Neurotrophic and antioxidant effects of silymarin comparable to 4-methylcatechol in protection against gentamicin-induced ototoxicity in guinea pigs

Draz, Eman I.; Abdin, Amany A.; Sarhan, Naglaa I.; Gabr, Takwa A.

doi:10.1016/j.pharep.2014.10.007

Cited by 17 publications

(7 citation statements)

References 61 publications

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“…At the start point, there was non-significant variation between groups with normal ABR in all animals, while at the end point there was significantly increased ABR threshold compared to the start one. Our results in group 2 compared to group 1 showed absence of ABR response in 75% of animals indicating sever hearing loss, while others showed significant increase in wave III latency, wave V latency and significant ABR threshold increase which coincides with many studies [5,22,29] . The ABR results are matched with histopathology in light and SEM where there are variable degrees of HCs death, pathological changes in stria vascularis and degeneration of spiral ganglion which are in line with many studies [22,30,31] .…”

Section: Discussionsupporting

confidence: 90%

“…Our results in group 2 compared to group 1 showed absence of ABR response in 75% of animals indicating sever hearing loss, while others showed significant increase in wave III latency, wave V latency and significant ABR threshold increase which coincides with many studies [5,22,29] . The ABR results are matched with histopathology in light and SEM where there are variable degrees of HCs death, pathological changes in stria vascularis and degeneration of spiral ganglion which are in line with many studies [22,30,31] . ROS role in gentamicin ototoxicity is documented in different studies [32,33] .…”

Section: Discussionsupporting

confidence: 90%

“…Fenestration was made at left cochlear apex for infiltration with 2.5% glutaraldehyde. The cochlea was processed for examination then dried using critical point dryer then examined with a JEOL (SEM) [22] .…”

Section: Scanning Electron Microscope (Sem)mentioning

confidence: 99%

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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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Section: Discussionsupporting

confidence: 90%

Section: Discussionsupporting

confidence: 90%

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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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“…However, these aminoglycoside drugs also continue to be used in view of their cost and effectiveness, and their ototoxicity usually limits the dose range of drugs [4,6]. GM is a cationic aminoglycoside that enters cells via endocytosis and forms a complex with iron, which drives the formation of free radicals and directly promotes the formation of ROS [7]. Recent reports show that antioxidant drugs can benefit patients with hearing loss, because hearing loss is produced by excessive generation of reactive oxygen species (ROS) in cells of the cochlea [8,9].…”

Section: Introductionmentioning

confidence: 99%

Structure Characterization and Otoprotective Effects of a New Endophytic Exopolysaccharide from Saffron

Qin

et al. 2019

Molecules

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Saffron, a kind of rare medicinal herb with antioxidant, antitumor, and anti-inflammatory activities, is the dry stigma of Crocus sativus L. A new water-soluble endophytic exopolysaccharide (EPS-2) was isolated from saffron by anion exchange chromatography and gel filtration. The chemical structure was characterized by FT-IR, GC-MS, and 1D and 2D-NMR spectra, indicating that EPS-2 has a main backbone of (1→2)-linked α-d-Manp, (1→2, 4)-linked α-d-Manp, (1→4)-linked α-d-Xylp, (1→2, 3, 5)-linked β-d-Araf, (1→6)- linked α-d-Glcp with α-d-Glcp-(1→ and α-d-Galp-(1→ as sidegroups. Furthermore, EPS-2 significantly attenuated gentamicin-induced cell damage in cultured HEI-OC1 cells and increased cell survival in zebrafish model. The results suggested that EPS-2 could protect cochlear hair cells from ototoxicity exposure. This study could provide new insights for studies on the pharmacological mechanisms of endophytic exopolysaccharides from saffron as otoprotective agents

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“…Silymarin (SM) is a flavonolignan mixture derived from the seeds of Silybum marianum L. Gaertn (milk thistle), with silybin as its main component (70%–80%) [1]. SM has been widely used as a hepatoprotective agent for a variety of acute and chronic liver diseases, due to its therapeutic effect based on its antioxidant [2], anti-inflammatory [3], immunomodulatory [4] and anti-viral activities [5]. Previous reports have shown that the efficacy of oral SM on liver function and chronic hepatitis C virus (HCV) load was low, due to its low bioavailability, extensive first pass metabolism and short life of flavonoids [6].…”

Section: Introductionmentioning

confidence: 99%

Silymarin-Loaded Nanoparticles Based on Stearic Acid-Modified Bletilla striata Polysaccharide for Hepatic Targeting

et al. 2016

Molecules

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Silymarin has been widely used as a hepatoprotective drug in the treatment of various liver diseases, yet its effectiveness is affected by its poor water solubility and low bioavailability after oral administration, and there is a need for the development of intravenous products, especially for liver-targeting purposes. In this study, silymarin was encapsulated in self-assembled nanoparticles of Bletilla striata polysaccharide (BSP) conjugates modified with stearic acid and the physicochemical properties of the obtained nanoparticles were characterized. The silymarin-loaded micelles appeared as spherical particles with a mean diameter of 200 nm under TEM. The encapsulation of drug molecules was confirmed by DSC thermograms and XRD diffractograms, respectively. The nanoparticles exhibited a sustained-release profile for nearly 1 week with no obvious initial burst. Compared to drug solutions, the drug-loaded nanoparticles showed a lower viability and higher uptake intensity on HepG2 cell lines. After intravenous administration of nanoparticle formulation for 30 min to mice, the liver became the most significant organ enriched with the fluorescent probe. These results suggest that BSP derivative nanoparticles possess hepatic targeting capability and are promising nanocarriers for delivering silymarin to the liver.

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Neurotrophic and antioxidant effects of silymarin comparable to 4-methylcatechol in protection against gentamicin-induced ototoxicity in guinea pigs

Abstract: Silymarin exerts superiority over 4-methylcatechol when recommended as protective agent against gentamicin ototoxicity based on its efficient neurotrophic and antioxidant activities.

Cited by 17 publications

References 61 publications

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

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

Structure Characterization and Otoprotective Effects of a New Endophytic Exopolysaccharide from Saffron

Silymarin-Loaded Nanoparticles Based on Stearic Acid-Modified Bletilla striata Polysaccharide for Hepatic Targeting

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