Rabbit Skin Research Articles

ACUTE CHRONICAL TOXICITY AND INTOLERANCE OF SM - COMPLEX

The researchers elaborated pharmacological complex of SM at the Chair of Morphology, Physiology and Pharmacology atSouth-UralStateAgrarianUniversity. The complex contains butafosfan, vitamins, vitamin-like substances, selected on the basis of synergistic effect on the body. The parameters of acute toxicity of the SM-complex were explored in the experiment on clinically healthy adult white mice of both genders by a single injection of the solution in the maximum permissible dose according to GOST 31926-2013. Intolerance on the skin of animals was detected in line with GOST R ISO 10993.10-2009. GOST R ISO 10993.10-99 became a guideline for evaluating SM-complex intolerance on the eye conjunctiva. Chronic toxicity was investigated on non-linear rats; the rates were divided into 4 groups of 6. The first group became a control group, the second group received the SM-complex in a therapeutic dose (255mg/kg), the third group - in a 5 -fold therapeutic dose (1275mg/kg), the fourth group - in a 10-fold dose (2550mg/kg). Pharmacological substance was applied through the probe in the form of an aqueous solution for 30 days. The researchers found out that at single oral introduction of SM-complex in the maximum possible doses it does not affect mice organism and it is referred to the 4th class of danger according to GOST 12.1.007-76. Local application in the form of applications on the skin and mucous membranes of rabbits, the complex does not have a local irritant effect. Long-term application of pharmacological composition (30 days) in high doses causes functional and morphological changes of the liver in the form of gray foci and flabbiness, as well as it increases the volume of the organ. Due to the fact that the therapeutic doses are 5 and 10 times lower than the toxic ones and the period of application does not exceed 7-14 days, the authors make a conclusion that SM-complex is safe and secure and can be used in the recommended doses.

Justification of parameters of microwave installation for separation of down from skins of rabbits in the continuous mode

Discusses the problem of reducing the operating costs of decontamination and the separation of fluff from the skins of rabbits in rabbit farms. Rabbit meat production amounted to 4.2 thousand tons, of which 70% of the total volume of Russian production falls on farms. In the Nizhny Novgorod region effectively bred rabbits breed "White Giant", which at the age of 560 days reach up to 6.8 kg, but the processing of skins is quite time-consuming. Rabbit down is widely used in the processing industry as a raw material with unsurpassed qualities for the production of knitwear, felt, cloth. The article describes the developed microwave unit with a disk conveyor with a power consumption of 6 kW, a capacity of 16 kg / h. The results of experimental studies to substantiate the complex of structural and technological parameters and modes of operation of microwave installations based on regression models, taking into account the multicriteria assessment of the technological process of separating the disinfected down raw materials from the skin with the sponge-soaked Mezdra. The annual economic effect of the use of microwave installation for collecting hair from the skins of rabbits in rabbit farms is 187 thousand rubles.

Morphological Characterization and Gene Expression Patterns for Melanin Pigmentation in Rex Rabbit.

Animal melanin has an important role in the formation of animal fur and skin, which is determined by its quantities, character, and distribution. To identify the effect of melanin on the formation of multi-colored Rex rabbits (Black, Chinchilla, Beaver, Protein cyan, Protein yellow, White), the structure of hair follicles and melanin content in multi-colored Rex rabbit skins were observed by Hematoxylin and Eosin (H&E) staining and melanin staining, respectively. The melanin granules were primarily found in the epidermis and hair follicle roots. The melanin content of skin was measured by extracting melanin from skin tissue. The results demonstrated that the melanin content was the highest in the skin of black Rex rabbit. Additionally, we measured the mRNA and protein expression levels of melanin-related key genes (MITF and TYR) in the skin of different hair color by quantitative real-time PCR and Wes assay, respectively. The results revealed that the mRNA expression levels in the skin of black Rex rabbit was highly expressed when as compared with other Rex rabbit skin (P < 0.01), and they were the lowest in the skin of white Rex rabbit. Finally, correlation analysis was conducted between melanin content and the expression levels of mRNA and protein. The results indicated a significant correlation between melanin content and the mRNA expression of MITF (P < 0.05), but it was not correlated with the mRNA expression of TYR (P > 0.05). In summary, melanin deposition has important economic value, and the coat color of fur-bearing animals is partly determined by the melanin-related genes.

Thermoreversible Gel-Loaded Amphotericin B for the Treatment of Dermal and Vaginal Candidiasis.

The present study was designed to develop a thermoreversible gel of Pluronic (P407) loaded amphotericin B (AmB-gel) for the dermal and vaginal treatment of candidiasis. P407 was used as a copolymer to exploit potential advantages related to increasing drug concentration in the tissue layer in order to provide a local effect. Parameters including internal structure, swelling, porosity, and short-term stability were determined. In addition, drug release profile and ex vivo skin and vaginal permeation studies were carried out. Antifungal efficacy was evaluated against strains of Candida spp. and atomic force microscopy (AFM) supported the results. The tolerance of AmB-gel was studied by evaluating biomechanical properties of skin and determining the irritation level in scarified rabbit skin supported by histological analysis. Results confirmed the development of a thermoreversible AmB-gel with high porosity exhibiting Newtonian behavior at 4 °C and pseudoplasticity at 32 °C as well as optimal stability for at least 90 days. The Amb-gel provided a sustained drug release following a Boltzmann sigmoidal model. Non permeation was observed in skin and vaginal mucosa, showing a high retained amount of AmB of 960.0 and 737.3 µg/g/cm2, respectively. In vitro antifungal efficacy showed that AmB-gel was more effective than Free-AmB in inhibiting strains of Candida spp. and these results were corroborated by AFM. Finally, tolerance studies showed that its application did not induce skin irritation nor alter its biophysical properties. Together, these results confirmed that AmB-gel could be proposed as a promising candidate for the clinical status in the treatment of skin and vaginal candidiasis.

The Use of Antifibrotic Recombinant nAG Protein in a Rat Liver Fibrosis Model.

Objectives The “nAG” protein is the key protein mediating the regeneration of amputated limbs in salamanders. The senior author (MMA) developed the original hypothesis that since “nAG” is a “regenerative” protein, it must be also an “antifibrotic' protein. The antifibrotic properties were later confirmed in a rabbit skin hypertrophic scar model as well as in a rat spinal cord injury model. The aim of this study is to evaluate the potential therapeutic properties of the nAG protein in a rat liver fibrosis model. Methodology Liver fibrosis was induced using intraperitoneal injections of carbon tetrachloride (CCL4). A total of 45 rats were divided equally into 3 groups: Group I (the control group) received normal saline injections for 8 weeks, Group II received CCL4 for 8 weeks, and Group III received CCL4 and nAG for 8 weeks. At the end of the experiment, the serum levels of 6 proteins (hyaluronic acid, PDGF-AB, TIMP-1, laminin, procollagen III N-terminal peptide, and collagen IV-alpha 1 chain) were measured. Liver biopsies were also taken and the stages of live fibrosis were assessed histologically. Results The CCL4 treatment resulted in a significant increase in the serum levels of all 6 measured proteins. The nAG treatment significantly reduced these high levels. The degree of liver fibrosis was also significantly reduced in the CCL4/nAG group compared to the CCL4 group. Conclusions nAG treatment was able to significantly reduce the serum levels of several protein markers of liver fibrosis and also significantly reduced the histological degree of liver fibrosis.

Outbreak of Vaccinia Virus Infection from Occupational Exposure, China, 2017.

Human infections with vaccinia virus (VACV), mostly from laboratory accidents or contact with infected animals, have occurred since smallpox was eradicated in 1980. No recent cases have been reported in China. We report on an outbreak of VACV from occupational exposure to rabbit skins inoculated with VACV.

A novel wound dressing material with prolonged action

The development and creation of non-toxic dressing materials exhibiting pronounced antimicrobial effect and accelerating wound-healing process without increasing pathogenic microorganisms drug resistance is an actual task of modern medicine. Aim. Evaluation of toxicological characteristics of a dressing material containing 6 % and 9 % active chlorine in a single application on the skin as well as the study of dressing material effect on the epithelization rate of the uninfected wound surface and determination of its antimicrobial and wound healing activity in vivo on a model of S. aureus ATCC 6538-infected wound. Materials and methods . An experimental study of the dressings with immobilized polymeric N-chlorosulfonamide sodium and N,N-dichlorosulfonamide was performed to evaluate the safety in use and pharmacological activity in vivo . Evaluation of the dressing material toxicological characteristics in a single application on the skin was carried out on laboratory rats and rabbits according to the generally accepted method, the wound healing effect was studied using the test by L. N. Popova and antimicrobial activity in vivo - on a model of wound infected by the insertion of a 24-hour culture of S. aureus ATCC 6538 contaminated silk thread through the skin. Results . Acute toxicity pharmacological studies of material test-samples containing 6 % and 9 % active chlorine in a single application on the skin of rats and rabbits found that these applications did not lead to deaths, as well as changes in their behavioral pattern, consumption of feed and water. The epithelization rate of uninfected wound surface in application of dressings containing both sodium N-chlorosulfonamide and N, N-dichlorosulfonamide was significantly, on average 1.5 times, faster at the end of the observational period (day 14) in comparison with the control group animals. According to the data obtained, the application of dressings containing sodium N-chlorosulfonamide on the 24-hour culture of S. aureus ATCC 6538 infected wound significantly reduced the intensity of the inflammatory process local manifestations and 4–10 times decreased the number of pathogenic staphylococci under bandages on day 8 of observation. Conclusions . Thus, a single application of native materials on the animal skin does not cause a lethal outcome. Skin application of polymeric materials on uninfected wounds stimulates the processes of natural reparation, and decreases the number of pathogenic microorganisms in wound fluid as well as shortens the healing time in staphylococcus-infected wounds.

Neuroprotective effects of neurotropin in a mouse model of hypoxic-ischemic brain injury.

Ischemic-hypoxic insult leads to detrimental effects on multiple organs. The brain is especially vulnerable, and it is hard to regenerate once damaged. Currently, therapeutic options are very limited. Previous studies have reported neuroprotective effects of neurotropin, a non-protein extract derived from the inflamed skin of rabbits inoculated with vaccinia virus, using a murine model of peripheral nerve injury and cultured cell lines. However, whether neurotropin might have protective effects against brain injuries remains unclear. We, therefore, investigated the neuroprotective effect of neurotropin and possible underlying mechanisms, using a mouse model of hypoxic-ischemic brain injury. Hypoxic-ischemic brain injury was induced via a combination of the left common carotid artery occlusion and exposure to hypoxic environment (8% oxygen) in adult male C57BL/6 mice. Immediately following induction of hypoxia-ischemia, mice received either saline or 2.4 units of neurotropin. The survival rate, neurological function, infarct volume, and expression of inflammatory cytokines were evaluated. Compared to the control group, the neurotropin group exhibited a significantly higher survival rate (100% vs. 62.5%, p < 0.05) and lower neurological deficit scores (1; 0-2 vs. 3; 0-5, median; range, p < 0.05) after the hypoxic-ischemic insult. The administration of neurotropin also reduced infarct volume (18.3 ± 5.1% vs. 38.3 ± 7.2%, p < 0.05) and mRNA expression of pro-inflammatory cytokines. The post-treatment with neurotropin improved survival and neurological outcomes after hypoxic-ischemic insult. Our results indicate that neurotropin has neuroprotective effects against hypoxic-ischemic brain injury by suppressing pro-inflammatory cytokines.

Role of mechanical and thermal damage in pericapsular inflammatory response to injectable silicone in a rabbit model.

Silicone is used widely for tissue augmentation in humans. However, late complications, such as delayed inflammation and capsular contracture, remain uncharacterized, despite their importance. In the present study, we aimed to determine whether mechanical and thermal damage induce capsular inflammation around a foreign body, and elucidate the biological mechanism underlying this phenomenon. We injected silicone into the subcutaneous layer of the skin of New Zealand white rabbits. The rabbits were divided into two groups: the control group received no treatment; in the experimental group, external force was applied near the injection silicone using high-intensity focused ultrasound (HIFU). Tissues near the injected silicone were harvested from both groups on Days 4, 7, and 30 after HIFU treatment for comparative analysis. Visual and histological examinations showed clearly increased inflammation in the experimental group compared with that in the control group. Furthermore, capsular tissue from the experimental group displayed markedly increased collagen production. Immunofluorescence revealed marked activation of macrophages in the early stages of inflammation (Days 4 and 7 after HIFU treatment), which decreased on Day 30. Assessment of cytokine activation showed significantly increased expression of heat shock protein (HSP)27, HSP60, HSP70, toll-like receptor (TLR)2, TLR4, and interleukin-8 in the experimental group. The expression of transforming growth factor-β1 did not increase significantly in the experimental group. In conclusion, damage to tissues around the injected silicone induced capsular inflammation. Macrophages and damage-associated molecular pattern molecules were involved in the early stages of inflammation. HSP release activated TLRs, which subsequently activated innate immunity and induced the inflammatory response.

Noncontact photoacoustic angiography with an air-coupled ultrasonic transducer for evaluation of burn injury

In vivo identification of viable and thermally coagulated blood in a burn wound can be used to profile the type, extent, and site of the burn, thus assisting the removal of necrotic tissue in preparation for skin grafts. Recently, intensive research on photoacoustic imaging (PAI) has been conducted to evaluate burn injury. However, most PAI systems usually take the approach of direct physical contact of an acoustic detector or an impedance matching medium with the vulnerable burned skin, which exposes significant limitations on the diagnosis of burn injuries. Here, we present a noncontact PAI system, based on a custom designed air-coupled ultrasonic transducer, enabling in vivo noncontact vasculature to be imaged without contrast agents. Using the natural difference in light absorption between coagulated and non-coagulated blood at the wavelength of 532 nm, this PAI system possesses an immanent advantage to discriminate viable and thermally coagulated blood in burned tissues. Phantom experiments and burned rabbit's skin imaging have been implemented to demonstrate that the noncontact PAI technique could be valuable in the adjuvant diagnosis and observation of burns.

Can an inflammatory reaction in the meninges, caused by spinal puncture through tattooed skin, evolve into adhesive arachnoiditis? An experimental model in rabbits

Background and objectivesAs the number of people with tattoos has been increasing, anesthesiologists are more and more faced with the decision to perform a neuraxial blockage through tattooed skin. In...

Analyses of histological and transcriptome differences in the skin of short-hair and long-hair rabbits

BackgroundHair fibre length is an important economic trait of rabbits in fur production. However, molecular mechanisms regulating rabbit hair growth have remained elusive.ResultsHere we aimed to characterise the skin traits and gene expression profiles of short-hair and long-hair rabbits by histological and transcriptome analyses. Haematoxylin-eosin staining was performed to observe the histological structure of the skin of short-hair and long-hair rabbits. Compared to that in short-hair rabbits, a significantly longer anagen phase was observed in long-hair rabbits. In addition, by RNA sequencing, we identified 951 genes that were expressed at significantly different levels in the skin of short-hair and long-hair rabbits. Nine significantly differentially expressed genes were validated by quantitative real-time polymerase chain reaction. A gene ontology analysis revealed that epidermis development, hair follicle development, and lipid metabolic process were significantly enriched. Further, we identified potential functional genes regulating follicle development, lipid metabolic, and apoptosis as well as important pathways including extracellular matrix-receptor interaction and basal cell carcinoma pathway.ConclusionsThe present study provides transcriptome evidence for the differences in hair growth between short-hair and long-hair rabbits and reveals that lipid metabolism and apoptosis might constitute major factors contributing to hair length.

Evaluation of Skin Irritation and Acute and Subacute Oral Toxicity of Lavandula angustifolia Essential Oils in Rabbit and Mice.

Lavandula angustifolia is used in traditional and folk medicines of Ankober District, North Central Ethiopia, for the treatment of several livestock and human disorders. This toxicity study aimed to investigate L. angustifolia essential oil oral toxicity in mice and skin irritation in rabbit. L. angustifolia essential oil was analyzed using gas chromatography-mass spectrometry methods and showed predominance of Eucalyptol (52.36%), Camphor (11.91%), gamma-terpinene (8.775%) and endoborneol (7.585%). Limit test at 2000 mg/kg dose was used for L. angustifolia essential oil acute toxicity test and revealed LD50 value was higher than 2000 mg/kg. For subacute toxicity study 2000mg/kg was given orally to each mouse for 21 days. The result demonstrated no significant changes (p > 0.05) in the body weights, and biochemical parameters, gross abnormalities, water, and food intake were observed. No macroscopic changes were seen in the histopathology analysis of kidneys and livers. For skin irritation test shaved rabbit skin was treated with 10% ointment formulation. Ointment of L. angustifolia oil did not affect mice skin. Generally, this toxicity study demonstrated that L. angustifolia essential oil is nontoxic.

Ischemia postconditioning protects dermal microvascular endothelial cells of rabbit epigastric skin flaps against apoptosis via adenosine A2a receptors

Background: It has been shown that endogenous adenosine-induced by ischemia postconditioning attenuates apoptosis in recent studies; however, they focus only on parenchymal cells. The detailed mechanism has not been clearly clarified in any research and the subtype of adenosine receptors involved remains unknown. In our study, dermal microvascular endothelial cells (DMECs) are used to explore the role of adenosine A2a receptor in the anti-apoptotic effects of ischemic postconditioning.Material and methods: The epigastric skin flaps of rabbits were elevated. After 4 h of ischemia, the flaps were either abruptly reperfused or postconditioned by six cycles of brief reperfusion (15s) and re-ischemia (15s). Adenosine A2a receptor agonist (CGS-21680) and antagonist (ZM-241385) were used separately in other groups. The apoptosis-related proteins and adenosine A2a receptors were determined by immunohistochemical staining. Then apoptosis index was calculated by TUNEL.Results: Ischemia/reperfusion caused severe damages in DMECs of flaps as demonstrated by an increase in apoptosis index and an increase in expressions of apoptosis-related proteins, which can be significantly attenuated by IPC treatment or exposure to a selective adenosine A2a receptor agonist (all p values <.05). Meanwhile, the anti-apoptosis effects of IPC can be blocked by a selective adenosine A2a receptor antagonist. Statistical analysis revealed that the increase of apoptosis index closely correlated inversely with the relative increase of adenosine A2a receptors (p < .0001).Conclusions: Ischemia postconditioning protects DMECs of rabbit skin flap against apoptosis via activation of adenosine A2a receptors.

Bioinspired baroplastic glycosaminoglycan sealants for soft tissues

We describe biomimetic adhesives inspired by the marine glues fabricated by the sandcastle worm. The formation of stable polyelectrolyte complexes between poly-L-lysine (PLL) and glycosaminoglycans (GAGs) with different sulfation degree – heparin (HEP), chondroitin sulfate (CS) and hyaluronic acid (HA) – is optimized by zeta-potential titrations. These PLL/GAG complexes are transformed into compact polyelectrolyte complexes (coPECs) with controlled water contents and densities via baroplastic processing. Rotational shear tests demonstrate that coPECs containing sulfated GAGs (HEP or CS) have solid-like properties, whereas HA-based complexes form highly hydrated viscous-like networks. The adhesiveness of the generated coPECs (normalized lap shear strength) is tested in dry and wet states using polystyrene and rabbit skin, respectively. In dry state, the adhesives exhibit lap shear strengths in the order of hundreds of kPa, with coPLL/HEP and coPLL/CS being about 1.5 times stronger than coPLL/HA. In wet state, all coPECs seal rabbit skin and recover over 60% of the elongation capacity of intact skin with coPLL/HA providing the sturdiest adhesion (∼85% elongation recovery). We demonstrate that this is due to the higher water fraction that improves the bonding between the wet specimens, showcasing the potential superior mechanical recovery on injured tissues. Statement of SignificanceThe development of medical sealants with sufficient adhesive strength in the presence of water and moist remains a huge challenge. We present glycosaminoglycans (GAGs) as biomaterials for the assembly of baroplastics with strong adhesive strength to soft tissues at physiological conditions. Baroplastics with tacky properties were generated by a mild assembly process based on polyelectrolyte complexation and compaction. These materials behave as versatile sealants: their adhesiveness can be adjusted to either dry or wet specimens because of the different sulfation degree of GAGs. These sealants were noncytotoxic towards L929 cells and allowed the damaged skin to recover a great deal of its native elasticity: they preserved the J-shaped stress/strain mechanical response that is typical of biological soft tissues.

Structure of Hyla rabbit skin gelatin as affected by microwave-assisted extraction

ABSTRACT In this study, we investigated the effect of microwave-assisted extraction (MAE) on the yield, structure, and properties of rabbit skin gelatin. Compared to water bath extraction gelatin, short-term (5–30 min) MAE gelatin had better gel properties, which formed gels at a slower rate due to destruction of more hydrogen bonds, but had more powerful triple helix-like structures after a sufficiently long maturity (16–18 h) since more high-molecular-weight subunits were retained. Scanning electron microscope showed that MAE could form numerous holes on the surface of gelatin. This study will be of great significance for high efficiency of gelatin extraction.

Permeation-enhancing effects and mechanisms of O-acylterpineol on isosorbide dinitrate: mechanistic insights based on ATR-FTIR spectroscopy, molecular modeling, and CLSM images

The present study aimed to evaluate the penetration activity of O-acylterpineol derivatives both in vitro and in vivo, and to investigate the enhancing mechanism of O-acylterpineol derivatives which were synthesized by α-terpineol and fatty acid. The promoting activities on the isosorbide dinitrate patch were tested across full thickness rabbit skin both in vitro and in vivo. In order to elucidate the permeation mechanism, attenuated total reflection Fourier transform infrared spectroscopy, molecular modeling, and confocal laser scanning microscopy were introduced to investigate the regulation of enhancers in the skin permeability and biophysical properties. With in vitro cytotoxicity test and in vivo erythema model, the skin irritation of enhancers was also evaluated. Permeation studies showed 2-(4-methylcyclohex-3-en-l-yl) propan-2-yl tetradecanoate produced the obvious enhancement activity for ISDN both in vitro and in vivo from patches. These results were supported by ATR-FTIR, molecular modeling, and CLSM studies which revealed that O-acylterpineol could decrease the order of the alkyl chains in the skin lipids. Additionally, it was found that TER-C14 produced a relatively low skin irritation, compared with the TER which was assumed to be a safe compound. The present research suggested that some newly designed acylterpineol derivatives are shown to be suitable permeation enhancers for transdermal drug delivery, and the chain length of C14 seem to be safe and more favorable for the penetration of ISDN from DIA patches.

Papillomavirus can be transmitted through the blood and produce infections in blood recipients: Evidence from two animal models

ABSTRACT Human papillomaviruses (HPV) contribute to most cervical cancers and are considered to be sexually transmitted. However, papillomaviruses are often found in cancers of internal organs, including the stomach, raising the question as to how the viruses gain access to these sites. A possible connection between blood transfusion and HPV-associated disease has not received much attention. Here we show, in rabbit and mouse models, that blood infected with papillomavirus yields infections at permissive sites with detectable viral DNA, RNA transcripts, and protein products. The rabbit skin tumours induced via blood infection displayed decreased expression of SLN, TAC1, MYH8, PGAM2, and APOBEC2 and increased expression of SDRC7, KRT16, S100A9, IL36G, and FABP9, as seen in tumours induced by local infections. Furthermore, we demonstrate that blood from infected mice can transmit the infection to uninfected animals. Finally, we demonstrate the presence of papillomavirus infections and virus-induced hyperplasia in the stomach tissues of animals infected via the blood. These results indicate that blood transmission could be another route for papillomavirus infection, implying that the human blood supply, which is not screened for papillomaviruses, could be a potential source of HPV infection as well as subsequent cancers in tissues not normally associated with the viruses.

Phytochemical analysis and evaluation of skin irritation, acute and sub-acute toxicity of Cymbopogon citratus essential oil in mice and rabbits.

Cymbopogon citratus has been used by the local people in Ankober district, northern Ethiopia, as traditional medicine to treat various ailments. Its essential oil has been shown to have antibacterial, antifungal, antiprotozoal, anti-carcinogenic, anti-inflammatory and antioxidant activities amongst others. This study was conducted to determine skin irritation, acute and subacute toxicity of C. citratus essential oil in mice and rabbits. The essential oil was analyzed using GC-MS. The essential oil at dose of 2000 mg/kg body weight was administered to mice for 21 consecutive days. The mice mortality, behavioral change, injury and other signs of illness were recorded once daily. Biochemical parameters were evaluated. Liver and kidney were taken after sacrifice for gross findings and histological analyses. 10 % ointment formulation of C. citratus oils was applied on the rabbit skin to determine skin irritation effects. The result revealed, the presence of citral (71.297%), myrcene (19.034%), 4, 5-epoxycarene (2.780%), linalool (1.713%), ((S)-cis-verbenol (1.110 %), linalool (1.713 %), ((S)-cis-verbenol (1.110 %) and undecan-2-one (1.001 %) in the C. citratus essential oil. There was no significant difference (p > 0.05) in the body weights, gross abnormalities of the organs and biochemical parameters compared to the control. No histopathological changes were detected in the organs tested. 10 % ointment formulation of C. citratus oils did not cause skin irritation. Analysis of results leads to the conclusion that Ethiopian C. citratus essential oil may be considered as relatively safe and non-toxic.

3T3-L1 지방전구세포와 고지방 식이로 유도된 비만 HR-1 마우스 피부에 도포한 한약 추출 복합물의 항비만 효과 및 안전성 평가

The aim of this study was to investigate whether a novel formulation of an herbal extracts has an inhibitory effect on obesity. To determine its anti-obesity effects, we performed anti-obesity-related experiments in vitro and in vivo . Thus, our present study was carried out to evaluate the anti-obesity effect of herbal extracts using a high fat diet (HFD)-induced obese mouse model and 3T3-L1 adipose cells. The effects of each herbal extracts on lipid accumulation in 3T3-L1 cells were examined using Oil Red O staining. Results showed that treatment with each herbal extracts at 10~100 μg/㎖ had no effect on cell morphology and viability. Without evidence of toxicity, herbal extracts treatment decreased lipid accumulation compared with the untreated adipocytes controls as shown by the lower absorbance of Oil Red O stain. Futhermore, compared with control-differentiated mature adipocytes, each herbal extracts significantly inhibited lipid accumulation in mature 3T3-L1 adipocytes. In the HFD-fed obese mice, body weight, liver weight and white adipose tissue weights were significantly reduced by mixture of herbal extracts administration in mouse skin. Futhermore, we found that mixture of herbal extracts administration suppressed serum triglyceride (TG), and total cholesterol (TCHO) in HFD-induced obese mouse model. The mixture of herbal extracts of permeability was estimated by measuring the transepithelial electrical resistance (TEER) value in pig skin. The optimized formulations of herbal extracts (Test 3 formulation) showed skin permeation. However, test 1 formulation containing essential oil as enhancer showed maximum skin permeation. After confirming the enhanced skin permeability, in vivo studies were performed to assess whether skin irritation potential on the basis of a primary irritation index (PII) in rabbit skin. Reactions were scored for erythema/edema reactions at 24 h, 48 h and 72 h post-application. It was concluded that the test 1 formulation was not irritation (PII = 0). The present study suggests that the test 1 formulation might be of therapeutic interest with respect to the treatment of obesity.