerland |
PMID | 30600471
(Publication Type: Journal Article)
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Chemical References |
- Antioxidants
- Flavonoids
- Imidazoles
- NF-kappa B
- Oligopeptides
- Tetrazoles
- Rutin
- carfilzomib
- olmesartan
- Nitric Oxide Synthase
- Caspase 3
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Topics |
- Animals
- Antioxidants
(pharmacology)
- Apoptosis
(drug effects)
- Caspase 3
(metabolism)
- Flavonoids
(pharmacology)
- Imidazoles
(pharmacology)
- Inflammation
(drug therapy, metabolism)
- Kidney
(drug effects, metabolism)
- Male
- NF-kappa B
(metabolism)
- Nitric Oxide Synthase
(metabolism)
- Oligopeptides
(pharmacology)
- Oxidative Stress
(drug effects)
- Rats
- Rats, Wistar
- Rutin
(pharmacology)
- Signal Transduction
(drug effects)
- Tetrazoles
(pharmacology)
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