Role of mitochondrial ATP-sensitive potassium channel-mediated PKC-ε in delayed protection against myocardial ischemia/reperfusion injury in isolated hearts of sevoflurane-preconditioned rats

This study aimed to determine the role of mitochondrial adenosine triphosphate-sensitive potassium (mitoKATP) channels and protein kinase C (PKC)-ε in the delayed protective effects of sevoflurane preconditioning using Langendorff isolated heart perfusion models. Fifty-four isolated perfused rat hearts were randomly divided into 6 groups (n=9). The rats were exposed for 60 min to 2.5% sevoflurane (the second window of protection group, SWOP group) or 33% oxygen inhalation (I/R group) 24 h before coronary occlusion. The control group (CON) and the sevoflurane group (SEVO) group were exposed to 33% oxygen and 2.5% sevoflurane for 60 min, respectively, without coronary occlusion. The mitoKATP channel inhibitor 5-hydroxydecanoate (5-HD) was given 30 min before sevoflurane preconditioning (5-HD+SWOP group). Cardiac function indices, infarct sizes, serum cardiac troponin I (cTnI) concentrations, and the expression levels of phosphorylated PKC-ε (p-PKC-ε) and caspase-8 were measured. Cardiac function was unchanged, p-PKC-ε expression was upregulated, caspase-8 expression was downregulated, cTnI concentrations were decreased, and the infarcts were significantly smaller (P<0.05) in the SWOP group compared with the I/R group. Cardiac function was worse, p-PKC-ε expression was downregulated, caspase-8 expression was upregulated, cTnI concentration was increased and infarcts were larger in the 5-HD+SWOP group (P<0.05) compared with the SWOP group. The results suggest that mitoKATP channels are involved in the myocardial protective effects of sevoflurane in preconditioning against I/R injury, by regulating PKC-ε phosphorylation before ischemia, and by downregulating caspase-8 during reperfusion.

The effect of 5-HD on expression of PKC-alpha in rats of chronic hypoxic pulmonary hypertension / 中国应用生理学杂志

<p><b>OBJECTIVE</b>To investigate the effect of mito chondrial K(ATP) channels (mitoK(ATP)) inhibitor 5-hydroxydecanoate(5-HD) on chronic hypoxic pulmonary artery hypertension (CHPAH) rats and its underlying mechanisms.</p><p><b>METHODS</b>Forty-eight male SD rats were equally divided into 4 groups randomly (n=12): normal group, hypoxia group, hypoxia + 5-HD group, hypoxia + Diazoxide group. Except the first group, the other three groups were put into hypoxic [O2 (10.0% +/- 0.3%] and nonrmobaric chamber for four weeks to establish chronic hypoxic model and received different interference. When the interference completed, right heart catheter was used to detect the mean pulmonary arterial pressure (mPAP) of each rat and PKC-alpha mRNA expression in pulmonary arteries was detected by reverse transcription-polymerase chain reaction (RT-PCR) and protein expression by Western blot.</p><p><b>RESULTS</b>(mPAP was much higher in hypoxia group than that in normal group (P < 0.01) while in hypoxia + 5-HD group and hypoxia + diazoxide were decreased significantly compared to hypoxia group (P < 0.01). (2) The protein and mRNA levels of PKC-alpha in the hypoxic group were higher than those in normal group (P < 0.05).</p><p><b>CONCLUSION</b>5-HD plays a protective role on CHPAH. The mechanism of its effect may be attributed to inhibiting MitoK(ATP).</p>

Polyphenol (-)-Epigallocatechin Gallate during Ischemia Limits Infarct Size Via Mitochondrial K(ATP) Channel Activation in Isolated Rat Hearts

Polyphenol (-)-epigallocatechin gallate (EGCG), the most abundant catechin of green tea, appears to attenuate myocardial ischemia/reperfusion injury. We investigated the involvement of ATP-sensitive potassium (K(ATP)) channels in EGCG-induced cardioprotection. Isolated rat hearts were subjected to 30 min of regional ischemia and 2 hr of reperfusion. EGCG was perfused for 40 min, from 10 min before to the end of index ischemia. A nonselective K(ATP) channel blocker glibenclamide (GLI) and a selective mitochondrial K(ATP) (mK(ATP)) channel blocker 5-hydroxydecanoate (HD) were perfused in EGCG-treated hearts. There were no differences in coronary flow and cardiodynamics including heart rate, left ventricular developed pressure, rate-pressure product, +dP/dt(max), and -dP/dt(min) throughout the experiments among groups. EGCG-treatment significantly reduced myocardial infarction (14.5+/-2.5% in EGCG 1 micrometer and 4.0+/-1.7% in EGCG 10 micrometer, P<0.001 vs. control 27.2+/-1.4%). This anti-infarct effect was totally abrogated by 10 micrometer GLI (24.6+/-1.5%, P<0.001 vs. EGCG). Similarly, 100 micrometer HD also aborted the anti-infarct effect of EGCG (24.1+/-1.2%, P<0.001 vs. EGCG ). These data support a role for the K(ATP) channels in EGCG-induced cardioprotection. The mK(ATP) channels play a crucial role in the cardioprotection by EGCG.

The effect of mitochondrial adenosine triphosphate-sensitive potassium (K(ATP)) channel blocker on ischemic preconditioning in hypoxic-ischemic brain injury model of neonatal rat / 대한마취과학회지

BACKGROUND: A brief episode of cerebral ischemia confers transient ischemic tolerance to a subsequent ischemic challenge that is otherwise lethal to them. This study was purposed to evaluate the effect of mitochondrial adenosine triphosphate-sensitive potassium (KATP) channel blocker on ischemic preconditioning in hypoxic-ischemic brain injury model of neonatal rat. METHODS: Seven-day old Sprague-Dawley rat pups were used. The rats were divided into five groups; control group (n = 91), pretreatment hypoxic preconditioning group (n = 43), pretreatment ischemic preconditioning group (n = 52), hypoxic preconditioning group (n = 39), and ischemic preconditioning group (n = 51). Rats in the pretreatment hypoxic preconditioning group and pretreatment ischemic preconditioning group were treated by an intraperitoneal injection with 5-hydroxydecanoate (60 mg/kg). Thirty minutes after injection, right common carotid artery was temporarily occluded for ten minutes in pretreatment ischemic preconditioning group. Rats in the pretreatment hypoxic preconditioning group and hypoxic preconditioning group underwent hypoxia (8% oxygen/92% nitrogen) for four hours. Twenty-four hours after the preconditioning, rats from all groups were exposed to right common carotid artery ligation followed by 2.5 hour hypoxia. On the 1st day after hypoxic-ischemic brain injury, terminal deoxynucleotidyltransferase-mediated dUTP-biotin nick end-labeling (TUNEL) reaction was evaluate as apoptotic markers and triphenyl tetrazolium chloride (TTC) was done to measure necrotic tissue. All rats were sacrificed 2 weeks after hypoxic-ischemia brain injury and the brains were examined for morphologic study. RESULTS: There were no differenced in survival rate, infarct area, number of TUNEL positive cells and morphologic score either between hypoxic preconditioning group and pretreatment hypoxic preconditioning group or between ischemic preconditioning group and pretreatment ischemic preconditioning group. CONCLUSIONS: The results suggests that mitochondrial K(ATP) channel blocker, 5-hydroxydecanoate, does not change hypoxic-ischemic preconditioning in the neonatal rat.

Regulation of rat airway smooth muscle cell proliferation by mitochondrial ATP-sensitive K(+) channel in asthmic rats / 生理学报

The objective of this paper was to investigate the effect and mechanism of mitochondrial ATP-sensitive K(+) (MitoK(ATP)) channel on the proliferation of airway smooth muscle cells (ASMCs) in asthmic rats. Thirty-six Sprague-Dawley (SD) rats were randomly assigned into 2 groups (18 in each): (1) Asthma group: the asthmic rat model was established by ovalbumin (OVA) sensitization and excitation; (2) Normal group: rats were subjected to inhalation of equal amount of normal saline. The rat ASMCs were isolated from fresh lung tissues and cultured respectively as follows: (1) CONTROL GROUP: normal ASMCs were cultured under normoxia for 24 h; (2) Diazoxide group: normal ASMCs were cultured under normoxia for 24 h with diazoxide (an opener of MitoK(ATP) channel); (3) 5-HD group: normal ASMCs were cultured under normoxia for 24 h with 5-hydroxydecanoate (5-HD) (an antagonist of MitoK(ATP) channel); (4) Asthma group: Asthmic ASMCs were cultured under normoxia for 24 h; (5) Asthma + diazoxide group: Asthmic ASMCs were cultured under normoxia with diazoxide for 24 h; (6) Asthma + 5-HD group: Asthmic ASMCs were cultured under normoxia with 5-HD for 24 h. The mitochondrial membrane potential (ΔΨm) was detected using Rhodamine 123 (R-123). The level of reactive oxygen species (ROS) was detected by DCF fluorescence. The expression of nuclear factor-kappa B (NF-κB) mRNA was examined by RT-PCR. The proliferation and apoptosis of rat ASMCs were examined respectively by MTT colorimetric assay and cell cycle analysis. The results were as follows. (1) After exposure to diazoxide for 24 h, the R-123 fluorescence intensity, the ROS level, NF-κB mRNA expression and the MTT absorbance value (A value) in normal ASMCs were significantly increased, and the apoptosis of rat ASMCs was significantly decreased compared to the control group (P<0.05). However, there was no significant changes in those indices after the normal ASMCs had been exposed to 5-HD for 24 h. (2) In Asthma and Asthma + diazoxide groups, the R-123 fluorescence intensity, ROS level and the MTT A value were markedly increased, and the apoptosis was markedly decreased compared to control group (P<0.05). These changes were more obvious in Asthma + diazoxide group than those in Asthma group (P<0.05). 5-HD partly weakened the effect of asthma on the R-123 fluorescence intensity, ROS level and the MTT A value and the apoptosis of rat ASMCs (P<0.05). R-123 fluorescence intensity and NF-κB mRNA expression were positively correlated with ROS level. NF-κB mRNA expression was positively correlated with the MTT A value and negatively correlated with the apoptosis of rat ASMCs. All the results suggest that the opening of MitoK(ATP) channel followed by a depolarization of ΔΨm contributes to the increase in ROS level and NF-κB mRNA expression in rat ASMCs and to the unbalance between cell proliferation and apoptosis of ASMCs induced by asthma. This might be a mechanism of the development of airway remodeling in asthma.

Effects of diazoxide on Fas/FasL protein expressions in rat myocardium suffered from long-term hypothermic preservation / 生理学报

The purpose of this study was to investigate the effect of a mitochondrial ATP-sensitive potassium channel (mitoK(ATP)) opener, diazoxide (DE), on Fas/FasL protein expressions in rat heart suffered from long-term hypothermic preservation. The Langendorff isolated rat heart model was used. The hearts were stored in 4 °C Celsior solution with or without (control) DE for 8 h followed by 60 min of reperfusion. The recovery of rate-pressure product (RPP) was observed. Apoptotic cardiomyocytes were detected by TdT-mediated dUTP nick end labeling (TUNEL) technique. The expressions of Fas/FasL proteins were also analyzed by immunohistochemical method. The results showed that compared with the control group, DE (30 mmol/L) increased the recovery of RPP during reperfusion, reduced the percentage of apoptotic cells and the expressions of Fas and FasL proteins in rat hearts suffered from 8 h of hypothermic preservation. The above effects of DE were attenuated by a mitoK(ATP) channel inhibitor 5-hydroxydecanoate (5-HD). These results indicate that DE could alleviate rat myocardial injury induced by ischemia-reperfusion through reducing the expressions of Fas and FasL proteins via opening of mitoK(ATP)channel.

The Mechanism of R-PIA Induced Mechanical Antiallodynia in a Peripheral Neuropathic Rat / 대한마취과학회지

BACKGROUND: The injury by a nerve ligation produces a mechanical allodynia. The antiallodynic effect resulted from intrathecal administration of the adenosine analogues has been well known. ATP-sensitive potassium channel blockers have been known to reverse the effect of some antinociceptive drugs in animal and human studies. Therefore, the present study is to assess the relationship between antiallodynic effect of N6-(R)-phenylisopropyl adenosine (R-PIA) and mitochondrial ATP-sensitive potassium (mKATP) channel in a neuropathic pain model. METHODS: Allodynia was induced in male Sprague Dawley rats by the tight ligation of the left lumbar 5th and 6th spinal nerves. We tested the mechanical allodynia by pricking von Frey filaments to the left hind paw and assessed withdrawal thresholds of paw with up-down method. For the estimation of the antiallodynic effect of R-PIA, R-PIA (0.5, 1 and 2microgram) or saline were administered intrathecally.To investigate the reversal effect on antiallodynic effect of R-PIA, variable amounts of 5-hydroxydecanoate (5-HD, 20, 30 and 40 mg), mKATP channel blocker were administered intraperitoneally at 5 min prior to the intrathecal injection of 2microgram of R-PIA, and the degree of allodynia was assessed. RESULTS: The paw withdrawal threshold was gradually increased with increased dose of R-PIA and reached the maximum level with 2microgram R-PIA (P < 0.05). The increase of paw withdrawal threshold with 2microgram R-PIA was significantly reversed dose-dependently by intraperitoneal pretreatment of 20, 30 and 40 mg/kg 5-HD (P < 0.05). CONCLUSIONS: In our results, intraperitoneal injection of 5-HD before intrathecal injection of R-PIA had reversed the antiallodynic effect of R-PIA. This results suggest that the mechanism of mechanical antiallodynia induced by intrathecal injection of R-PIA may relate with the mK(ATP) channel in a rat model of nerve ligation injury.

Effect of postconditioning on rat hearts suffered from long-term hypothermic preservation / 浙江大学学报·医学版

<p><b>OBJECTIVE</b>To assess the effect of postconditioning on cardiac protection of rat hearts suffered from long-term hypothermic preservation.</p><p><b>METHODS</b>The Langendorff model of isolated rat heart was used. After 30 min of stabilization, the hearts were stored in 4 degrees C Celsior solution for 3 or 5 h followed by 60 min of reperfusion. Postconditioning was initiated by 3 cycles of 30 s ischemia followed by 30 s reperfusion at the beginning of subsequent persistent reperfusion. The recovery of cardiac contractile function and arrhythmia score were observed.</p><p><b>RESULTS</b>(1) Compared with control group, postconditioning increased the recovery of heart rate (HR), left ventricular systolic pressure (LVDP), maximal rise/fall rate of ventricular pressure (dP/dt(max)) and coronary flow (CF) and rate-pressure product (RPP) during reperfusion after 3 h of hypothermic preservation. However, left ventricular end-diastolic pressure (LVEDP) and the cardiac arrhythmia score during the first 10 min of reperfusion was significantly lower in 3 h postconditioning group than that in 3 h control group. (2) The rat hearts treated by postconditioning with 5-HD(100 micromol/L) abolished the amelioration of contract function induced by postconditioning. And it could also increase the cardiac arrhythmia score. (3) Compared with 5 h control group, the HR, LVDP,dP/dt(max), CF, LVEDP, RPP and the cardiac arrhythmia score were not significantly different in postconditioning treated hearts during reperfusion after 5 h of hypothermic preservation.</p><p><b>CONCLUSION</b>Postconditioning could provide the cardiac protection on 3 h hypothermic preserved rat hearts,but not on 5 h hypothermic preserved rat hearts. The cardiac protection effect might be partly associated with activation of selective mitochondrial ATP-sensitive potassium channel.</p>

The protective role and the mechanisms of puerarin on isolated rat heart during ischemia/reperfusion / 中国应用生理学杂志

<p><b>AIM</b>To determine whether the cardioprotection of puerarin (Pue) against ischemia/reperfusion (I/R) is mediated by mitochondrial transmembrane pore or channels.</p><p><b>METHODS</b>Male Sprague-Dawley rats were used for Langendorff isolated heart perfusion. The hearts subjected to global ischemia for 30 min followed by 120 min of reperfusion. Formazan, a product of 2,3,5-triphenyltetrazolium chloride (TTC), which is proportional to myocardial viability, was measured at 490 nm, and the level of lactate dehydrogenase (LDH) in the coronary effluent was measured to evaluate the cardiac injury.</p><p><b>RESULTS</b>The pretreatment with Pue at 0.24 mmol/L for 5 min before ischemia increased formazan content of myocardium, reduced LDH release, improved the recovery of the left ventricular developed pressure, maximal rise/fall rate of left ventricular pressure, left ventricular end-diastolic pressure and rate pressure product (left ventricular developed pressure multiplied by heart rate) and attenuated the decrease of coronary flow during reperfusion. Administration of atractyloside (20 micromol/L), an opener of mitochondrial permeability transition pore, for 20 min (first 20 min of reperfusion) and 5-hydroxydecanoate (100 micromol/L), the mitochondrial specific K(ATP) blocker, for 20 min before ischemia attenuated the protective effects of Pue.</p><p><b>CONCLUSION</b>The findings indicate that in the isolated rat heart, Pue protects myocardium against ischemia/ reperfusion injury via the opening of mitochondrial ATP-sensitive potassium channel and the inhibition of mitochondrial permeability transition pore opening.</p>

Comparision of Results of Sting Tests Using Various Kinds of Alpha Hydroxy Acids on Sensitive Skin / 대한피부과학회지

BACKGROUND: Users of cosmetics and skin care products often report adverse reactions ranging from itching, stinging and dryness to intense inflammatory responses such as erythema, wheals and rashes. Sensitive skin has been described as a skin type showing higher reactivity than normal skin, and it develops exaggerated reactions when exposed to internal stimulants and external irritants. The alpha hydroxy acids (AHAs), naturally occurring organic acids which include lactic acid, glycolic acid, citric acid, malic acid and tartaric acid are all kinds of noncorrosive irritants. The lactic acid sting test is widely accepted as a marker of sensitive skin and is employed for the selection of subjects experiencing invisible sensory irritation. OBJECTIVE: This study was performed to compare the results of sting tests conducted on the sensitive and nonsensitive skin group which had been exposed to various kinds of AHAs. METHOD: A total of 50 individuals (25 individuals with a sensitive skin group and 25 individuals with a nonsensitive skin group) were selected by the method of self-assessment questionnaires relating to sensitive skin. The subjects were tested on the face with 2 variables of 5 AHA types ( with or without Hilltop chamber occlusion), at 2 weeks intervals, for a total of 10 times. RESULTS: The positive response rate of stinging in the sensitive skin group was higher than that in the nonsensitive skin group for all tests except the glycolic acid sting test using Hilltop chamber (p<0.05). The mean value of sting scores in the sensitive skin group was higher than that in the nonsensitive skin group for all tests (p<0.05). CONCLUSION: Sting tests using various kinds of AHAs are a useful method in determining sensitive skin.

Estudos para a síntese do petrosinol e da amamistatina B / Studies on the synthesis of petrosinol and of amamistatin B

O petrosinol é um produto natural obtido a partir de esponjas do gênero Petrosia sp. Trata-se de um poliacetileno que posui atividade anti-HIV. A síntese deste composto, ainda não descrita na literatura, mostrou-se difícil. No presente trabalho são descritas as rotas sintéticas testadas para a obtenção do petrosinol. Foram feitas abordagens, totalizando sete, que consistiram na síntese de sistemas dicarbonílicos `alfa´, ß-insaturados, os quais se mostraram pouco reativos, que não permitiram a continuidade das rotas com esta abordagem, ou tentativas de construção de álcoois propargílicos, que neste caso, os intermediários de síntese se mostraram muito instáveis. A síntese do petrosinol necessita de mais estudos visando novas tentativas para se obter o sistema diol insaturado central presente na molécula, chave para a síntese total da mesma

A rapid hypochlorite method for extraction of polyhydroxy alkanoates from bacterial cells.

A new method has been standardized for extraction of polyhydroxy alkanoates from the bacteria, using sodium hypochlorite. This method is simple and quick as compared to the existing methods. Statistical analysis has proved the method to be reliable and reproducible.

Comparative Effects of Retin-A and Vitamin C on Photoaging Skin

Photoaging skin occurs as a result of long-term exposure to ultraviolet radiation. In contrast to intrinsic aging, skin changes of photoaging can be reversed by the topical use of skin care products. Several skin care products have now undergone sufficient evaluation and have a well-defined role in our practice. Retin-A and alpha hydroxy acids have a significant number of data available for evaluation; data for Vitamin C and antioxidants are still emerging. We conducted clinical trial to compare the anti-photoaging effects of Rein-A and Vitamin C in 25 women volunteers. Each formulation wes applied daily to the randomly assigned hemifaces over the 8-month study period. Comparative evaluations of anti-photoaging effects were made using subject self-appraisal questionnares, plastic surgeon's assessment, ultraviolet revelations, and histologic examinations. Subject self-appraisal and plastic surgeon's assessment showed predominance of Retin-A over Vitamin C. But both Retin-A and Vitamin C provided objective and subjective improvement in photodamaged facial skin and no significant difference was found between Retin-A and Vitamin C in histologic examinations.

Acido glicólico: agente despigmentante e rejuvenescedor / Glycolic acid: depigmenting agent and rejuvenating

A pigmentaçäo da pele, causada pela irradiaçäo da luz ultravioleta, como defesa contra a açäo carcinogênica da luz solar, pode levar ao envelhecimento precoce da pele e a uma hipercromia, cujo tratamento requer o uso de fotoprotetores, despigmentantes e rejuvenescedores. Recentemente, têm sido usadas várias substâncias para previnir e/ou tratar o envelhecimento cutâneo, bem como para diminuir a pigmentaçäo da pele. O hidroxiáxido mais comumente empregado em preparaçöes cosméticas e dermatológicas tem sido o ácido glicólico, pelas propriedades despigmentantes e rejuvenescedoras e pela eficácia que apresenta, em diferentes concentraçöes, quando incorporado a vários tipos de excipientes.

Piel y menopausia: efectos de la edad, estado hormonal y tratamientos / Skin and menopause: age effects, hormone state and treatment

El deterioro de la piel con la edad está influido por factores endógenos como el componente genéticos o la situación hormonal; y por exógenos como el tabaco o las radiaciones ultravioletas de la luz solar. Una piel deteriorada impacta fuertemente en la calidad de vida de una mujer, por lo que es relevante tener posibilidades de mejorarla. Los estrógenos actúan en la piel aumentando el ácido hialurónico, lo que produce una mayor hidratación de la dermis; esta edematización, asociada al aumento de la polimerización del colágeno que provocan los estrógenos, aumentan el grosor cutáneo; también estas hormonas inducen mayor formación de vasos en la piel, lo que se traduce en mayor actividad metebólica de la epidermis. Estos efectos explican que la terapia de reemplazo hormonal mejore la calidad de la piel, disminuyendo las arrugas y mejorando las características biomecánicas de la piel. Otras alternativas para atenuar el envejecimiento cutáneo pueden ser algunas terapias no endocrina como los ácidos alfa-hidroxilados y los ácidos retinoicos. La protección de las radiaciones solares y los cambios de hábitos nocivos para la piel, como el consumo de cigarrillo son medidas que deben aconsejarse a todas las pacientes

Bacteria isolated from a sugarcane agroecosystem: their potential production of polyhydroxyalcanoates and resistance to antibiotics

In this investigation, a sugarcane agroecosystem at a coastal tableland, in the northeast of Brazil, was screened to obtain bacteria strains able to synthesize poly-ß-hydroxyalkanoates (PHA), using sucrose as the main carbon source. The potential to synthesize PHA was tested qualitatively by Sudan Black staining of colonies growing in different carbon sources: sucrose, glucose, fructose, propionate and cellulose. In a typical sugarcane crop management system, the plantation is burned before harvesting and vinasse, a by-product of alchohol production, is used in a fertirrigation system causing, probably, selective pressures on the microbiota of natural environments. Eighty-two bacteria strains, belonging to 16 different genera and 35 different species, were isolated. The data showed that 11 strains (ca 13 per cent), nine of which belonging to the genus Pseudomonas, presented a strong Sudan Black staining in several carbon sources tested and, simultaneously, showed multiple resistance to antibiotics. Resistance to antibiotics is an advantageous feature for the biotechnological production of PHAs. The total number of isolates with multiple resistance to antibotics was 73, and 38 (per cent) of them belong to the genus, Pseudomonas. Among the isolates ca, 86 (per cent) and 43 (per cent) grew in the presence of 10-100U/ml of penicillin and/or 100-300 mg/ml of virginiamycin, respectively. These antiotics are utilized in the alcohol distillery we investigated. The results suggest that some agroecosystem environments could be considered as habitats where bacteria are submitted to nutritional unbalanced conditions, resulting in strains with potential ability to produce PHAs, and also, to an increase in the microbial diversity.

Cutaneous Irritation to Alpha Hydroxy Acids in Normal Human Skin / 대한피부과학회지

BACKGROUND: Alpha hydroxy acids (AHAs) are known to diminish corneocyte cohesion at the innermost levels of the stratum corneum and have been used in the treatment of various disorders of keratinization. However, their effect on skin barrier function and their irritant potential is not fully understood. OBJECTIVE: Our study was done to evaluate the skin irritancy of AHAs in normal human skin. METHODS: Patches with 1%, 5% and 10% solutions of lactic acid (LA) and glycolic acid (GA) were applied to the volar forearm of 20 healthy volunteers for 24 hours using large Finn chambers with filter paper. Visual scores, erythema (E-) index and transepidermal water loss (TEWL) were measured at 30 min, 24 h and 48 h after removal of the patches. RESULTS: The results are summarized as follows. 1. Visual scores were 0.1+/-0.3 (1%), 0.5+/-0.6 (5%) and 1.1+/-0.8 (10%) at 24 h after removal of LA, and were 0.2+/-0.4 (1%), 0.6+/-0.6 (5%) and 1.0+/-0.7 (10%) at 24 h after removal of GA. They were increased in proportion to the concentrations and there were significant differences in skin responses between the control and each concentration of the solutions. 2. E-indices were 9.1+/-2.1 (control), 8.8+/-1.8 (1%), 9.0+/-2.6 (5%) and 10.5+/-3.9 (10%) at 24 h after removal of LA, and were 9.4+/-1.8 (control), 9.3+/-2.3 (1%), 10.0+/-3.0 (5%) and 11.1+/-3.5 (10%) at 24 h after removal of GA. They were not increased in the patch areas of 1% and 5% solutions in both the LA and GA group, but were significantly increased in the patch areas of 10% solutions in both the LA and GA group. 3. TEWL values were 7.3+/-2.3 (control), 8.3+/-4.0 (1%), 9.8+/-4.5 (5%) and 16.7+/-9.1 (10%) at 24 h after removal of LA, and were 8.1+/-3.2 (control), 7.8+/-3.8 (1%), 8.6+/-3.0 (5%) and 10.9+/-4.1 (10%) at 24 h after removal of GA. They were not increased in the patch areas of 1% LA, 1% GA and 5% LA, but there were high significant differences between the controls and 10% solutions of both LA and GA. CONCLUSION: Visual scores were increased in all concentrations of AHAs tested, but the increase in E-index and TEWL values were not significant or minimal in 1% and 5% solutions of AHAs. These findings suggest that AHAs could be classified as non-corrosive irritants.

The Effect of Alpha Hydroxy Acids (Glycolic and Lactic acid) on Hairless Mouse Skin

BACKGROUND: Alpha hydroxy acid containing products are now widely used as cosmetics or skin protectives because it is believed to have a favorable effect against the aging process of skin. OBJECTIVE: The study aimed to find the effects of AHAs (glycolic acid, lactic acid) on the skin of hairless mice. METHODS: Glycolic acid (10 %, pH 3.9), lactic acid (10 %, pH 6.0) and vehicle control were applied topically to the back skin of hairless mice for two weeks. The thickness of the skin was measured by histometric analysis in addition to Masson-trichrome staining, immunohistochemical staining for TGF-beta and a Northern blot assay for pro α-l(I) collagen mRNA. RESULTS: The change of the skin after topical treatment showed decreased mean epidermal thickness in the AHAs treated group, but the thickness of the dermis increased greatly compare to the controls (glycolic acid > lactic acid > control). Staining with Massontrichrome and TGF-beta showed a relatively increased expression in the AHAs treated specimens. These effects were correlated to the increased expression of pro a-1(I) collagen mR- NA from glycolic acid treated skin. CONCLUSION: It is suggested that the favorable effects of AHAs treatment are achieved by increased dermal thickness associated with prominent collagen synthesis.