The Antioxidant Effect of Rosmarinic Acid by Different Delivery Routes in the Animal Model of Noise-Induced Hearing Loss

Fetoni, Anna Rita; Eramo, Sara Letizia Maria; Pino, Antonella; Rolesi, Rolando; Paciello, Fabiola; Grassi, Claudio; Troiani, Diana; Paludetti, Gaetano

doi:10.1097/mao.0000000000001700

Cited by 22 publications

(10 citation statements)

References 36 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In the inner ear, many antioxidants, such as rosmarinic acid [25], alpha-lipoic acid [26], and Mitoquinone [27] have been applied to improve hearing loss after exposure to various damage, such as noise or ototoxic drugs. ATX, which has a stronger biological activity than other antioxidants because of its link with the cell membrane from the inside to the outside [28], has been shown to protect against CDDP-induced nephrotoxicity in rats [29] and neomycin-induced ototoxicity in zebrafish hair cells [30].…”

Section: Discussionmentioning

confidence: 99%

Astaxanthin-loaded polymer-lipid hybrid nanoparticles (ATX-LPN): assessment of potential otoprotective effects

Chen

Tong

et al. 2020

J Nanobiotechnol

View full text Add to dashboard Cite

Background: Ototoxicity is one of the major side effects of platinum-based chemotherapy, especially cisplatin therapy. To date, no FDA approved agents to alleviate or prevent this ototoxicity are available. However, ototoxicity is generally believed to be produced by excessive generation of reactive oxygen species (ROS) in the inner ear, thus leading to the development of various antioxidants, which act as otoprotective agents. Astaxanthin (ATX) is an interesting candidate in the development of new therapies for preventing and treating oxidative stress-related pathologies, owing to its unique antioxidant capacity. Methods and results:In this study, we aimed to evaluate the potential antioxidant properties of ATX in the inner ear by using the HEI-OC1 cell line, zebrafish, and guinea pigs. Because ATX has poor solubility and cannot pass through round window membranes (RWM), we established lipid-polymer hybrid nanoparticles (LPN) for loading ATX. The LPN enabled ATX to penetrate RWM and maintain concentrations in the perilymph in the inner ear for 24 h after a single injection. ATX-LPN were found to have favorable biocompatibility and to strongly affect cisplatin-induced generation of ROS, on the basis of DCFHDA staining in HEI-OC1 cells. JC-1 and MitoTracker Green staining suggested that ATX-LPN successfully reversed the decrease in mitochondrial membrane potential induced by cisplatin in vitro and rescued cells from early stages of apoptosis, as demonstrated by FACS stained with Annexin V-FITC/PI. Moreover, ATX-LPN successfully attenuated OHC losses in cultured organ of Corti and animal models (zebrafish and guinea pigs) in vivo. In investigating the protective mechanism of ATX-LPN, we found that ATX-LPN decreased the expression of pro-apoptotic proteins (caspase 3/9 and cytochrome-c) and increased expression of the anti-apoptotic protein Bcl-2. In addition, the activation of JNK induced by CDDP was up-regulated and then decreased after the administration of ATX-LPN, while P38 stayed unchanged. Conclusions:To best of our knowledge, this is first study concluded that ATX-LPN as a new therapeutic agent for the prevention of cisplatin-induced ototoxicity.

show abstract

Section: Discussionmentioning

confidence: 99%

Astaxanthin-loaded polymer-lipid hybrid nanoparticles (ATX-LPN): assessment of potential otoprotective effects

Chen

Tong

et al. 2020

J Nanobiotechnol

View full text Add to dashboard Cite

show abstract

“…It has been demonstrated that noise exposure, ototoxic drugs, and aging can lead to increased ROS generation [46][47][48][49][50][51][52][53]. On the molecular level, oxidative stress causes DNA damage and lipid peroxidation in the cochlea [54][55][56]. Targeted mutation of the gene for cellular glutathione peroxidase (Gpx1) increases susceptibility to noise-induced hearing loss in animal models [57].…”

Section: Discussionmentioning

confidence: 99%

Biocompatibility of Bone Marrow-Derived Mesenchymal Stem Cells in the Rat Inner Ear following Trans-Tympanic Administration

Eshraghi

Ocak

Zhu

et al. 2020

JCM

View full text Add to dashboard Cite

Recent advancements in stem cell therapy have led to an increased interest within the auditory community in exploring the potential of mesenchymal stem cells (MSCs) in the treatment of inner ear disorders. However, the biocompatibility of MSCs with the inner ear, especially when delivered non-surgically and in the immunocompetent cochlea, is not completely understood. In this study, we determined the effect of intratympanic administration of rodent bone marrow MSCs (BM-MSCs) on the inner ear in an immunocompetent rat model. The administration of MSCs did not lead to the generation of any oxidative stress in the rat inner ear. There was no significant production of proinflammatory cytokines, tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-6 and IL-12, due to BM-MSCs administration into the rat cochlea. BM-MSCs do not activate caspase 3 pathway, which plays a central role in sensory cell damage. Additionally, transferase dUTP nick end labeling (TUNEL) staining determined that there was no significant cell death associated with the administration of BM-MSCs. The results of the present study suggest that trans-tympanic administration of BM-MSCs does not result in oxidative stress or inflammatory response in the immunocompetent rat cochlea.

show abstract

“…Although systemic administration is an ideal drug delivery method for inner ear therapy, ATX and even ATX-LPN could not pass the BBB and BLB after IP injection with as high as 200 ug/ml ( Figure 1F). In the inner ear, many antioxidants, such as rosmarinic acid [28] , alpha-lipoic acid [29] , and Mitoquinone [30] have been applied to improve hearing loss after exposure to various damage, such as noise or ototoxic drugs. ATX, which has a stronger biological activity than other antioxidants because of its link with the cell membrane from the inside to the outside [31] , has been shown to protect against CDDP-induced nephrotoxicity in rats [32] and neomycin-induced ototoxicity in zebrafish hair cells [33] .…”

Section: Atx-lpn Partially Restored Cddp-induced Hearing Loss In Abr mentioning

confidence: 99%

“…The protective effect of ATX-LPN in terms of morphology was verified by rescuing OHCs in cultured cochlear explants. We then evaluated auditory function and found that hearing was restored by [20][21][22][23][24][25][26][27][28][29][30] dB SPL at a wide range of frequencies after ATX/ATX-LPN administration. Although greater CDDPinduced damage exists in the high-frequency area in both animals and humans [46] , a better restoration of hearing was observed.…”

Section: Atx-lpn Partially Restored Cddp-induced Hearing Loss In Abr mentioning

confidence: 99%

Astaxanthin-loaded polymer-lipid hybrid nanoparticles (ATX-LPN) Assessment of potential otoprotective effects

Chen

Tong

et al. 2020

Preprint

View full text Add to dashboard Cite

Background Ototoxicity is one of the major side effects of platinum-based chemotherapy, especially cisplatin therapy. To date, no FDA approved agents to alleviate or prevent this ototoxicity are available. However, ototoxicity is generally believed to be produced by excessive generation of reactive oxygen species (ROS) in the inner ear, thus leading to the development of various antioxidants, which act as otoprotective agents. Astaxanthin (ATX) is an interesting candidate in the development of new therapies for preventing and treating oxidative stress-related pathologies, owing to its unique antioxidant capacity. Methods and Results In this study, we aimed to evaluate the potential antioxidant properties of ATX in the inner ear by using the HEI-OC1 cell line, zebrafish, and guinea pigs. Because ATX has poor solubility and cannot pass through round window membranes (RWM), we established lipid-polymer hybrid nanoparticles (LPN) for loading ATX. The LPN enabled ATX to penetrate RWM and maintain concentrations in the perilymph in the inner ear for 24 h after a single injection. ATX-LPN were found to have favorable biocompatibility and to strongly affect cisplatin-induced generation of ROS, on the basis of DCFHDA staining in HEI-OC1 cells. JC-1 and MitoTracker Green staining suggested that ATX-LPN successfully reversed the decrease in mitochondrial membrane potential induced by cisplatin in vitro and rescued cells from early stages of apoptosis, as demonstrated by FACS stained with Annexin V-FITC/PI. Moreover, ATX-LPN successfully attenuated OHC losses in cultured organ of Corti and animal models (zebrafish and guinea pigs) in vivo. In investigating the protective mechanism of ATX-LPN, we found that ATX-LPN decreased the expression of pro-apoptotic proteins (caspase 3/9 and cytochrome-c) and increased expression of the anti-apoptotic protein Bcl-2. In addition, the activation of JNK induced by CDDP was up-regulated and then decreased after the administration of ATX-LPN, while P38 stayed unchanged. Conclusions To best of our knowledge, this is first study concluded that ATX-LPN as a new therapeutic agent for the prevention of cisplatin-induced ototoxicity.

show abstract

The Antioxidant Effect of Rosmarinic Acid by Different Delivery Routes in the Animal Model of Noise-Induced Hearing Loss

Abstract: The effectiveness of RA given via trans-tympanic injection could be interesting for the future application of this minimally-invasive procedure in the treatment of ROS-induced hearing loss.

Cited by 22 publications

References 36 publications

Astaxanthin-loaded polymer-lipid hybrid nanoparticles (ATX-LPN): assessment of potential otoprotective effects

Astaxanthin-loaded polymer-lipid hybrid nanoparticles (ATX-LPN): assessment of potential otoprotective effects

Biocompatibility of Bone Marrow-Derived Mesenchymal Stem Cells in the Rat Inner Ear following Trans-Tympanic Administration

Astaxanthin-loaded polymer-lipid hybrid nanoparticles (ATX-LPN) Assessment of potential otoprotective effects

Contact Info

Product

Resources

About