Evaluation of the possible protective role of naringenin on gentamicin-induced ototoxicity: A preliminary study

Kocak, Ilker; Saraç, Sarp; Aydoğan, Esra; Şentürk, Erol; Akakın, Dilek; Koroglu, Kutay; Özer, Ömer Faruk

doi:10.1016/j.ijporl.2017.07.008

Cited by 14 publications

(6 citation statements)

References 35 publications

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“…It is also the main first-line medicinal drug for neonates' early infections (Johnson and Messier 2016;Karahan et al 2005). The main side effects of GEN use are ototoxicity and nephrotoxicity (Elsakka et al 2020;Koçak et al 2017). Sodium salicylate (NaS) is a popular anti-inflammatory and Responsible Editor: Mohamed M. Abdel-Daim pain reliever (Wang et al 2008).…”

Section: Introductionmentioning

confidence: 99%

Curcumin attenuates gentamicin and sodium salicylate ototoxic effects by modulating the nuclear factor-kappaB and apoptotic pathways in rats

Abd‐Elhakim

Abdel-Motal

Malhat³

et al. 2022

Environ Sci Pollut Res

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This study aimed to investigate the effectiveness of curcumin (CCM) against gentamicin (GEN) and sodium salicylates (NaS)-induced ototoxic effects in rats. For 15 consecutive days, seven rat groups were given 1 mL/rat physiological saline orally, 1 mL/rat olive oil orally, 50 mg/kg bwt CCM orally, 120 mg/kg bwt GEN intraperitoneally, 300 mg/kg bwt NaS intraperitoneally, CCM+GEN, or CCM+NaS. The distortion product otoacoustic emission measurements were conducted. The rats’ hearing function and balance have been behaviorally assessed using auditory startle response, Preyer reflex, and beam balance scale tests. The serum lipid peroxidation and oxidative stress biomarkers have been measured. Immunohistochemical investigations of the apoptotic marker caspase-3 and the inflammatory indicator nuclear factor kappa (NF-κB) in cochlear tissues were conducted. GEN and NaS exposure resulted in deficit hearing and impaired ability to retain balance. GEN and NaS exposure significantly decreased the reduced glutathione level and catalase activity but increased malondialdehyde content. GEN and NaS exposure evoked pathological alterations in cochlear and vestibular tissues and increased caspase-3 and NF-κB immunoexpression. CCM significantly counteracted the GEN and NaS injurious effects. These outcomes concluded that CCM could be a naturally efficient therapeutic agent against GEN and NaS-associated ototoxic side effects. Graphical abstract

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Section: Introductionmentioning

confidence: 99%

Curcumin attenuates gentamicin and sodium salicylate ototoxic effects by modulating the nuclear factor-kappaB and apoptotic pathways in rats

Abd‐Elhakim

Abdel-Motal

Malhat³

et al. 2022

Environ Sci Pollut Res

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“…Most attempts to identify compounds that could be co-administered with aminoglycosides to provide otoprotection without diminishing bactericidal activity have focussed on testing antioxidants and anti-apoptotic agents (10)(11)(12)(13)(14)(15)(16)(17)(18)(19). Other attempts have screened libraries of FDAapproved drugs (20), or libraries of molecules that interact with ion channels (21).…”

Section: Introductionmentioning

confidence: 99%

Identification of a series of hair-cell MET channel blockers that protect against aminoglycoside-induced ototoxicity

Kenyon¹,

Kirkwood²,

Kitcher³

et al. 2021

JCI Insight

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To identify small molecules that shield mammalian sensory hair cells from the ototoxic side effects of aminoglycoside antibiotics, 10,240 compounds were initially screened in zebrafish larvae selecting those that protected lateral-line hair cells against neomycin and gentamicin. When the 64 hits from this screen were retested in mouse cochlear cultures, 8 protected outer hair cells (OHCs) from gentamicin in vitro without causing hair-bundle damage. These 8 hits share structural features and all block, to varying degrees, the OHC's mechano-electrical transducer (MET) channel, a known route of aminoglycoside entry into hair cells. Further characterisation of one of the strongest MET-channel blockers, UoS-7692, revealed it additionally protects against kanamycin and tobramycin, and does not abrogate the bactericidal activity of gentamicin. UoS-7692 behaves, like the aminoglycosides, as a permeant blocker of the MET channel, significantly reduces gentamicin-Texas Red loading into OHCs, and preserves lateral-line function in neomycin-treated zebrafish. Trans-tympanic injection of UoS-7692 protects mouse OHCs from furosemide/kanamycin exposure in vivo and partially preserves hearing. The results confirm the hair-cell MET channel as a viable target for the identification of compounds that protect the cochlea from aminoglycosides, and provide a series of hit compounds that will inform the design of future otoprotectants.

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“…Only guinea pigs with normal ABR were included and divided randomly into four equal groups (n = 8 for each) where group 1; served as control group, received vehicle of 0.5% CMC orally by gastric gavage daily. Ototoxicity was induced in the other three groups using gentamicin by intraperitoneal (ip) injection at a dosage of 120 mg/kg/day [15] where group 2; served as untreated gentamicin ototoxicity group, group 3; was treated concomitantly with rapamycin suspended in 0.5% CMC [16] in a dose of 0.13 mg/kg/day orally by gastric gavage, group 4; was treated concomitantly with verapamil hydrochloride dissolved in distilled water [17] in a dose of 30mg/kg/day orally by gastric gavage.…”

Section: Animals and Study Designmentioning

confidence: 99%

“…The ABR was reevaluated after completion of the experiment. The animals were ketamine and xylazine anesthetized by intraperitoneal (ip) injection in a dose of (40 mg/kg, ip) and (5mg/ kg) respectively [15] and blood was obtained through intracardiac blood sampling and processed for assay of reduced glutathione and malondialdehyde levels. The animals were sacrificed, and each cochlea was extracted and infiltrated with a fixative solution immediately.…”

Section: Animals and Study Designmentioning

confidence: 99%

Targeting Autophagy Induction as A possible Protective Mechanism by Verapamil Compared to Rapamycin (Sirolimus) Against Gentamicin -Induced Ototoxicity in Guinea Pigs

Eman Elzayat,

Amany A. Abdin,

Sabiha Hedya

et al. 2021

Indian Journal of Forensic Medicine & Toxicology

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Background: Ototoxicity is a harmful feature of the cochlea or auditory nerve and sometimes vestibular apparatus. Gentamicin is known to cause irreversible bilateral ototoxicity. Autophagy induction has been proposed as a target for prevention of gentamicin ototoxicity. Aim of the work: to investigate the possible protective effect of autophagy induction by verapamil compared to rapamycin. Methods: This experiment was conducted on 32 male guinea pigs. At the beginning each animal's hearing status was assessed using auditory brainstem response (ABR) audiometry. Then, they were divided into 4 equal groups: Group 1: control group, Group 2: untreated gentamicin-induced ototoxicity group. Group 3: gentamicin-induced ototoxicity treated concomitantly with rapamycin. Group 4: gentamicin-induced ototoxicity treated concomitantly with verapamil. At the end of the experiment, ABR was repeated then the animals were sacrificed, and blood samples were obtained for assaying of reduced glutathione and malondialdehyde levels. The left cochlea was processed for scanning electron microscope, while the right cochlea was processed for histopathology and LC3-II immunohistochemistry. Results: Verapamil revealed superiority compared to rapamycin proved by significant improvement in ABR, histopathological results, in addition to its antioxidant effect. Conclusion: verapamil could be suggested as a potential therapeutic approach to decrease gentamicin ototoxicity.

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Evaluation of the possible protective role of naringenin on gentamicin-induced ototoxicity: A preliminary study

Cited by 14 publications

References 35 publications

Curcumin attenuates gentamicin and sodium salicylate ototoxic effects by modulating the nuclear factor-kappaB and apoptotic pathways in rats

Curcumin attenuates gentamicin and sodium salicylate ototoxic effects by modulating the nuclear factor-kappaB and apoptotic pathways in rats

Identification of a series of hair-cell MET channel blockers that protect against aminoglycoside-induced ototoxicity

Targeting Autophagy Induction as A possible Protective Mechanism by Verapamil Compared to Rapamycin (Sirolimus) Against Gentamicin -Induced Ototoxicity in Guinea Pigs

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