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Hair loss and regeneration performed on animal models



Research in the field of reversal hair loss remains a challenging subject. As Minoxidil 2% or 5% and Finasteride are so far the only FDA approved topical treatments for inducing hair regrowth, research is necessary in order to improve therapeutical approach in alopecia. In vitro studies have focused on cultures of a cell type - dermal papilla or organ culture of isolated cell follicles. In vivo research on this topic was performed on mice, rats, hamsters, rabbits, sheep and monkeys, taking into consideration the advantages and disadvantages of each animal model and the depilation options. Further studies are required not only to compare the efficiency of different therapies but more importantly to establish their long term safety.
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1Department of Physiopathology, Iuliu Hatieganu University of Medicine and
Pharmacy, Cluj-Napoca, Romania
2Department of Physiology, Iuliu Hatieganu University of Medicine and Pharmacy,
Cluj-Napoca, Romania
3Department of Histology, Iuliu Hatieganu University of Medicine and Pharmacy,
Cluj-Napoca, Romania
Research in the eld of reversal hair loss remains a challenging subject.
As Minoxidil 2% or 5% and Finasteride are so far the only FDA approved topical
treatments for inducing hair regrowth, research is necessary in order to improve
therapeutical approach in alopecia. In vitro studies have focused on cultures of a cell
type - dermal papilla or organ culture of isolated cell follicles. In vivo research on
this topic was performed on mice, rats, hamsters, rabbits, sheep and monkeys, taking
into consideration the advantages and disadvantages of each animal model and the
depilation options. Further studies are required not only to compare the efciency of
different therapies but more importantly to establish their long term safety.
Keywords: hair regrowth, animal models, research in vivo, alopecia
for signaling or communication and sometimes provides
defensive functions [11].
Hair can also modify its color over the time, both in
animals and humans: from vellus hairs in babies (uncolored,
soft hair) into nal hair in adult males (colored beard, thick
and strong hair) [12]. Along the aging process it loses its
pigment and becomes white.
Although human hair has lost its main
thermoregulatory function, hair growing on the head has an
important role in heat insulation and cooling by evaporating
sweat from soaked hair [13,14]. It also protects the scalp
against ultra-violet radiation by acting like a sunscreen
Structure of hair
Hair is deriving from the ectoderm of the skin and
represents an accessory structure of the integument along
with the sebaceous glands, sweat glands and nails [8,12].
The word “hair” usually refers to two distinct structures:
the hair follicle (beneath the skin) and the shaft of the
hair (hard lamentous part that extends above the skin
surface). In a cross section evaluation the shaft consists of
The physical appearance of both males and females
is under society pressure, due to the interest in the general
aspect of the individual regarding body shape, hair, make-
up and clothing [1-5].
Hair brings an important contribution to the outlook
of human body [6,7] playing an interesting part in social and
sexual communication, as many hair loss studies show [8]
This idea is also supported by the fact in some
cultures young women are asked to cover their hair,
which indirectly suggests its role in the overall beauty and
Functions of hair
Hair represents a dening characteristic of
mammals, with an important thermoregulatory function.
Also it has camouage purposes, hair follicles being able
to modify their type and density during seasonal coat
changes [9]. Besides offering protection, hair also has a
sensory function, extending the sense of touch that occurs
at skin level [10]. In animals, the hair/fur is often used
DOI: 10.15386/cjmed-583
Manuscript received: 21.09.2015
Accepted: 05.10.2015
Address for correspondence:
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three layers, starting from the outside: the cuticle (having
several layers of at, thin cells, overlapping one another),
the cortex (containing the keratin bundles in rod-like cell
structures) and the medulla (a disorganized and open area
at the ber’s center) [17,18].
On the other hand, in the dermis, we nd the bulb,
which maintains stem cells that not only re-grow the hair
after it falls out, but are also recruited to repair skin after a
wound [9].
The hair follicle pigmentary unit provides the hair
shaft melanin components, due to precise interactions
between follicular melanocytes, keratinocytes and
specialized dermal papilla broblasts (also involved
in wound healing) [19,20]. The dermal papilla has an
important role in hair formation, growth and cycling [21].
The blood vessels from the dermal papillae nourish all hair
follicles and offer nutrients and oxygen to epidermal cells
in the lower layers.
In the human skin, the dermal papillae are small
extensions of the dermis into the epidermis and at the
surface of the hands and feet, they appear as epidermal or
papillary ridges, also called ngerprints [22].
Biology of the hair loss and hair regrowth
Human hair is different from hair grown by
mammals, due to the unsynchronized growth cycles. Even
if there is a certain seasonal co-ordination, each human
hair follicle works independently [23,24,25]. This mosaic
human pattern consists of hair in different stages: 90%
anagen (growth phase), 1-2% catagen (regression phase)
and 8-9% telogen (resting phase). [26,27]. The cyclic
changes from anagen to telogen via catagen involve rapid
remodelling of both the epithelial and dermal components
of hair follicles [28,29]. In animals, as in humans, the hair
cycle is inuenced by stimulatory and inhibitory factors,
such as hormones, growth factors, cytokines, neuropeptides
and pharmaceutical products [26,30,31].
The dermal papilla, as the main mesenchymal
component, induces the new hair follicles formation and
maintains hair growth [32]. In telogen phase the old hair
is lost, but the follicle will be regenerated in early anagen,
when a new hair grows up. In order for this to happen, the
dermal papilla cells support an increased cell division and
growth rate that also require a good supply of nutrients and
a toxin-free environment for the growing cells. If these
requirements are not fullled the follicles will remain in
the telogen phase [33].
Two factors usually determine terminal hair
miniaturization leading to hair loss. The rst is the
shortening of the anagen, within an abnormal hair cycle
and the anagen: telogen rate shifting from 6:1 to 2:1. The
consequence of this process would be a shortening of hairs,
shaft loss and an increased number of hairs in telogen phase.
The second factor with a negative impact on hair growth is
the small size dermal papilla or the hair matrix leading
to hair modication both in diameter and aspect. Final hair
(thick and pigmented) turns into vellus (thin and white).
Scientists have also discovered that in hair loss, the scalp
suffers of vasoconstriction and hypoxia [34,35,36].
The sensitive response to androgen is the second
feature characterizing human hair in contrast to the hair
grown by mammals. An excess of androgens generates hair
miniaturization and thinning, followed by hair fall and loss
of pigment, mostly in the vertex and the crown-frontal area
of the scalp [37,38].
There are some characteristics of the hair depending
on localization in a specic site of the body: beard, axially
and pubic hair react differently than hair from the scalp,
as they are androgen-sensitive [12]. The metabolization of
the testosterone into 5-alpha-dihydrotestosterone has also
been of great research interest. Results show that good
metabolization limits the length of hair growth (beard) and
the 5 alpha-reductase deciency produces strong thick hair
(axilla and pubic area) [27,39,40,41,42].
On the other hand, androgens act on the hair via the
dermal papilla and stimulate the production of terminal hairs
after puberty, but have no hair growth effect on eyelashes
and the occipital area [43,44]. Androgens seem to alter the
production of regulatory factors (soluble paracrine factors
and extracellular matrix components) by the dermal papilla
cells [21].
Consequences of hair loss
Although a natural part of the aging process, hair
loss represents a great concern for the patient, who suffers
from anxiety and distress more severely than expected
[45]. Several studies already showed that this common
dermatological condition generates adverse psychosocial
sequelae [46]. Cash et al found that the psychological
effects of hair loss on women are far more severe than
in male subjects. Surveys have shown that around 40%
of women with alopecia have had marital problems and
around 63% claimed to have career related problems [47].
Hair loss is a stressful experience for both sexes, but
substantially more distressing for women, as they do not
accept the disease, neither do they cope with it as easily as
men [48]. Stress functions as a cause and risk factor in the
development of the disease, but it is also a consequence
of hair loss. Alopecia determines a poor quality of life by
the physical, psychological and social consequences it
produces. It causes low self-esteem, depression and distorts
social perception and psychosocial functioning [49,50].
A large variety of over the counter products claim
to treat hair loss pathology. This multibillion dollar,
worldwide market of hair tonics, hair balms, hair masks,
shampoos, leave in conditioners, topical solutions or foams
function as potential anti-hair loss agents [51]. However, in
most of the cases, clinical studies do not prove how these
doubtful hair growth-promoters exert their expected effects
of ceasing hair loss and enhancing hair regrowth [51].
As a consequence, clinically speaking, there is an
increased number of patients with “great expectations”
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who, encounter plenty of disappointments after the
treatment [52,53].
Evaluation of hair loss and hair regrowth
Unfortunately, researchers do not have a
standardized method to assess hair regrowth in vivo.
Possible tools include scales of measuring hair regrowth
based on percentage evaluations that can be performed
with the naked eye (visualization and photographs of the
area of interest) or by trichoscopy [49]. These qualitative
assessments are limited in number, therefore, new, accurate
and minimally invasive procedures are still needed.
To explore the efciency of a topic substance in
inducing hair growth, in vivo, researchers usually analyze
the hair growing pattern in animal groups treated with
different substances, compared to control by using the
macroscopic aspect. The skin of the animals, usually the
dorsal part, is observed and photographed either every 3
days or at specic time intervals (day 1, 7, 14 and 21 after
depilation) in order to notice the start of hair regrowth
period and the hair regrowth pattern. There are several hair
regrowth potential scores, but one easy to use was described
by Matsuda et al: 0 = no hair growth, 1 = less than 20% of
hair growth, 2=20-39% of hair growth, 3=40-59%of hair
regrowth, 4=60-79% of hair regrowth, 5=80-100% of hair
regrowth [54]. Researchers also use self-designed scales
of hair regrowth, such as: Type 4 (high hair density, full,
thick fur), Type 3 (moderate hair density with no visible
skin area), Type 2 (low hair density, with the visualization
of the skin), Type 1 (uneven hair growth on the test area,
skin easily seen) [55].
Trichoscopy is performed with a hand held device
called dermatoscope, with polarized light to magnify and
allow inspection of the skin. A decrease of hair diameter
up to ten times or diameter variations can be detected by
trichoscopy, so a correct hair regrowth evaluation can be
As far as quantitative methods are concerned, an
area of 1 cm² of skin with regrown hair is cut and weighed
with an analytical balance for hair weight determination
To further investigate the hair growth promoting
effect of a certain substance, the histopathological
examination offers a precise and necessary evaluation tool
for hair regrowth. Usually, at the end of the treatment period,
the rats are sacriced and a skin biopsy is isolated in order
to examine the histological features. The skin thickness
and hair follicles localization in the dermis/subcutis can
be evaluated by microscopic photograph (magnication
x400). Taking into consideration the existent knowledge
about hair cyclicity, the anagen induction is calculated with
the formula: (number of follicles in subcutis)x100( number
of follicles in dermis). Previous microscopical studies
on animals showed an association of increasing skin
thickness, follicle count and macroscopic development of
skin pigmentation with anagen induction [26,31].
The hair growth cyclicity (anagen, catagen, and
telogen phases) can be used as a diagnosis tool for the
hair growth condition and also as a treatment assessment
method for the hair growth promoting agent.
Hair regrowth treatment
The insufcient insight into the basic mechanism
leading to alopecia together with therapies that failed to
cure it, determined scientists to developed large research
programs to overcome hair loss [57]. Despite the many
treatment alternatives that have been tested, hair loss
continues to remain a frequent dermatological condition.
Up to the present, pharmaceutical hair loss
management includes only two FDA approved hair loss
drugs: Finasteride and Minoxidil, both commonly used in
clinical practice [46,51,58].
The hair growing effect of Minoxidil has been
accidentally discovered, as this antihypertensive oral drug,
caused side effects such as increasing hair growth on the
scalp or even darkening the ne body hairs. The 2% topical
formulation was approved by the FDA in the 1990s for use
in treating androgenetic alopecia in men (for central/vertex
hair loss only) and in females as well (in female pattern hair
loss) [59]. The 5% formulation is allowed only for males
and the foam version is associated with 70% self-reported
Minoxidil slows or stops hair loss and promotes
hair growth because it is a vasodilator that increases
the cutaneous blood ow to the scalp [60]. It is also a
potassium channel opener, causing hyperpolarization of
cell membranes, allowing more oxygen, blood and nutrients
to reach the follicle [61]. Minoxidil contains an N-oxide
group able to release NO, and besides being a vasodilator
[62], it also acts as a nitric oxide agonist. However, it has
no therapeutic action on the hormonal and genetic causes
of hair loss.
Minoxidil usual dosage is 1 mg per day, applied
topically, with slight massage on the affected area of the
scalp and no contact with water allowed for at least 4 hours
after application [63,64]. Minoxidil must be used as a
continuous support for the hair follicles, otherwise the hair
regrowth will ceases and hair loss will begin again in 30 to
60 days if Minoxidil treatment is stopped for more than 6
months [65]. Several studies have shown that the efcacy
of Minoxidil ranges from 20-40%, causing discontinuity of
treatment in the majority of patients [66].
Finasteride is considered a dihydrotestosteron-
suppressing 5 alfa-reductase inhibitor, recommended for
male use only, in the treatment of androgenetic alopecia. It
acts by decreasing the serum levels of dihydrotestosteron,
stopping hair fall (in 48% of the cases) and stimulating
hair regrowth (in 51% of the cases). Studies showed that 1
mg Finasterid oral treatment has a similar efcacy as daily
topical Minoxidil application on the scalp, but their efcacy
is seen after at least 4 months of daily usage [67,68]. These
two treatments can be combined in order to boost the hair
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follicles, but both treatments must be performed a-la-
longue, if not, the hair regrowth effect will cease. Adverse
reactions are rare, still sexual dysfunctions were reported in
4% of the cases [69,70].
Given the temporary efcacy of Finasteride and
Minoxidil and the limited number of treatments available
in alopecia, it is a challenge to discover new therapies
in order to prevent hair loss and enhance hair regrowth
[69,70]. Some substances diminish the physiopathological
processes that induce hair loss, but clinical studies in this
respect are lacking.
Arginin stimulates microcirculation, bringing in
essential nutrients for hair bulb growth.
Aminexil 1.5% diminishes the rate of hair loss as
it reduces the accelerated aging of the roots by ghting the
process of brosis. It also maintains the elasticity of the
tissue surrounding the hair root and prevents the stiffening
of collagen sheets, in order to fasten the hair root within the
scalp [52,53].
SP94 peptide is captured by the root and turned into
the hair constructive elements for building up the ber from
root to tip.
B5 and B6 Vitamins function as cellular nutrients
that nourish the hair roots and help generating beautiful,
shiny hair, that becomes thicker and stronger from within
Thermal Spring Water that contains anti-free
radical Selenium, enhances the therapeutic action of
Madecassoside, which inhibits the local micro-irritation,
preventing the spreading to the capillary bulb [65].
Low Level Laser Therapy (LLLT) provides
a promising treatment option for patients, this
photobiomodulation produces a shifting of the follicles
from telogen (resting phase) to anagen (active phase),
preventing premature catagen development (hair falling
phase) [71-73]. LLLT, through its low power coherent
monochromatic red light, produces vasodilation and
increases ATP production, also determining a modulation
of Reactive Oxygen Species (ROS) and inammatory
mediators [74-76].
Hair regrowth studies in vitro
Human hair follicles are not proper research material
due to ethical problems, invasive methods and limited
amount of follicles that can be extracted for testing [77,78].
Cotsarelis et al., discovered that bald areas have the same
number of stem cells as the normal scalp and also noticed
that hair follicles decrease in size, but do not disappear.
In alopecia, one of the major issues would represent the
activation of stem cells converting to progenitor cells in the
affected areas of the scalp [79].
Researchers insist in nding new natural and
chemical agents, which may convert stem cells into
progenitor cells and generate terminal hair [79,80].
In vivo models (experiments performed on natural
animals and genetically manipulated models) as well in
vitro research (cultures of a cell type - dermal papilla or
organ culture of isolated cell follicles ) have been used
successfully, to obtain the data that we now possess about
the function of the hair follicle in health or under disease
Scientists may choose one of the two types of
experimental studies taking into consideration the purpose
of the research, the advantages and disadvantages it offers.
Hair regrowth studies in vivo
Animal models
For a better understanding of the physiopathological
processes involved in hair loss and regeneration, animal
models have been used in hair research since 1950 [87].
In vivo research on hair loss and regrowth was
performed so far on mice, rats, hamsters, rabbits and sheep
in laboratory conditions [88,89,90,91]. Lately, the interest
in hair growth promoting agents has grown considerably
and in the attempt to discover an ideal therapy for alopecia,
new treatments have been studied even in stump-tailed
macaque [92]. Still, researchers must take into consideration
the differences between species regarding the follicular
function and limited androgen-sensitive models [93]. The
periodic intervals of rodent hair cycles, particularly the
duration of the anagen phase are much more consistent and
less susceptible to iatrogenic inuences [94].
The normal hair cycling, including growth waves
and hormonal control were studied on Wistar Bratislava
rats and mice [95]. The black mouse C57BL/6 was used
for the skin-free pigment and early visible pigmented tips
of new anagen regrowth [91,96]. The C3H mouse model
was the most widely reported for hair growth promotion,
even thought the increased hair density of the animal
and the wave pattern hair cycle progression presented
disadvantages [95,96,97]. Laser therapy applied in C3H
mouse, 20 second daily, 3 times per week, induced a much
longer growth phase, after only 2 weeks of treatment, with
most of the follicles from the tested area being in anagen
hair growth phase [98].
The androgen action upon the hair follicles has been
studied on spontaneous and genetically engineered nude
mutant mice. Immunodecient mice (with T and B cells
deciencies) were used as models for autoimmune disease
mechanisms and androgenetic alopecia studies [96]. Also,
by inhibiting the rejection of foreign skin, human skin
grafts were applied and even rat dermal papillas continued
to produce hair after reimplantation in vivo on a rat model
Recently scientists discovered that a certain
progenitor cell population in mice is analogous to the
human cells. These mature cells were tested by injection
on immunodecient mice animal model and the results
showed the development of new hair follicles and increased
hair regrowth [98].
The Mesocricetus auratus (Golden hamster)
was used for macroscopic assessment (hair density
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dermatoscopy analysis) and microscopic evaluation (hair
diameter analysis) as an animal model for hear regrowth
Since Minoxidil 2% is thought to be the gold
standard treatment for hair loss, scientists consider the
validation of Minoxidil treatment on an animal model
as being very important. Several studies have shown
that topical Minoxidil affects the normal hair cycle by
shortening telogen, causing premature entry of the resting
follicles into anagen phase which will lead to an increased
hair follicle size [103,104].
Housing conditions
Usually animals of either sex and weight were used
in the studies. They were acclimatized to the experimental
room at a temperature of 23 degrees Celsius, in controlled
humidity conditions with a 12:12 h light and dark cycle for at
least 7-14 days prior to the experiment. Usually, there was an
individual housing or maximum 2 animals per cage (to avoid
licking) with access to standard laboratory diet and water
ad libitum. Following the experiment they were euthanized
according to the current regulations. Some experiments were
performed in triplicate for accurate results
Depilation methods
Experimental designs may ask for the whole back or
body of the animal to be shaved, or there may be only some
specic areas to be denuded for testing.
In Dr. Mester’s study, before each successive
treatment, the skin was depilated by shaving, procedure
that may induce mechanic stimulation of hair growth, as
previously reported in the literature. An experiment done
on adult rats proved that after the fur was dyed and shaved,
concluded that the regrowing hairs on the rat skin formed a
system of linear loops, that were closely correlated with the
shaving process [74,75].
In order to avoid this effect, some scientists do
not shave the tested area of the animal model before each
daily therapy. It has been also proved that physical factors
inuence the hair regrowth process: temperature triggers
fast regrowth after shaving.
Depilation-induced hair cycle has a strict course: 9
days after depilation, the hair follicles enter the nal stage
of the growth cycle (anagen VI). Around day 17 the follicles
enter the regression stage (catagen) and around day 20 after
depilation, follicles get to the resting stage (telogen) [30].
Besides shaving, there are also other methods for
depilation, such as a raisin mixture or a hair removal cream
[91, 105].
As a conclusion, we tend to rene our knowledge
on human hair diseases and hair regrowth by using proper
animal models. Hair research provides further insights
into the physiopathological pathways, genetic and cell
biochemical mechanisms that could promise the cure of
hair loss.
This paper was published under the frame of the
European Social Found, Human Resources Development
Operational Programme 2007- 2013, project no.
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... The immense psychological and sociological importance of hair contributes to an individual's outlook [1]. Hair loss greatly affects people's quality of life despite not being an innoxious condition [1][2][3]. Low self-esteem, depression, and social and psychological distortions are only some of the consequences of hair loss [3]. Whatever the underlying cause of hair loss, it has an indisputable impact on an individual's quality of life. ...
... Hair loss greatly affects people's quality of life despite not being an innoxious condition [1][2][3]. Low self-esteem, depression, and social and psychological distortions are only some of the consequences of hair loss [3]. Whatever the underlying cause of hair loss, it has an indisputable impact on an individual's quality of life. ...
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A person’s quality of life can be adversely affected by hair loss. Microalgae are widely recognized for their abundance and rich functional components. Here, we evaluated the hair growth effect of a green alga, Botryococcus terribilis (B. terribilis), in vitro using hair follicle dermal papilla cells (HFDPCs). We isolated two types of cells from B. terribilis—green and orange cells, obtained from two different culture conditions. Microarray and real time-PCR results revealed that both cell types stimulated the expression of several pathways and genes associated with different aspect of the hair follicle cycle. Additionally, we demonstrated B. terribilis’ effect on collagen and keratin synthesis and inflammation reduction. We successfully isolated a novel compound, methylated-meijicoccene (me-meijicoccene), and C32 botryococcene from B. terribilis to validate their promising effects. Our study revealed that treatment with the two compounds had no cytotoxic effect on HFDPCs and significantly enhanced the gene expression levels of hair growth markers at low concentrations. Our study provides the first evidence of the underlying hair growth promoting effect of B. terribilis and its novel compound, me-meijicoccene, and C32 botryococcene.
... Це може бути пов'язане зі змінами цитокінового профілю, викликаними депіляцією в лабораторних тварин [33], а в ранні строки після видалення волосся -зі загальним адаптаційним синдромом, який зазвичай супроводжується посиленням ПОЛ [34]. Вочевидь слід вважати, що хімічна депіляція великої ділянки тіла в тварин є значно серйознішим втручанням, ніж видалення волосся депіляційним кремом на обмеженій ділянці тіла в людини, що зумовлено міжвидовими особливостями функцій волосяного покриву та будови шкіри [35]. Адже описано, що застосування звичайних депіляційних кремів відомих брендів викликало в лабораторних мишей еритему та гістопатологічні зміни вже за експозиції 15-120 с [36]. ...
Захворювання або втрата волосся можуть суттєво впливати на добробут і якість життя. Відомо багато видів алопеції, але в кожному випадку патогенетична терапія спрямована на стимулювання анагену, затримку катагену, відновлення або підтримку належної густоти волосся. Міноксидил для місцевого застосування є одним з найвизнаніших засобів лікування алопеції, але його вплив на рівень оксидативного стресу під час терапії описано недостатньо.Мета дослідження – вивчити вплив місцевого застосування міноксидилу на показники оксидативного стресу під час регенерації волосся в тварин з хімічною депіляцією.Експерименти були виконані на 35 білих щурах-самцях. Патологію моделювали шляхом хімічної депіляції шкіри спини щурів площею 8 см × 4 см калію тіогліколатом. Лікування розпочинали відразу після депіляції, наносячи на шкіру депільованої ділянки 2 % розчин міноксидилу 1 раз на добу в дозі 30 мг/кг. Через 3 дні, 9 днів та 21 день після депіляції тварин виводили з експерименту шляхом термінальної крововтрати. Відростання волосся оцінювали в балах. У крові та гомогенаті шкіри визначали малоновий діальдегід (МДА) і 4-гідроксиалкеналі як продукти пероксидного окиснення ліпідів (ПОЛ), активність супероксиддисмутази (СОД) і каталази. Одержаний цифровий матеріал статистично обробляли шляхом однофакторного дисперсійного аналізу ANOVA з апостеріорним Тьюкі-тестом або за критерієм U Манна-Уітні.При лікуванні міноксидилом через 3 дні стан шерсті досліджуваної ділянки був таким самим, як при контрольній патології. Через 9 днів препарат сприяв тенденції до появи шерстного покриву з оцінкою 3 бали. Через 21 день у групі з експериментальною терапією переважав розвиток волосся в 4 бали (повна нормалізація), але різниця з контрольною патологією була не вірогідною. Відновлення після хімічної епіляції без лікування супроводжувалось накопиченням МДА, зниженням активності СОД та коливаннями активності каталази в шкірі ураженої ділянки та крові. Під дією міноксидилу в усі строки спостережень у шкірі відмічалось зниження вмісту МДА, підвищення активності СОД та зміни активності каталази, яка додатково зростала через 3 дні, нормалізувалась через 9 днів і була на рівні контрольної патології через 21 день. Поряд з цим, препарат призводив до зменшення накопичення продуктів ПОЛ та суттєвого збільшення активності СОД у крові порівняно з контрольною патологією, що за спрямуванням було подібне процесам у шкірі. Під впливом міноксидилу каталазна активність крові зростала в усі терміни спостережень.Отже, міноксидил за умов щоденного місцевого лікування втрати волосся демонстрував антиоксидантну дію в шкірі ураженої ділянки та крові. Виявлена особливість фармакодинаміки препарату може бути корисна за його клінічного застосування на тлі оксидативного стресу, викликаного старінням, хіміо- або радіотерапією.
... For example, ethnicity or breed may be involved in cotinine metabolism variability, as may the type and texture of hair [7,8,40]. Despite hair growth in mammals differing from humans due to the unsynchronized growth cycles [41], similar morphological characteristics and compositions to canine bulge area as well as similarities in follicular biomarker expression, make the dog a model close to humans [42]. Albeit modestly, urinary cotinine was reported to be related to fur length in dogs [13]. ...
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Simple Summary Smoking is a global health problem, recognized as being responsible for increased risk for many diseases. Pets cohabiting with smoking owners may be exposed to tobacco by inhalation, absorption, or ingesting residual smoke particles. Cotinine is a product of the endogenous metabolism of nicotine, and it is used as a biomarker of environmental cigarette smoke exposure in humans. In particular, cotinine in biofluids (blood, saliva, and urine) and hair provides information on short- and long-term smoke exposure, respectively. Despite the considerable evidence of the harmful effects of active and passive tobacco smoke, few studies have explored the relationship between secondhand smoke exposure and cotinine in dogs. This study aimed to measure cotinine concentration in the serum and hair of dogs that were exposed to the owner’s tobacco smoke and to compare it with that of unexposed dogs. Moreover, the influence of exposure intensity (number of cigarettes), age, weight, and sex on cotinine concentration was explored. Cotinine was significantly higher in exposed than unexposed dogs in serum and fur. A sex difference in the concentration of cotinine was also evidenced. These results confirmed the role of cotinine as a sentinel of cigarette smoke exposure in dogs with a different sex sensibility. Abstract The adverse health effects of both active and passive tobacco smoke have been well-known in humans for a long time. It is presumable that even pets, which intimately share the owner’s lifestyle, may be exposed to the same risks. This study aimed to detect and quantify cotinine (a metabolite of nicotine) in the serum and hair of dogs using a specific commercial ELISA immunoassay kit. A total of 32 dogs, 16 exposed and 16 unexposed to the owner’s smoke, were enrolled. The cotinine concentration was higher in the exposed than the unexposed group in both matrices (p < 0.001), with greater values in serum than in hair (p < 0.001). Exposed bitches had higher hair cotinine than male dogs (p < 0.001). Conversely, serum and fur cotinine concentrations were lower in female than male dogs of the unexposed group (p < 0.01). The exposure intensity, age, and weight of the dogs did not affect cotinine concentrations. A cut-off value of 2.78 ng/mL and 1.13 ng/mL cotinine concentration in serum and fur, respectively, was estimated to distinguish between the exposed and unexposed dogs. Cotinine was confirmed as a valuable marker of passive smoking also in dogs. Although owners do not perceive secondhand smoke as a risk for their dogs, greater awareness should be advisable, especially in pregnant animals.
... We have identified several natural products capable of restoring the age-related regenerative decline of stem cells in vitro (Fang et al., 2018;Geng et al., 2019b;Shan et al., 2021;Zou et al., 2021). We then utilized mice with HFs synchronized into the second postnatal telogen phase, a classic model for evaluating the efficacy of regenerative strategy in promoting hair growth (Chai et al., 2019;Orasan et al., 2016;Porter, 2003;Son et al., 2018), to test the effect of these compounds in vivo. Que, Met, and GA were separately delivered into the shaved dorsal skin of mice for continuous treatment (Chai et al., 2019;Weger and Schlake, 2005) (Fig. 1A). ...
Full-text available
Hair loss affects millions of people at some time in their life, and safe and efficient treatments for hair loss are a significant unmet medical need. We report that topical delivery of quercetin (Que) stimulates resting hair follicles to grow with rapid follicular keratinocyte proliferation and replenishes perifollicular microvasculature in mice. We construct dynamic single-cell transcriptome landscapes over the course of hair regrowth and find that Que treatment stimulates the differentiation trajectory in the hair follicles and induces an angiogenic signature in dermal endothelial cells by activating HIF-1α in endothelial cells. Skin administration of a HIF-1α agonist partially recapitulates the pro-angiogenesis and hair-growing effects of Que. Together, these findings provide a molecular understanding for the efficacy of Que in hair regrowth, which underscores the translational potential of targeting the hair follicle niche as a strategy for regenerative medicine, and suggest a route of pharmacological intervention that may promote hair regrowth.
... The risk of such adverse side effects increases with the length and repetition of anesthesia, which is unavoidable when performing longitudinal studies [21,23]. Additionally, the necessity to remove fur at the site of US examination can lead to behavioral alterations in rodents, as the fur, apart from thermoregulatory functions, is also used for signaling, communication, or defense [24,25]. Moreover, the correct needle placement into the tail vein of mice, during the injection of US contrast agents, is a crucial step. ...
Full-text available
Introduction: Ultrasound (US) imaging enables tissue visualization in high spatial resolution with short examination times. Thus, it is often applied in preclinical research. Diagnostic US, including contrast-enhanced ultrasound (CEUS), are considered to be well tolerated by laboratory animals although no systematic study has been performed to confirm this claim. Therefore, the aim of this study was to screen for possible effects of US and CEUS examinations on welfare of healthy mice. Additionally, the potential influence of CEUS and molecular CEUS on well-being and therapy response to regorafenib was investigated in breast cancer-bearing mice. Material and methods: 40 healthy Balb/c mice were randomly assigned for examination with US or CEUS (3x/week) for four weeks. Untreated healthy mice and mice receiving only isoflurane anesthesia served as controls (n= 10/group). Ninety-four 4T1 tumor-bearing Balb/c mice were allocated randomly to the following groups: no imaging, isoflurane anesthesia, CEUS and molecular CEUS. They either received 10 mg/kg regorafenib or vehicle solution daily by oral gavage. Animals were examined three times within two weeks. CEUS measurements were performed using phospholipid-microbubbles and phospholipid-microbubbles targeting the vascular endothelial growth factor receptor-2 were applied for molecular CEUS. Welfare evaluation was performed by daily observational score sheets, measuring the heart rate, Rotarod performance and fecal corticosterone metabolites twice per week. On the last day, pathological changes of serum corticosterone concentrations, hemograms, and organ weights were obtained. Moreover, a potential influence of isoflurane anesthesia, CEUS and molecular CEUS on regorafenib response in tumor-bearing mice was examined. Analysis of variance and Dunnett post hoc test were performed as statistical analyses. Results: Severity parameters were not altered after repeated US and CEUS examinations of healthy mice, but spleen sizes were significantly lower after isoflurane anesthesia. In tumor-bearing mice, no effect on animal-welfare after repeated CEUS and molecular CEUS could be observed. However, leukocyte counts and spleen weights of tumor-bearing mice were significantly lower in animals examined with CEUS and molecular CEUS compared to the control groups. This effect was not visible in regorafenib-treated animals. Conclusions: Repeated US and (molecular) CEUS have no detectable impact on animal welfare in healthy and tumor-bearing mice. However, CEUS and molecular CEUS in combination with isoflurane anesthesia might attenuate immunological processes in tumor-bearing animals and may consequently affect responses to anti-tumor therapy.
... According to Orasan et al. (2016a) "finasteride and minoxidil (2% or 5%) have temporary effects and unpredictable efficacy, better pharmacological options are necessary for managing hair loss" (Gordon, 2011). Orasan et al. (2016b) went on to review hair loss techniques and stated "further studies are required not only to compare the efficiency of different therapies, but more importantly to establish their long term safety" (p.327). ...
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Background: Hair loss affects men and women around the world. Objective: This study analyzed the efficacy of a hair formula named Lotus 39 by Valentino De Salva (Lotus 39) on hair loss. Methods: Men and women between ages 42 and 72 applied Lotus 39 to their scalp every day for 8 weeks. For ethical reasons, a nonrandomized controlled study protocol was selected Results: According to the data, Lotus 39 stops hair loss, causes an increase in vellus hair, and an increase total hair count. Limitations: No control was assigned due to funding, baseline pictures were taken at the onset of the study, during, and at the end of the study to draw a depiction of hair improvement over time. Conclusion: This study suggests that Lotus 39 improves the health of the scalp and hair. IRB Approval Status: Reviewed and approved by IntegReview IRB; approval #CRLNJ2019-0198
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Hair loss (alopecia) has a multitude of causes, and the problem is still poorly defined. For curing alopecia, therapies are available in both natural and synthetic forms; however, natural remedies are gaining popularity due to the multiple effects of complex phytoconstituents on the scalp with fewer side effects. Evidence-based hair growth promotion by some plants has been reported for both traditional and advanced treatment approaches. Nanoarchitectonics may have the ability to evolve in the field of hair- and scalp-altering products and treatments, giving new qualities to hair that can be an effective protective layer or a technique to recover lost hair. This review will provide insights into several plant and herbal formulations that have been reported for the prevention of hair loss and stimulation of new hair growth. This review also focuses on the molecular mechanisms of hair growth/loss, several isolated phytoconstituents with hair growth-promoting properties, patents, in vivo evaluation of hair growth-promoting activity, and recent nanoarchitectonic technologies that have been explored for hair growth.
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The number of people suffering from hair loss is increasing, and hair loss occurs not only in older men but also in women and young people. Prostaglandin D2 (PGD2) is a well-known alopecia inducer. However, the mechanism by which PGD2 induces alopecia is poorly understood. In this study, we characterized CXXC5, a negative regulator of the Wnt/β-catenin pathway, as a mediator for hair loss by PGD2. The hair loss by PGD2 was restored by Cxxc5 knock-out or treatment of protein transduction domain–Dishevelled binding motif (PTD-DBM), a peptide activating the Wnt/β-catenin pathway via interference with the Dishevelled (Dvl) binding function of CXXC5. In addition, suppression of neogenic hair growth by PGD2 was also overcome by PTD-DBM treatment or Cxxc5 knock-out as shown by the wound-induced hair neogenesis (WIHN) model. Moreover, we found that CXXC5 also mediates DHT-induced hair loss via PGD2. DHT-induced hair loss was alleviated by inhibition of both GSK-3β and CXXC5 functions. Overall, CXXC5 mediates the hair loss by the DHT-PGD2 axis through suppression of Wnt/β-catenin signaling.
Minoxidil has been used as an effective and cost-efficient topical treatment for androgenic alopecia. However, due to its poor water solubility, commercially available formulations contain alcohol and propylene glycol in a concentration that causes skin reactions such as irritation and dryness. Therefore, nanotechnology-based formulations can offer an alternative that might increase penetration and deposition of the drug in the skin while minimizing its adverse reactions. Minoxidil cubosomes (MXD-CUB) were prepared by melt dispersion emulsification technique according to full 23 factorial design. Three Independent variables, namely, the dispersed phase concentration, glyceryl monooleate: Poloxamer 407 ratio and Tween 80 concentration were tested. Particle size, polydispersity index and the zeta potential were the dependent variables. The optimized formula was investigated by transmission electron microscopy, x-ray diffractometry and in vitro release test. In vivo study included Draize test, histopathological examination, hair re-growth efficacy and confocal laser scanning microscopy (CLSM). Particle size, zeta potential and polydispersity index of the optimal MXD-CUB were measured to be 131.10±1.41 nm, -23.5±0.42 mV and 0.185±0.0, respectively, and its entrapment efficiency was 80.4±4.04 %. Draize test and histopathological testing proved safety and tolerability of MXD-CUB. In vivo hair regrowth study revealed greater hair growth boosting effect of the prepared cubosomes compared to minoxidil solution. CLSM proved superior penetration and retention of rhodamine B-loaded cubosomes in the skin compared to rhodamine B solution. Therefore, MXD-CUB can be a safe and effective dosage form of minoxidil that overcome the drawbacks of the commercial formulations.
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Low-level laser therapy (LLLT) may induce in vivo biostimulation and photobiomodulation. The study aimed to evaluate the hair regrowth effect of different LLLT devices on a rat model of alopecia, applied alone or associated with Neoptide topical treatment as a hair growth stimulator. Laser treatments were performed 3 times a week. Group I and group II were treated with Laser I (HairMax Professional 12) for 1 minute 30 seconds, respectively 3 minutes. Laser II (Laser D68-1 Marp) was applied for 1 minute 40 seconds in group III. Group IV received topical Neoptide 0,3ml daily and group V got Laser I for 3 minutes plus Neoptide. The hair regrowth process was evaluated using clinical macroscopic aspect, grown hair weight and histopathological examination for skin thickness, follicle count and % anagen induction. Results revealed that treatment with Laser I had a time depending stimulatory effect on hair regrowth, the longer exposure having a better effect. Laser II had a negative effect by inducing hair loss. Combined treatment Laser I plus topic Neoptide application induced better hair regrowth than laser or Neoptide alone. Conclusion: In experimental rat alopecia the combination of LLLT with Neoptide had a better hair regrowth effect than each alone.
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This study investigated on a rat model the hair regrowth effects of Low-Level Laser Therapy as monotherapy or concomitant therapy with topical application of two chemical treatments that are used in human patients with hair loss: Minoxidil 2% - Hairgrow (Dar Al Dawa Pharma/Amman, Jordan) and Neoptide (Ducray/ Boulogne, France). Results of hair regrowth evaluated by macroscopical images (photographs), trichoscopy (with a dermatoscope) and grown hair weight (from a surface area of 1cm2) revealed that Minoxidil 2% therapy was more efficient than Neoptide. Topical treatments were less efficient than LLLT exposure alone. Both combined therapies: LLLT plus Minoxidil 2% and LLLT with Neoptide induced better hair regrowth than topical applications. Our study proves that not all the products recommended for human use have the same hair regrowth efficiency on an animal model and that a combined therapy (laser plus topical substance) may bring supplementary benefits. © 2015, Universitatea Babes-Bolyai, Catedra de Filosofie Sistematica. All rights reserved.