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The importance of antioxidants and iron chelators for comprehensive photoprotection. · The Science of Skin

• 0:00
  SPEAKER_00: This episode is brought to you by Skin Suiticals, the number one medical aesthetic skincare brand worldwide, and the leader in antioxidant science.
• 0:08
  SPEAKER_00: To learn more, visit www.skinseuticals.com.
• 0:22
  SPEAKER_01: I'm Dr.
• 0:23
  SPEAKER_01: Patty Ferris.
• 0:24
  SPEAKER_01: I'm a board certified dermatologist, and I'm your host for this episode of Skin Care Confidential.
• 0:29
  SPEAKER_01: Just as a reminder, Skin Care Confidential is an extension of our medical meeting, the Science of Skin Care Summit.
• 0:35
  SPEAKER_01: It's a meeting that was designed to teach healthcare professionals about the science behind topical skincare products and how to utilize them in clinical practice.
• 0:44
  SPEAKER_01: Today I am so excited to be interviewing one of the world's experts on photoaging, Dr.
• 0:52
  SPEAKER_01: Shere Puissant.
• 0:54
  SPEAKER_01: I hope I pronounce it close.
• 0:56
  SPEAKER_01: Um she holds a doctorate in science in cancer biology from the University of Lausanne in Switzerland and is also recognized by the fellows of the Royal Higher Education Academy and the Royal Society of Biology in the United Kingdom since 2003.
• 1:13
  SPEAKER_01: She currently works as a reader in the pharmaceutics at the Department of Life Sciences, again at the University of Bath, where she also leads the skin photobiology group.
• 1:24
  SPEAKER_01: At present, she holds positions of Associate Dean at the Faculty of Science and the Director of the Innovation Center for Therapeutic Innovation of Bath.
• 1:33
  SPEAKER_01: She's internationally recognized for her world, for her work pioneering in the field of sun-mediated oxidative damage to the skin.
• 1:41
  SPEAKER_01: And boy, are we in for a treat.
• 1:44
  SPEAKER_01: I'm going to start this podcast by saying I am a fangirl of yours.
• 1:49
  SPEAKER_01: So I have read a lot of your work.
• 1:52
  SPEAKER_01: I was not aware that you were the first person who started looking at and discovered labile iron.
• 1:58
  SPEAKER_01: And we're going to go all through that.
• 2:00
  SPEAKER_01: It's so fascinating.
• 2:01
  SPEAKER_01: And I think it's a piece of the oxidative puzzle that many people are not familiar with.
• 2:06
  SPEAKER_01: So I'm really excited about this interview.
• 2:10
  SPEAKER_01: Why don't we just start off with some of the basics since you're so well versed in photobiology and maybe talk about just sun exposure and the role that it plays, obviously, particularly ultraviolet A and photo aging, and then maybe explain, you know, something about the longer wavelengths of light, which are becoming more important, visible light and infrared.
• 2:31
  SPEAKER_02: Thank you very much, Dr.
• 2:33
  SPEAKER_02: Faris, for giving me this opportunity.
• 2:38
  SPEAKER_02: Yes, uh, I'm I'm the person who works on the photo aging and UVA.
• 2:44
  SPEAKER_02: And uh here a lot of my colleagues they also call me Iron Lady because I also work in the field of photo aging and iron.
• 2:52
  SPEAKER_01: Oh, that's so cute.
• 2:55
  SPEAKER_02: So uh which is not very nice, but well, anyway.
• 2:59
  SPEAKER_02: Um I uh I work on the field of UVA for over 20 years because um I'm uh originally a specialist of oxidative stress, and because UVA was the oxidizing component of sunlight, uh this would mean that it would generate reactive oxygen species, which is also commonly called free radicals in the skin.
• 3:23
  SPEAKER_02: Um, it is an agent which can induce a lot of oxidative damage in the cells.
• 3:30
  SPEAKER_02: It means that this free radicals they can in the cells damage the fat, lipids, the protein, and also genetic material, DNA.
• 3:39
  SPEAKER_02: And as such, um the cells also develop a lot of antioxidant defense, so they have some things in their cells to actually protect and prevent them against these free radicals.
• 3:53
  SPEAKER_02: But uh for the individuals who go off onto the sunlight and for the prolonged exposure, uh this antioxidant defense are not sufficient, and therefore the damage uh gets uh into the cells and and sometimes um it uh creates other consequences.
• 4:14
  SPEAKER_02: If the cells which are damaged are eliminated, that's good for the individuals.
• 4:20
  SPEAKER_02: If the cells which are damaged they are not eliminated, they may uh proceed to photocarcinogenesis, which is basically the development of skin cancer.
• 4:32
  SPEAKER_02: And um therefore it's very important uh because of the nature of UVA and UVB of component of sunlight which are cumulative.
• 4:43
  SPEAKER_02: Each time you go to the sun, you get some damage there, and the damage doesn't disappear, so it stays there.
• 4:50
  SPEAKER_02: Uh, and each time you add on a bit more on that damage.
• 4:53
  SPEAKER_02: So it's important to pay attention to the sunscreens and also sun lotions and applying them, which by itself is another topic.
• 5:04
  SPEAKER_02: The problem that I faced 20 years ago, it was that most of the sun creams and sun lotions they had this SPF to some protection factor, which is a a way of um scoring the sun lotions for UVB protection.
• 5:23
  SPEAKER_02: But the there were a lot of you know um debate that the sun creams they they were not really protecting against UVA.
• 5:32
  SPEAKER_02: So over the last 20 years, a lot of uh effort has been gone to create a similar index for UVA, which is called UVA index, and and sometimes in UK they also refer this to as stars.
• 5:48
  SPEAKER_02: So uh we always recommend for people to use some protections which have you know high SPF to protection against UVB, but also to UVA, because UVA um for a star would allow that you know you get the uh good protection.
• 6:07
  SPEAKER_02: The sad story is that although most of the sound lotions and some creams now they have this ability to protect against UVB and UVA, people they don't apply them enough.
• 6:20
  SPEAKER_02: So if you want to get you know uh two milligram per centimeter square uh recommended amount of sun cream, uh, for example, for your face, you have to put a full pot of cream only on your face.
• 6:35
  SPEAKER_02: And nobody does this.
• 6:36
  SPEAKER_02: I don't do this either.
• 6:38
  SPEAKER_02: So it's hard to do.
• 6:42
  SPEAKER_02: Exactly.
• 6:43
  SPEAKER_02: So uh this brings the uh the topic of my research that maybe we should have some fail-safe mechanism that if people apply sun lotion but not enough, or go to the water, they towel themselves, they they actually eliminate a lot of this protection, then they should they should have something as uh not as a passive protection only with with this uh sound lotions, but with some things which are actually already absorbing their skin and actively there, they can protect them as a fail-safe mechanism.
• 7:20
  SPEAKER_02: And UVA being an oxidative agent, so logically you want to have antioxidants there.
• 7:27
  SPEAKER_01: Of course.
• 7:28
  SPEAKER_01: Yes.
• 7:28
  SPEAKER_02: Um but antioxidants by themselves they are not very strong because an antioxidant can actually neutralize a free radical in one round.
• 7:40
  SPEAKER_02: But if you have more UV exposure, or you have elements uh such as iron, which is a catalyst of you know, formation of highly reactive oxygen species, then you you will end up to have uh other components in addition to antioxidant to actually stop this vicious cycle of formation of free radicals.
• 8:04
  SPEAKER_01: Let's go back a little bit about the labile iron piece.
• 8:08
  SPEAKER_01: Where does that iron come from?
• 8:10
  SPEAKER_01: And then how does it create reactive oxygen species?
• 8:15
  SPEAKER_02: Well, um, all the cells they they need iron, so every cell naturally has some free iron.
• 8:23
  SPEAKER_02: So this free iron is necessary for cell division, uh, it also is necessary for uh heme containing proteins in the cells.
• 8:34
  SPEAKER_02: Some of them are also antioxidants, such as catalase, which is a you know iron-containing enzyme.
• 8:39
  SPEAKER_02: But the problem is that um uh uh because iron uh in the free form can be toxic because it can actually participate in the formation of hydoreactive uh uh uh oxygenate uh species, that's why iron has to be contained.
• 8:58
  SPEAKER_02: So there is a huge molecule in cells which is called ferritin, and this protein actually, which is has 24 subunits of heavy light and is a quite massive molecule, actually uh is responsible to uh mop this extra iron in the cells and actually keep them in a free form if you want as a volt of iron, and and when it's necessary, it can you know release it uh to the cells to be used.
• 9:30
  SPEAKER_02: Uh so ferritin is usually in the cytosol, and after 24 to 48 hours, depending on the cell line, it becomes old.
• 9:40
  SPEAKER_02: So it is, you know, with the chaperone, it goes to the lysosomes, it gets degraded by specific proteases in the lysosomes, and is iron is released.
• 9:50
  SPEAKER_02: And this iron is actually then used in the cell for other processes.
• 9:56
  SPEAKER_02: Um skin cells are exposed to UVA, we just find out that uh because UVA is a strong membrane-damaging agent because of the formation of free radicals, it not only damages the lipids of the plasma membrane, but also it damages uh the membranes of the subcellular organelles, notably lysosomes, and as such, uh it releases these proteases, which are supposed to be in the lysosome to degrade, you know, the old proteins and recycle its iron and so on.
• 10:35
  SPEAKER_02: Uh, they are actually pathologically released to the cytosol, so it starts actually degrading any proteins that they have as substrates, and one of them is ferritin.
• 10:46
  SPEAKER_02: So upon UVA, we found that pathologically, ferritin is degraded in the cytosol, so it releases all this iron which has been safely sequestered within its shell, actually, to the cytosol.
• 11:01
  SPEAKER_02: And because UVA also generates at the same time uh free radicals, so the combination and the presence of simultaneously having free iron and reactive oxygen species cause a sort of a specific type of reactions, which are called phenton chemistry type reactions.
• 11:22
  SPEAKER_02: And if you have hydrogen peroxide, which is usually uh produced by UVA in the vicinity of iron and in the vicinity of the membranes, then you would get you know uh formation of hydroxyl radicals, which is the most vicious type of free radical in the cell.
• 11:42
  SPEAKER_02: Right.
• 11:43
  SPEAKER_02: It has a short half-life of 16 femtoseconds, but is so uh potent, it looks like you know, one of these agents you see in these uh computer games, you know, these agents which are running and you know destroying everything.
• 12:01
  SPEAKER_02: So within this 16 fentase, it can damage uh lipid protein DNA and does a lot of irreversible damage.
• 12:11
  SPEAKER_02: So that's why iron is is is very you know dangerous in the UVA and and often is overlooked, unfortunately.
• 12:21
  SPEAKER_01: Yeah, I I think um it's something that people oftentimes are not aware of.
• 12:26
  SPEAKER_01: So this sets up obviously the discussion of chelators that can chelate iron.
• 12:32
  SPEAKER_01: And I know that you've published recently done some studies in this area.
• 12:36
  SPEAKER_01: So talk about maybe some of the dual-functioning antioxidants and you work with ferulic acid, for example.
• 12:42
  SPEAKER_02: Yes, uh absolutely.
• 12:44
  SPEAKER_02: Well, we originally started uh because iron is important in photodamage by UVA, so we started to look at uh some synthetic chelators, some of you know, even clinical chelators.
• 12:59
  SPEAKER_02: But these are so strong chelators that if you add them to skin, it can also stop you know the overall uh normal function of the cells, which which routinely needs iron.
• 13:12
  SPEAKER_02: So, and also uh because of the consumer market, people are now taking any product in a shelf and they want to see what is in it, they don't want anything chemical, preservatives, and so on.
• 13:26
  SPEAKER_02: So natural products are you know the future, but then the natural product, as I as I mentioned, if you if they have only antioxidant activity, this is not enough.
• 13:38
  SPEAKER_02: Because iron is present in UVA really in UVA um after UVA exposure.
• 13:46
  SPEAKER_02: Therefore, if you if you only want to neutralize free radicals because of addition of iron there, you will have again formation of free radicals right away.
• 13:57
  SPEAKER_02: So therefore, um one should look for the products which have this dual function of not only having a potent antioxidant activity, but also having at least some iron binding capability so that it can mop iron, not deplete the cells of iron, but actually adjust the iron which has been released after UVA.
• 14:23
  SPEAKER_02: So this is a sort of a program uh in my lab that we are following up for for a while now.
• 14:32
  SPEAKER_02: We are actually screening a tremendous amount of you know, polyphenols, antioxidants, and so on.
• 14:40
  SPEAKER_02: So and one of the ones that recently we found out in collaboration with Ischioticals, uh it was this exciting uh molecules of ferolic acid, uh, which which because of their uh structure, they are supposed to have act as antioxidant and also iron cylator, natural iron cylator to mop the iron and also neutralize the free radicals.
• 15:09
  SPEAKER_02: And uh and actually we have done a bit of um uh experiments with them, and we find out that the the ferrulic acid is a very good antioxidant and an excellent iron cylinder.
• 15:26
  SPEAKER_02: When we pre-treat the cells with this compound, we can not only bring down uh the labile iron uh just without UVA radiation, but after UVA radiation, we adjust this damaging iron which is released in addition to its antioxidant activity, uh giving us a very good protection against UVA.
• 15:51
  SPEAKER_01: I love that.
• 15:52
  SPEAKER_01: That's so fascinating.
• 15:53
  SPEAKER_01: And it's a natural compound.
• 15:54
  SPEAKER_01: Yes, exactly.
• 15:56
  SPEAKER_01: People turn it over and look at the back of the label, they're not gonna be scared of it.
• 16:02
  SPEAKER_00: This episode is brought to you by Skin Suiticals, the number one medical aesthetic skincare brand worldwide, and the leader in antioxidant science.
• 16:11
  SPEAKER_00: To learn more, visit www.skinseuticals.com.
• 16:19
  SPEAKER_01: Now, are all polyphenols chelators?
• 16:23
  SPEAKER_01: Isn't the structure what makes them be able to chelate?
• 16:26
  SPEAKER_02: Yes, uh, I mean, some of them are like natural catechols, uh which is you know a sort of chelators, and some of them they are they don't have catecholic structure, but because they have some hydroxyl uh you know function here and there, they can actually act uh uh as a ligand for for for iron.
• 16:48
  SPEAKER_02: Yes.
• 16:49
  SPEAKER_01: So interesting.
• 16:50
  SPEAKER_01: And it again, the dual function is so great, and they also many of them, well, they all up regulate nerve too.
• 16:57
  SPEAKER_01: So they increase your own intrinsic antioxidants.
• 17:00
  SPEAKER_01: So as I think about it, I'm thinking they're kind of like a triple threat.
• 17:03
  SPEAKER_01: Yes, quelching free radicals, they're chelating iron, and they're also increasing your own enzymatic antioxidants.
• 17:09
  SPEAKER_01: I love it, it's it really connects the dots for me.
• 17:13
  SPEAKER_01: Talk about you also did a study that you published or that you presented, I think, at EADB, where you looked at C and E, and I think it was actin.
• 17:22
  SPEAKER_01: Yeah, talk about that study.
• 17:25
  SPEAKER_02: Yes, of course.
• 17:26
  SPEAKER_02: Um vitamin C and vitamin E, they are very potent antioxidants.
• 17:32
  SPEAKER_02: Uh, and their combination is always, you know, very much uh protective against UVA.
• 17:40
  SPEAKER_02: And uh and also for the visible light and near infrared, because visible light and near infrared, they also have uh oxidative component and they generate reactive oxy species so they can have a protection for them too.
• 17:55
  SPEAKER_02: That's what we are looking also at the moment on them.
• 17:59
  SPEAKER_02: Uh so vitamin E is a uh lipid peroxidation chain blocker.
• 18:06
  SPEAKER_02: Uh so when you have iron release in the cells, uh you will also generate single oxygen, this too start damaging the membranes and creating a sort of a uh um pre-radicles based on lipids, which are like alcoxils, and they can they can damage and actually make holes in the uh plasma membrane.
• 18:34
  SPEAKER_02: And and this damaging effect obviously, first of all, bring extracellular media to the cells so they can swell, they can die by necrosis, and if it does not, it creates any, very vulnerable cells and damage cells at all.
• 18:51
  SPEAKER_02: And in terms of you know, skin derma uh component, having lipid peroxidation is the you know uh just a very strong sign of damage.
• 19:02
  SPEAKER_02: So vitamin E would actually stop the formation of this lipid peroxides, and as such, it is a very strong antioxidant.
• 19:15
  SPEAKER_02: But we also find that because it's a very protective, both vitamin C and vitamin E, by themselves, they protect the cells again against UVA-induced photodamage, not only in the plasma membrane, but also in the subcellular organelles.
• 19:33
  SPEAKER_02: And as such, they actually protect uh the skin cells against UVA.
• 19:40
  SPEAKER_02: So now if you add to this combination also something like ectoin, which is known as a membrane stabilizer, you are actually solidifying your protection, you are consolidating the fact that you have vitamin C and vitamin E to stop the lipid peroxidation, and uh ectoin, which which which keeps the membrane integrity as it as it is.
• 20:07
  SPEAKER_02: So together we found out that they are a very good combination to ensure that the skin cells actually survive and are protected against UVA.
• 20:20
  SPEAKER_02: So they have very strong uh activity, and because they protect the lysosomal membranes against UVA, they can they are also actually uh uh protecting against UVA-induced iron release, which is also very important.
• 20:37
  SPEAKER_01: So interesting.
• 20:38
  SPEAKER_01: Um, you've done some really innovative work creating iron chelators, for example, light-activated iron chelators.
• 20:45
  SPEAKER_01: Talk about those.
• 20:46
  SPEAKER_01: I think that was so fascinating.
• 20:49
  SPEAKER_02: Well, the the light-activated chelators actually uh stems from the fact that we found that strong chelators by themselves, if you add them to the skin, they start, you know, mopping iron when even when you don't go uh to the sunlight.
• 21:07
  SPEAKER_02: So uh we decided that this is not like a very very safe way, so we should have some procolator which can only be activated when you go to the sunlight, and the skin actually experiences a damaging dose of UVA, uh, which I think is very good.
• 21:27
  SPEAKER_02: Uh, and and we've we first uh did the first generation where you had a procolator with a caging moiety, which was photolabile, so it could lead uh to not let any iron chalation activity, but uh upon UVA, this photolabile you know, moiety would have detached.
• 21:48
  SPEAKER_02: So in the first generation, this photolabal moiti had no biological function.
• 21:54
  SPEAKER_02: But in the second generation, we started to use hydroxycinamic acid.
• 22:00
  SPEAKER_02: It's where this component actually, after uh releasing by UVA, was converted to ambeliferon, uh, which is a natural antioxidant, and also ion chylator.
• 22:14
  SPEAKER_02: So we had uh we called a multifunctional light-activated chelator, so we had a chylator which also releases again natural uh antioxidant and chylator at the same time.
• 22:28
  SPEAKER_02: So and then from then on, we also realized that the mitochondria is also a very important organ and vital, and damage to mitochondria is very important.
• 22:43
  SPEAKER_02: Uh so it was a lot of debate to say that because mitochondria it was where the heme and iron surfacoclusters were synthesized, it it should have been a good destination of label iron, and because of the presence of a big pool of label iron there, maybe this organ is very susceptible to sunlight.
• 23:06
  SPEAKER_02: So we started uh to work in collaboration with King's College London to design some chilators which were uh targeted directly to the mitochondria to see whether by protecting the mitochondria we can actually get better protection.
• 23:26
  SPEAKER_02: And actually, the kind of a compounds that we made, they provided an unprecedented protection against UVA, even at very high doses.
• 23:37
  SPEAKER_02: So that would mean the mitochondria label iron was very important, and if you mop them, you actually protect the cells against uh mitochondria damage and UVA-induced uh cell deaths, really.
• 23:52
  SPEAKER_01: Mitochondria makes so much ROS itself, you know, it's just a little factory for reactive oxygen species.
• 24:00
  SPEAKER_01: So exactly that's super interesting.
• 24:03
  SPEAKER_01: Um maybe in conclusion, just what do you see as the future of I well let me ask you one other question.
• 24:10
  SPEAKER_01: What about pollutants?
• 24:11
  SPEAKER_01: I know some pollutants bring in they they serve as Trojan horses, bringing in things like iron.
• 24:18
  SPEAKER_01: Is that iron relevant?
• 24:20
  SPEAKER_01: I mean, can it participate in the fentan reaction?
• 24:22
  SPEAKER_01: Yes, and give us bad reactive oxygen species like hydroxyl radical?
• 24:27
  SPEAKER_02: Uh yes, we we think that, and uh there are a lot of studies, you know, some done by Giuseppe Valacci, they have shown actually that, you know, uh with iron cylators such as the spherox, I mean, you can actually mop uh the uh particulate matter, you know, mediated uh damage uh by sunlight to the skin cells.
• 24:50
  SPEAKER_02: So uh again, another find is a fascinating, you know, connection between the iron and foot damage related to pollution, also.
• 24:59
  SPEAKER_01: Yeah, that's so interesting.
• 25:01
  SPEAKER_01: Um Giuseppe Volaki's done so much good work on pollution, and I had the pleasure of interviewing him as well.
• 25:08
  SPEAKER_02: So I like a very entertaining site.
• 25:11
  SPEAKER_01: He really is.
• 25:11
  SPEAKER_01: The reason I became interested in your work is Giuseppe and I were writing a paper together a couple of years ago, and we were trying to put forward a more current uh way to protect the skin from environmental aggressors.
• 25:22
  SPEAKER_01: And I came across chelation, and you're all your work, and I'm like, you have to talk about this, Giuseppe.
• 25:28
  SPEAKER_01: And he's like, of course, of course.
• 25:29
  SPEAKER_01: And then he explained to me how pollutants do the same type of thing.
• 25:32
  SPEAKER_01: And I was, again, totally unaware of that piece of the puzzle.
• 25:36
  SPEAKER_01: So I see this as really important work because as dermatologists, we need to be kept abreast of really what is the most current way to protect the skin.
• 25:46
  SPEAKER_01: And as you mentioned, we all use UV filters, we all recommend antioxidants, but now we might want to be thinking about which antioxidants might also provide chelating benefits.
• 25:57
  SPEAKER_01: Do you see this as part of the paradigm as we move forward clinically?
• 26:02
  SPEAKER_02: Absolutely, because more and more also, you know, uh label iron has been shown to play a you know a key role in a lot of uh iron-related disorders such as cancer, diabetes, neurodeteptive disease.
• 26:18
  SPEAKER_02: So I think um, and there are a lot of studies that they are using natural uh antioxidants with chelating capabilities also for you know as a therapeutic approach for this disease.
• 26:33
  SPEAKER_02: So this this is something uh we are we are also working um as as part of our you know commitment to iron.
• 26:42
  SPEAKER_02: And um at the moment we have uh designed a series of iron sensors which can uh uh measure specifically the iron in in different compartments of the cells, in the cytosol, in the mitochondria, in the lysosomes, and in the nucleus.
• 27:00
  SPEAKER_02: And uh we call them, you know, we are trying to get the label ironome signature uh of cells, uh, not only in the healthy cells, because we find out that when individuals have you know a higher label ironome, they are highly sensitive to sunlight.
• 27:20
  SPEAKER_02: So this can be used, you know, for personalized sun protection or as an index uh for the sun sensitivity.
• 27:27
  SPEAKER_02: But also, we are now looking at the labile iron signature of a lot of um, you know, uh disease uh which are related to skin or not.
• 27:38
  SPEAKER_02: So we think this iron is important, and hence they call me Iron Lady because I keep working on iron.
• 27:47
  SPEAKER_01: Well, you you are the iron lady, that's for sure.
• 27:51
  SPEAKER_01: This is a major discovery and a very important piece of the puzzle.
• 27:55
  SPEAKER_01: I want to thank you for coming on Skincare Confidential.
• 27:58
  SPEAKER_01: I'm honored to have you.
• 27:59
  SPEAKER_01: I've learned so much.
• 28:01
  SPEAKER_01: I'm actually writing a talk on antioxidants, and I'm gonna add chelation to it.
• 28:05
  SPEAKER_01: So I just learned a lot of things from you.
• 28:08
  SPEAKER_01: I appreciate it.
• 28:09
  SPEAKER_01: I thank everybody for listening.
• 28:11
  SPEAKER_01: I hope everybody has a great day, and thanks so much again for your time and your expertise.
• 28:17
  SPEAKER_02: Thank you very much, Dr.
• 28:18
  SPEAKER_02: Faris.
• 28:18
  SPEAKER_02: It was a pleasure here, and thank you.
• 28:20
  SPEAKER_02: It was very interesting for me, this discussion.
• 28:23
  SPEAKER_02: Thank you.
• 28:24
  SPEAKER_01: Thank you.
• 28:26
  SPEAKER_00: This episode is brought to you by Skin Suticles, the number one medical aesthetic skincare brand worldwide, and the leader in antioxidant science.
• 28:35
  SPEAKER_00: To learn more, visit www.skinseuticals.com.