Discussion
Otomycosis refers to fungal infections of the external ear, including
the auricle, auditory canal, eardrum, and middle ear. The symptoms
include otorrhea, otalgia, itchiness, and it is usually a recurrent
disease [12, 13]. Fortunately, this entity is not life-threatening,
and complications are uncommon except in immunocompromised patients as
it is an opportunistic infection. However, this disease presents
difficulties for the otolaryngologist and the patient, as it has a high
recurrence rate and residual disease. Additionally, it necessitates
long-term treatment and monitoring [13]. The mainstay of treatment
for otomycosis is thorough removal and cleaning of the infected area
with topical antifungal ear drops [14]. Topical medications are
preferable to systemic medications because they have a low risk of
systemic side effects and a high concentration in the targeted infected
area.
Aspergillus and Candida are the most prevalent fungal
species isolated in otomycosis [13]. There has been a report of
growing resistance to classical antifungal agents that contain azoles,
polyenes, and echinocandin, which are usually effective againstAspergillus and Candida [15]. This is described as
clinical resistance, which is the inability to eliminate a fungal
infection despite the antifungal agents having in vitro action against
the pathogen [15]. Currently, there is no FDA-approved antifungal
otic solution for otomycosis treatment [16]. Physicians have
struggled to discover the most efficient antimycotic medication to treat
this ailment since there are numerous medicines available with varying
antimycotic properties. This opens up the research of using herbal
plants as an alternative drug to treat otomycosis.
According to the World Health Organization, herbal plants are one of
the ideal sources for obtaining a range of medicines [17]. Hence,
these plants should be studied further to evaluate their
benefits, safety, and effectiveness. Henna leaf (Lawsonia inermis) has
long been valued for its healing and medicinal properties since ancient
times. The therapeutic effects of various components of Henna are due
to its biologically active compound of 2-hydroxynapthoquinone (Lawsone)
[3]. Studies have shown that henna leaf extracts in Malaysia inhibit
the development of pathogenic fungi [4]. Although commonly used as a
natural remedy to treat skin, outer ear, and hair lesions, the safety
status and possible ototoxic effects of henna leaves are still to be
reported. Ototoxicity is identified as functional disability and
cellular degradation of the inner hair cells by therapeutic drugs and
chemical compounds and is categorized into cochleotoxicity and
vestibulotoxicity [18].
Two Malaysian henna extracts were used, which are aqueous extract and
ethanol extract, which, their fungitoxic activity has been established
[4]. Yaroko et al. tested the antifungal activity of Malaysian henna
leaf extract against two prevalent otomycotic pathogenic fungi, which
were Aspergillus niger and Candida albicans . He discovered
that the aqueous extract of Malaysian Henna is superior in inhibiting
the growth of A. niger . In contrast, ethanol extract is more
effective in suppressing the growth of C. Albicans [4]. Three
concentrations of aqueous and ethanol henna extracts were used in this
study; 25mg/ml, 50mg/ml, and 75mg/ml. Statistical analysis revealed
significant inhibition of A. niger with aqueous extract
concentrations of 75mg/ml and 50mg/ml, while ethanol extract was
significant with a concentration of 75mg/ml only. Meanwhile, henna
ethanol extract demonstrated near-significant inhibition againstC. Albicans with a 75mg/ml concentration. The least inhibition
was recorded with a 25mg/ml concentration for both extracts [4].
However, to ensure that the substance is administered into the ear canal
and absorbed by the inner ear and middle ear mucosa, aqueous and ethanol
henna at a concentration of 25% were used and instilled
transtympanically [4]. Nadjib et al. also studied using the same
concentration of 25% by mixing 25g of powdered henna plant with 100 ml
of different solvents to test against C.albicans and various
microbes [9]. Meanwhile, Zakaria et al. recommended 20mg/ml as the
best concentration to inhibit many pathogenic fungi in aqueous or
ethanol extract [19]. This concentration has been shown to have a
sufficient antifungal effect in a thin diluted solution. It is suitable
for physicians and patients to administer in the form of an ear drop.
Wistar rats are widely used in otological studies and were chosen in our
study [20, 21]. The middle and inner ear anatomy is nearly identical
to humans. The rat cochlear comprises two and a half turns, making it a
good model for cochleotoxicity and vestibulotoxicity research [22].
The rats were all three months old when used in the experiment,
equivalent to a 20-26-year-old human [23]. This is due to the
widespread recognition of the age connection between mice and humans,
particularly regarding neurological development.
The four established vestibular parameters observed in rats after
transtympanic instillation of ototoxic agents were dyskinetic head
movements and circling, tail hanging, air righting reflex, and contact
inhibition of righting reflex [11]. A normal baseline vestibular
parameters were ensured in all rats following the inclusion criteria.
The henna extract was injected into the right middle ear of each rat for
constant observational behaviour. Vestibular parameters were recorded at
four hours, twenty-four hours, seventy-two hours, one week, two weeks,
and three weeks after transtympanic instillation. Acute vestibular
changes can be observed in rats as early as 4 hours and as late as three
weeks after transtympanic instillation. This is because rats can
reestablish normal postural locomotor function following a temporary
vestibular insult on one side [23]. The findings recorded by blinded
observers were zero or normal responses in all rats at every vestibular
interval tested. Hence, statistical analysis could not be implemented in
this study.
To conclude, henna extract in aqueous and ethanol extract can safely be
used in otomycosis without vestibulotoxic effect in an animal model,
even with a tympanic membrane perforation. Malaysian Henna showed
potential to be used as an alternative topical antifungal eardrop in
treating otomycosis. We recommend conducting a histological study of the
cochlear in an animal model to assess the effect on inner hair cells to
fully establish the safety efficacy of Henna before human clinical
trials.