Plant-based therapies for gentamicin-induced ototoxicity: experimental evidence and pharmacological insightsAbstract
Gentamicin is an aminoglycoside antibiotic widely used in clinical practice, but its administration may lead to ototoxicity, resulting in cochlear and vestibular damage. Experimental studies have investigated the potential of medicinal plants and their bioactive compounds to prevent or mitigate this toxicity. This integrative review critically analyses preclinical evidence on the protective and therapeutic effects of medicinal plants and their derivatives in animal models of gentamicin-induced ototoxicity. Studies published between 1995 and 2025 were selected from the PubMed, Web of Science, and ScienceDirect databases. The main findings indicate that species such as Ginkgo biloba, Panax ginseng, Salvia miltiorrhiza, Nigella sativa, and Pyrola rotundifolia exert protective, preventive, and regenerative effects through antioxidant and anti-inflammatory mechanisms. These effects are mainly related to the reduction of oxidative stress, modulation of inflammation, and preservation of sensory cell integrity. The evidence supports the pharmacological potential of natural compounds for the prevention and treatment of ototoxicity.
Keywords:
gentamicin; ototoxicity; medicinal plants; animal models; oxidative stress
Resumo
A gentamicina é um antibiótico aminoglicosídeo amplamente utilizado na prática clínica, porém seu uso pode causar ototoxicidade, resultando em danos cocleares e vestibulares. Estudos experimentais têm investigado o potencial de plantas medicinais e seus compostos bioativos na prevenção ou mitigação desses efeitos tóxicos. Esta revisão integrativa analisa criticamente as evidências pré-clínicas sobre os efeitos protetores e terapêuticos de plantas medicinais e seus derivados em modelos animais de ototoxicidade induzida por gentamicina. Foram selecionados estudos publicados entre 1995 e 2025 nas bases de dados PubMed, Web of Science e ScienceDirect. Os principais resultados indicam que espécies como Ginkgo biloba, Panax ginseng, Salvia miltiorrhiza, Nigella sativa e Pyrola rotundifolia exercem efeitos protetores, preventivos e regenerativos por meio de mecanismos antioxidantes e anti-inflamatórios. Esses efeitos estão relacionados principalmente à redução do estresse oxidativo, modulação da inflamação e preservação da integridade das células sensoriais. As evidências reforçam o potencial farmacológico de compostos naturais para a prevenção e o tratamento da ototoxicidade.
Palavras-chave:
gentamicina; ototoxicidade; plantas medicinais; modelos animais; estresse oxidativo
1. Introduction
Medicinal plants and their phytocompounds have attracted increasing interest due to their therapeutic potential, widely associated with antioxidant, anti-inflammatory, and cytoprotective properties. These mechanisms are particularly relevant in clinical conditions characterized by oxidative stress and cellular apoptosis, such as drug-induced ototoxicity (Ansari et al., 2025; Riaz et al., 2023).
Ototoxicity is defined as functional and structural alterations in the auditory and/or vestibular systems resulting from exposure to chemical agents, which can lead to irreversible manifestations such as hearing loss, tinnitus, and vertigo (Greguske et al., 2021; Sedó-Cabezón et al., 2014). Among the most well-known ototoxic agents are aminoglycoside antibiotics, whose use revolutionized the treatment of severe infections but brought significant adverse effects. Historically, concerns arose from the use of streptomycin and dihydrostreptomycin in tuberculosis treatment, when the first reports of drug-induced hearing loss were described (Guthrie, 2008; Schacht, 1998).
Currently, gentamicin (GM) is one of the most widely used aminoglycosides, especially in the treatment of Gram-negative bacterial infections (Tian et al., 2013). Despite its efficacy, prolonged use is associated with important adverse effects, including nephrotoxicity and ototoxicity, the latter characterized by hearing loss, tinnitus, and, in some cases, vertigo due to vestibular impairment (Yang et al., 2011). These manifestations are related to the selective destruction of sensory hair cells (HCs) and inner ear neurons (Ruan et al., 2014a). Initially, GM predominantly affects outer hair cells (OHCs) in the basal turn of the cochlea; at higher doses, it also damages inner hair cells (IHCs), and nerve fibers can be injured independently of HC status (Ruan et al., 2014a; Somdaş et al., 2015).
Aminoglycoside-induced ototoxicity involves complex mechanisms, including mitochondrial oxidative stress, activation of pro-inflammatory pathways, and caspase-3-mediated apoptosis (Hong et al., 2025; Kim et al., 2023). Substances capable of neutralizing reactive oxygen species (ROS) or stimulating endogenous antioxidant systems represent promising candidates for preventing or treating this adverse effect.
Given the absence of specific pharmacological therapies to mitigate ototoxic damage, alternative strategies have been investigated, including the use of natural compounds. Several medicinal plants and their derivatives have demonstrated efficacy in modulating oxidative stress and protecting hair cells in experimental models. Notably, some of these species have a traditional use history in communities for treating auditory disorders or inflammation, strengthening the ethnopharmacological relevance of their investigation.
Therefore, understanding the efficacy of these phytotherapeutics and their mechanisms of action is essential for developing safe and effective approaches. This integrative review aims to critically analyze the available evidence on the effects of medicinal plants and their derivatives in animal models of gentamicin-induced ototoxicity, highlighting the main compounds, their preventive, protective, and regenerative mechanisms, and gaps for future research.
2. Materials and Methods
2.1. Search strategy
An integrative review was conducted through a comprehensive search of the scientific literature using electronic databases, including PubMed, Web of Science, ScienceDirect, Scopus, and Springer, considering publications up to August 2025. Given the specificity of the topic and the limited number of records with uniform descriptors, varied search strategies were applied, combining controlled descriptors (MeSH/DeCS) and free keywords. The literature search was performed using different terms, including “medicinal plants”, “phytotherapy”, “ototoxicity”, “animal model”, “experimental models”, “gentamicin”, “aminoglycosides”, “vestibulotoxicity”, and “vestibular dysfunction”, among others.
After applying the inclusion and exclusion criteria, 27 articles were selected that met the objectives of this review (Figure 1).
2.2. Eligibility criteria and study selection
This integrative review followed systematized procedures to ensure transparency in the selection and analysis of the included studies. Inclusion and exclusion criteria were defined based on the scope and objectives of the present review.
Studies were included if they simultaneously met the following criteria: experimental investigations using animal models (in vivo) exposed to gentamicin; interventions with medicinal plants, plant extracts, or natural compounds; and evaluation of ototoxicity and vestibular dysfunction through behavioral, histological, functional, or electrophysiological tests (Table 1).
Medicinal plants and phytochemicals tested against gentamicin-induced ototoxicity in experimental animal models.
Exclusion criteria were: studies involving human subjects, in vitro models, or literature reviews; studies in which the tested treatment did not involve plants, phytocompounds, or natural derivatives; and studies with incomplete or duplicate data or methodologies that did not allow the extraction of relevant information for this review.
3. Results
A total of 27 studies on the use of medicinal plants or plant-derived compounds in gentamicin (GM) induced ototoxicity in animal models were identified. Of these, 8 studies addressed vestibulotoxicity, with emphasis on vestibular dysfunction, and 19 studies investigated cochleotoxicity. The publications spanned the period from 1995 to 2025.
Rodents were the most frequently used models, with a predominance of Sprague-Dawley rats, generally exposed to GM via intraperitoneal (IP) administration at doses ranging from 100 to 160 mg/kg for 10 to 15 days. To a lesser extent, studies employed Wistar rats under similar protocols, as well as BALB/c or C57BL/6J mice, using higher doses (100–400 mg/kg). Models using guinea pigs were also reported, varying in route of administration (IM, IP, or IT) and duration (1 to 14 days).
This variability in species, doses, and administration routes reflects differences in experimental objectives and model sensitivity, which limits direct comparison across studies.
The included studies employed different approaches to assess gentamicin-induced ototoxicity and vestibular function. Vestibular function was investigated through behavioral and motor reflex tests, such as Rotarod, tail suspension, swimming, and balance tests, among others, which allowed the identification of alterations in postural control and motor coordination.
Auditory function and cochlear alterations were examined using electrophysiological and morphological methods, including electrocochleography, auditory brainstem responses, otoacoustic emissions, and histological analyses by electron or confocal microscopy. In addition, immunohistochemical and molecular techniques were employed to investigate apoptosis and the integrity of hair cells.
Overall, the studies combined behavioral tests, electrophysiological analyses, and histopathological approaches, providing a comprehensive characterization of gentamicin-induced vestibular and auditory dysfunctions across different animal models.
Several medicinal plants and natural compounds have demonstrated protective, preventive, and regenerative effects against gentamicin-induced ototoxicity. Among the most extensively investigated agents are Ginkgo biloba, Panax ginseng, Curcuma longa, and Nigella sativa, whose extracts or active constituents exhibited antioxidant, anti-inflammatory, and neuroprotective properties capable of preserving hair cell integrity and improving vestibulocochlear function.
Some studies also reported regenerative effects, particularly with compounds such as quercetin, naringenin, and rutin, which promoted tissue repair and reduced apoptosis. Taken together, the evidence indicates that different phytochemicals — including flavonoids, polyphenols, and antioxidant vitamins — exert significant benefits in preventing and mitigating gentamicin-induced damage.
Table 2 summarizes the plants, bioactive compounds, and main effects observed in the evaluated experimental models.
Summary of the effects of medicinal plants and natural compounds on protection, prevention, and regeneration of gentamicin-induced ototoxicity
4. Discussion
4.1. Experimental models
The reviewed studies employed different experimental models, with variations in species, strain, sex, and age of the animals. These differences influence sensitivity to gentamicin (GM) and require dose adjustments to achieve consistent induction of ototoxicity, since doses effective in rats do not always produce the same effect in mice or guinea pigs (L. Chen et al., 2012; Sinswat et al., 2000). Moreover, the pharmacokinetics of GM in the inner ear vary according to species and experimental conditions, which affects the dose required to induce ototoxic injury (Blunston et al., 2015; Federspil et al., 1976).
As observed in the results, Sprague-Dawley rats were the most commonly used model, generally subjected to intraperitoneal (IP) administration of 100 to 120 mg/kg for 10 to 15 days. This dosage range is widely recognized as effective for inducing ototoxicity, as demonstrated in comparative studies (Somdaş et al., 2015; Blunston et al., 2015; Talaat et al., 2025). Thus, these protocols represent a robust experimental model for testing agents with therapeutic potential.
Despite the predominance of male rats, some studies included females, although no controlled comparisons between sexes have been reported (Koçak et al., 2017; Tuna and Tüzemen, 2023, 2024; Sagit et al., 2015; Tian et al., 2013). This methodological gap, combined with the lack of standardization in doses and routes of administration, underscores the need for more consistent protocols to improve the reproducibility and translational applicability of the findings.
The Wistar strain generally follows the same dosage pattern adopted for Sprague-Dawley rats, although variations in exposure time are observed (Uzun et al., 2012, 2016), Salcan et al., 2021). This flexibility reflects differences in experimental objectives. For example, Aydemir et al. (2022) administered 120 mg/kg of GM intraperitoneally (IP) for 14 days to evaluate the protective effect of caffeic acid phenethyl ester (CAPE), while Aydin et al. (2012) applied the same dose for 7 days and also achieved successful induction of ototoxicity. In contrast, Lopez-Gonzalez et al. (2000) used 160 mg/kg via intramuscular injection for 7 days, reinforcing the variability among protocols.
In addition, the intratympanic (IT) route was widely employed, particularly in studies focused on evaluating vestibular dysfunctions (Erkoç et al., 2023; Güneri et al., 2017; Vural et al., 2017).
Although this review identified few studies using plants and their derivatives in mice, these animals are widely used in research involving gene therapies and ototoxic agents, showing heterogeneity in routes of administration, dosages, and experimental models (Hui et al., 2022; Li et al., 2016; Pfannenstiel et al., 2009) . Examples include the BALB/c model, treated with 100 mg/kg for nine days (Kaplan et al., 2017), and the C57BL/6J model, subjected to 200 mg/kg for seven days (Niu et al., 2021) or 400 mg/kg for 14 days (Jiang et al., 2024).
It is observed that higher doses of GM are required to induce vestibular dysfunction in mice, as vestibular cells exhibit greater resistance to the antibiotic, accumulate lower amounts of the drug, and require stronger activation of toxic pathways to produce functional impairment. This behavior contrasts with the higher sensitivity of cochlear cells, which sustain damage even at lower doses (Kinoshita et al., 2023; Liu et al., 2015; Sultemeier and Hoffman, 2017).
Guinea pigs were the models that showed the greatest variation in administration route, dose, and exposure time. Several studies standardized the use of GM to induce ototoxicity in this model, reporting consistent outcomes such as significant hearing loss and cochlear hair cell damage. Among the routes evaluated, the most frequently used were intramuscular (IM) and intraperitoneal (IP), generally with lower doses than those employed in rats and mice, averaging 100 mg/kg (Fetoni et al., 2003, 2004; Long et al., 2004; Shi et al., 2014), administered for periods of 10 to 14 days. In one of the analyzed studies, a dose of 160 mg/kg via IM was administered for 10 days (Xuan et al., 1995). Higher doses, such as 160 mg/kg/day for 7 days, accelerate hearing loss but are not required to ensure consistent induction of ototoxicity (Turan et al., 2017). Thus, the data indicate that a dose of 100 mg/kg is sufficient to induce robust and reproducible ototoxicity in guinea pigs.
The lack of uniformity in gentamicin doses across studies represents a significant challenge for comparing results. While some protocols used lower doses for shorter periods, others employed higher and more prolonged administrations, reflecting different experimental objectives. This variation can directly affect the magnitude of vestibular or cochlear injury, as well as the observed efficacy of the tested compounds. Thus, the absence of standardization hinders the establishment of comparable parameters and highlights the need to define more consistent dose ranges in future experimental models of ototoxicity.
Some selected studies also employed the intratympanic (IT) route to induce ototoxicity (Jung et al., 1998; Kinoshita et al., 2023). This approach stands out as a relevant alternative for experimental models, as it allows detailed investigation of the cellular and molecular mechanisms involved in ototoxicity, including the production of reactive oxygen species, apoptosis, and enzymatic alterations (Heinrich et al., 2006; Takumida et al., 1999). Moreover, it enables the analysis of gentamicin accumulation patterns in different cochlear and vestibular cell types, revealing differences in susceptibility and intracellular transport (Heinrich et al., 2015). Another important aspect is that local application provides greater reproducibility and control over the dose effectively delivered to the inner ear, facilitating comparisons across studies (Hibi et al., 2001).
Differences among experimental models and dosing protocols also influence the interpretation of the protective effects of the studied compounds. Animals of different strains or ages may respond differently to the same ototoxic agent, altering the magnitude of the observed effect (Chen, 2019; Jodynis-liebert & Kujawska, 2020). Likewise, variations in dose, timing of inoculation, or duration of exposure to the tested compounds may determine whether the observed effect is predominantly protective, preventive, or regenerative (Calabrese, 2016; Chesler et al., 2022). These factors underscore the need to carefully consider experimental conditions when comparing results across studies and suggest that fine-tuning of dose and model is essential to optimize therapeutic efficacy in future research on ototoxicity (Jiang et al., 2024; Maroto et al., 2021).
The assessment of vestibular function is still scarcely and inconsistently explored. Among the included studies, nine employed behavioral tests - such as observation of posture, balance, gait, and reflexes (e.g., the righting reflex) - to detect vestibular dysfunction in a sensitive and noninvasive manner (Abd-Elhakim et al., 2021, 2022; Choung et al., 2011; Fetoni et al., 2003; Jiang et al., 2024; Kaplan et al., 2017; Kinoshita et al., 2023; Tian et al., 2013; Uzun et al., 2016). Although useful, results may vary depending on the evaluator’s training, strain, and experimental conditions (Fetoni et al., 2003; Jiang et al., 2024).
Gentamicin induces progressive vestibular injury through the destruction of sensory hair cells, resulting in stable deficits in balance and postural reflexes, which can be measured using balance, righting, and swimming tests (Maroto et al., 2021; Jiang et al., 2024).
Behavioral tests have demonstrated sensitivity in detecting vestibular deficits and, when combined with morphological analyses, provide a robust functional assessment. However, methodological heterogeneity — including test selection, scoring criteria, and experimental conditions — limits direct comparability across studies (Abd-Elhakim et al., 2021, 2022; Choung et al., 2011; Jiang et al., 2024; Kaplan et al., 2017; Kinoshita et al., 2023; Tian et al., 2013).
Tests such as Rotarod, swimming, head tilt, and tail suspension are widely employed with semi-quantitative scoring scales, whereas specific procedures (e.g., the caloric test) enable evaluation of the vestibulo-ocular reflex (Kinoshita et al., 2023; Güneri et al., 2017; Hui et al., 2022).
Complementarily, studies have integrated electrophysiological, histological, and biochemical techniques (ECochG, SEM, immunohistochemistry, oxidative markers), which allow for the correlation of structural alterations with functional deficits and a deeper understanding of the mechanisms of action of the tested compounds (Fetoni et al., 2004; Tian et al., 2014; Edizer et al., 2017).
4.2. Effects of medicinal plants and phytocompounds in experimental models
Medicinal plants and their derivatives have shown consistent protective effects against gentamicin-induced ototoxicity, acting both preventively and reparatively. In different experimental models, these compounds reduced the severity of lesions and promoted functional and structural recovery of the vestibular system (Kinoshita et al., 2023; Salcan et al., 2021). The main benefits observed include improvements in balance and motor coordination, as well as partial preservation or regeneration of the sensory cells within the labyrinth.
The underlying mechanisms are mainly related to the modulation of oxidative stress and inflammation, involving the neutralization of reactive oxygen species, stimulation of endogenous antioxidant defenses, and inhibition of apoptotic and necrotic pathways (Abd-Elhakim et al., 2022; Haryuna et al., 2021). Some compounds also exhibit regenerative effects on cochlear and vestibular structures, further reinforcing their therapeutic potential (Choung et al., 2011; Jiang et al., 2024; Sagit et al., 2014). Altogether, these findings support the role of such substances as promising pharmacological candidates for the prevention and recovery of vestibular dysfunctions associated with ototoxicity.
4.2.1. Plants and compounds with protective effects
Experimental studies have identified several plant species and natural compounds with potential protective effects against gentamicin (GM)-induced ototoxicity. Among them, Pyrola rotundifolia L. and Astragalus membranaceus (Xuan et al., 1995), Ginkgo biloba (Jung et al., 1998), and red ginseng (Panax ginseng), whose active component ginsenoside Rb1 demonstrated both cellular and behavioral protection by preventing hair cell loss and preserving vestibular function after GM exposure (Choung et al., 2011; Tian et al., 2013) stand out. Other relevant compounds include puerarin, derived from Pueraria phaseoloides (Niu et al., 2021), curcumin, the main polyphenol of turmeric (Abd-Elhakim et al., 2021, 2022), and alpha-tocopherol (vitamin E), which also showed protective effects (Fetoni et al., 2003).
Most of these agents share antioxidant and anti-inflammatory mechanisms. They reduce oxidative stress by decreasing the production of reactive oxygen species (ROS), the main mediators of cellular damage (Shi et al., 2014; H. Yang et al., 2024; Zhang et al., 2024). In addition, many compounds modulate proteins involved in apoptosis, reducing the activation of caspase-3, BAX, and p53, while increasing the expression of anti-apoptotic proteins such as BCL-2, thereby protecting auditory and vestibular cells (Hong et al., 2025; Kim et al., 2023; Niu et al., 2021). Some also act on the regulation of intracellular signaling pathways associated with cell survival and tissue regeneration (Hong et al., 2025; Niu et al., 2021; Yang et al., 2011; Zhang et al., 2024). These protective effects, demonstrated by behavioral and histological studies, indicate a promising potential for preventive and therapeutic strategies against GM-induced ototoxicity.
4.2.2. Plants and compounds with preventive effects
Plants and compounds that demonstrated preventive effects against gentamicin (GM)-induced ototoxicity mainly include species with recognized antioxidant and neuroprotective activity. Among them, Drynaria fortunei (Kunze) stands out, evaluated for its potential to reduce oxidative stress and preserve cells (Long et al., 2004). Ginkgo biloba also showed consistent results in attenuating vestibular damage, attributed to its sensory antioxidant and anti-inflammatory activity (Yang et al., 2011). Nigella sativa proved promising in studies using both the whole extract (Edizer et al., 2017; Tuna and Tüzemen, 2023, 2024) and its main bioactive component, thymoquinone (Sagit et al., 2014), showing protective effects on sensory cells and vestibular structures. Another relevant phytocompound is gastrodin, derived from Gastrodia elata, recently associated with the modulation of antioxidant and anti-apoptotic pathways, demonstrating preventive potential against vestibular damage as assessed by behavioral tests (Jiang et al., 2024).
In addition to plants, isolated bioactive compounds such as alpha-linolenic acid have shown promising results in preventing ototoxicity by inhibiting apoptosis and inflammation (Kaplan et al., 2017). Alpha-tocopherol (vitamin E) has also demonstrated preventive efficacy (Fetoni et al., 2004), reinforcing the role of redox balance in protection against ototoxic injury.
4.2.3. Plants and compounds with regenerative or curative effects
Among the substances evaluated, some demonstrated regenerative or curative effects against gentamicin-induced damage. Notable examples include Drynaria fortunei (Kunze) (Kunze) (Long et al., 2004) , Ginkgo biloba (Yang et al., 2011), Salvia miltiorrhiza (Shi et al., 2014) and garlic (Allium sativum) (Uzun et al., 2012, 2016). In addition, several flavonoids, such as quercetin (Sagit et al., 2015), naringenin (Koçak et al., 2017), rutin (Salcan et al., 2021) and 7,8-dihydroxyflavone (Kinoshita et al., 2023) also showed potential to promote tissue regeneration and reversal of vestibular damage.
The flavonoid 7,8-dihydroxyflavone, a TrkB agonist, was shown to promote hair cell regeneration, preservation of the vestibular nerve, and synaptic remodeling, resulting in recovery of vestibular function after GM treatment (Kinoshita et al., 2023). The proposed mechanisms include antioxidant action, modulation of apoptotic and inflammatory pathways, and stimulation of survival and regeneration of sensory cells in the inner ear.
4.2.4. Underlying mechanisms and multifunctional properties
In experimental models, plant-derived compounds preserved cellular integrity and improved performance in balance and coordination tests, indicating consistent functional effects. Some exhibited multifunctional properties, with simultaneous preventive and regenerative actions (Long et al., 2004; Yang et al., 2011), reinforcing their therapeutic potential against gentamicin (GM)-induced ototoxicity.
The curative and regenerative effects observed after GM exposure mainly involve the restoration of cellular functions, inhibition of apoptosis, and modulation of antioxidant pathways (Choung et al., 2011; Jiang et al., 2024; Sagit et al., 2014), The mechanisms of action include direct neutralization of reactive oxygen species, stimulation of endogenous defenses (such as antioxidant enzymes and cell survival factors), and modulation of inflammatory and apoptotic pathways, all of which contribute to the preservation of auditory and vestibular functions.
Despite these promising findings, important limitations remain. Most experimental studies continue to focus primarily on nephrotoxicity, whereas ototoxicity - and particularly vestibular dysfunction - has been comparatively underexplored. In addition, heterogeneity in experimental models, outcome measures, and treatment protocols hampers direct comparisons across studies and limits clinical extrapolation.
An important source of variability among the studies analyzed in this review concerns the extraction methods used to obtain plant-derived compounds. Different extraction approaches, such as aqueous and ethanolic methods, may substantially influence the concentration, stability, and bioavailability of active metabolites, including flavonoids and polyphenols such as quercetin and curcumin. Experimental studies in rodent models have demonstrated that extraction protocols directly affect the chemical profile and biological activity of plant extracts, which may impact the interpretation of effective doses and protective outcomes (Bati et al., 2023; Macorini et al., 2022; Marinho et al., 2022). These findings underscore the need for caution when comparing results derived from different extraction procedures and distinct phytochemical compositions.
In this context, although in vivo experimental models are widely employed to investigate the cellular and molecular effects of bioactive substances under conditions of chemically induced toxicity, most studies rely on the direct administration of these compounds in animal models. This approach does not fully account for pharmacokinetic challenges in humans, particularly those related to bioavailability and penetration across the blood–labyrinth barrier (Bomfim et al., 2022). Furthermore, variability in gentamicin dosing protocols - ranging from 100 to 160 mg/kg - is known to influence the severity of ototoxic injury and may affect the magnitude of the protective effects attributed to plant-based therapies (Ruan et al., 2014b; Sedó-Cabezón et al., 2014; Somdaş et al., 2015). Collectively, these factors highlight the need for standardized experimental protocols, careful consideration of extraction methodologies, and pharmacokinetic-oriented approaches to enhance the translational relevance and therapeutic potential of plant-derived compounds in the prevention and treatment of aminoglycoside-induced ototoxicity.
5. Conclusion
The reviewed studies demonstrate that medicinal plants and their derivatives exert protective (e.g., Pyrola rotundifolia L., Astragalus membranaceus, Ginkgo biloba, Panax ginseng), preventive (Drynaria fortunei, Nigella sativa), and regenerative (Salvia miltiorrhiza, Allium sativum) effects in experimental models of ototoxicity. These actions are primarily associated with the modulation of oxidative stress, attenuation of inflammation, and preservation of the structural integrity of sensory cells within the inner ear. Despite the heterogeneity among gentamicin-induced ototoxicity models and administration protocols, the findings collectively reinforce the therapeutic potential of these agents and underscore the need for future studies to standardize experimental designs and further elucidate their mechanisms of action, paving the way for safe and effective clinical applications.
Acknowledgements
The first author thanks the Coordination for the Improvement of Higher Education Personnel – Brazil (CAPES) for supporting her through a doctoral fellowship in the Graduate Program in Health and Development in the Central-West Region at the Federal University of Mato Grosso do Sul. We also extend our gratitude to the National Council for Scientific and Technological Development (CNPq) and the Financing Agency for Studies and Projects (FINEP).
Data Availability Statement
No new data were generated or analyzed in this study.
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