A visible cutaneous scar develops from the excess formation of immature collagen in response to an inflammatory reaction. This study examined the role of epidermal growth factor (EGF) in the formation of cutaneous scars. Twenty Crl:CD-1 (ICR) mice were used and 2 full-thickness skin wounds were made on the dorsum of each mouse. One of the wounds was treated with recombinant human EGF by local application and the other was treated with saline for control until complete healing was achieved. The EGF-treated group's wounds healed faster than the control group's. The width of the scar was smaller by 30% and the area was smaller by 26% in the EGF-treated group. Inflammatory cell numbers were significantly lower in the EGF-treated group. The expression of transforming growth factor (TGF)-beta1 in the EGF-treated group was increased. It was observed that the amount of collagen in the EGF-treated group was larger than the control group. In the EGF-treated group, the visible external scars were less noticeable than that in the control group. These results suggest that EGF can reduce cutaneous scars by suppressing inflammatory reactions, decreasing expression of TGF-beta1, and mediating the formation of collagen.
Animals ; Cicatrix/pathology/*prevention & control ; Collagen/metabolism ; Epidermal Growth Factor/*pharmacology ; Humans ; Inflammation/metabolism ; Mice ; Recombinant Proteins/*pharmacology ; Skin/drug effects/metabolism/pathology ; Wound Healing/*drug effects

OBJECTIVETo investigate the expression of apoptosis and caspase-8, cyt c in the skin of the BALB/c mice exposed to trichloroethylene (TCE).

METHODS30 BALB/c mice were divided in random into the solvent control group, 10% TCE group, 20% TCE group, 40% TCE group, 80% TCE group and 100% TCE group. Apoptotic cells were detected by TUNEL and EM. The expressions of caspase-8 and cyt c were detected with immunohistochemical method.

RESULTSEM showed that the apoptosis of cells was found in the high dosage groups. The immunohistochemical results showed that there were significant differences in the apoptosis rate and the activity of cyt c between the different dosage groups. There was the significant difference in the apoptosis rate between the 40%, 80%, 100% TCE groups the control group (P < 0.01). There was the significant difference in the expression of cyt c between the 20%, 40%, 80%, 100% TCE groups [(2.60 +/- 0.54), (3.42 +/- 0.56), (5.81 +/- 1.30) and (6.00 +/- 0.70), respectively] and the control group (P < 0.01). The expressions of caspase-8 had no significant differences (P > 0.05).

CONCLUSIONApoptosis plays an important role in trichloroethylene induced irritant injury in skin and the apoptosis may be related with the mitochondrial injury.

Animals ; Apoptosis ; drug effects ; Caspase 8 ; metabolism ; Cytochromes c ; metabolism ; Female ; Mice ; Mice, Inbred BALB C ; Mice, Nude ; Skin ; drug effects ; metabolism ; pathology ; Trichloroethylene ; toxicity

Badu Shengji San(BDSJS) is a traditional Chinese medicine (TCM) used for drawing out toxin, eliminating suppuration and promoting granulation. Toxic minerals such as arsenic and lead are the two most important components of BDSJS. Previous hypothesis indicated that according to the compatibility theory of TCM, the toxicity of the entire BDSJS was weaker than that of arsenic and lead, respectively. In the present study, SD rats with injured skin were treated with distilled water and different composition of BDSJS (complete formulations, compatible herbs, mineral medicine containing arsenic and lead, mineral medicine containing arsenic and mineral medicine containing lead) once a day for consecutive 2 weeks. Kidney coefficient and urinary beta-N-acetyl glucosidase (NAG) were used as the indicators of renal toxicity and the content of malondiadehyde (MDA), superoxide dismutase (SOD), glutathione peroxidase (GSH-PX), glutathione (GSH) and metallothionein (MT) in the renal tissue were measured. Our data showed that kidney coefficient, the severity of renal pathological lesion and MT level in the kidney of the entire BDSJS group decreased significantly compared with arsenic and lead group. Additionally, the NAG content of the entire BDSJS group had the decreased trend. The kidney CuZn-SOD level of the entire BDSJS group had the increased trend, but the MDA, GSH-PX, GSH level had no obvious difference. Our results suggested that compatible herbs in BDSJS relieved renal injury induced by arsenic and lead, and the attenuation mechanism may be related to MT and CuZn-SOD, but not to MDA, GSH-PX and GSH directly.
Animals ; Arsenic ; toxicity ; Body Weight ; drug effects ; Drugs, Chinese Herbal ; pharmacology ; toxicity ; Glutathione ; metabolism ; Glutathione Peroxidase ; metabolism ; Kidney ; drug effects ; metabolism ; pathology ; Lead ; toxicity ; Male ; Malondialdehyde ; metabolism ; Metallothionein ; metabolism ; Rats ; Rats, Sprague-Dawley ; Skin ; drug effects ; Superoxide Dismutase ; metabolism

OBJECTIVETo investigate the effects of aminoguanidine cream on the proliferation of keratinocytes (KC), content of advanced glycosylation end products (AGE) and oxidative stress in skin tissue of rats with diabetes.

METHODSStearic acid, liquid paraffin, vaseline, lanolin, isopropyl myristate fat, glycerol, 50 g/L alcohol paraben, aminoguanidine hydrochloride etc. were mixed in certain proportion to make aminoguanidine cream, and cream without aminoguanidine was used as matrix. The dorsal skin of normal rats were harvested and treated by aminoguanidine cream with dose of 5, 10 g/L, or 5 g/L together with 10 g/L azone. The transdermal effect was respectively measured at post treatment hour 2, 4, 7, 10, 12, 24. Thirty SD rats were divided into normal control (NC, n = 6), diabetes (D, n = 8), aminoguanidine cream-interfered (AI, n = 8), matrix cream-interfered groups (MI, n = 8) according to the random number table. Diabetes was reproduced by intraperitoneal injection of STZ (65 mg/kg) in rats of D, AI, and MI groups, and rats in NC group were injected with 0.05 mmol/L citrate buffer as control. One week later, dorsal skin of rats in AI and MI groups were respectively treated with 10 g/L aminoguanidine cream and matrix cream by external use for 4 weeks. AGE content was determined with fluorescence detection from skin collagen extract. KC cell cycle was detected by flow cytometry. Skin tissue specimens were obtained for determination of levels of superoxide dismutase (SOD), malondialdehyde (MDA), myeloperoxidase (MPO), and total antioxidant capacity. Data were processed with t test.

RESULTSTransdermal effect of aminoguanidine cream with dose of 10 g/L was better than that with 5 g/L or 5 g/L + 10 g/L azone cream. One rat was not induced successfully in MI group. Four weeks after model reproduction, 4 rats died in D group and 1 rat died in AI group. The AGE content in D group was obviously higher than that in NC group [(36.8 +/- 2.6), (24.6 +/- 2.7) U per milligram hydroxyproline, respectively, t = 7.2, P < 0.01], and that in AI group [(28.6 +/- 3.7) U per milligram hydroxyproline] was also lower as compared with that in D group (t = -3.9, P < 0.05). There was no significant difference in AGE content between MI [(32.2 +/- 5.2) U per milligram hydroxyproline] and D groups (t = 1.6, P > 0.05). The percentage of KC in S phase was obviously lower in D group than in NC group [(5.3 +/- 0.6)%, (7.6 +/- 0.9)%, respectively, t = 4.50, P < 0.01], while that in MI group [(9.2 +/- 1.5)%] was higher as compared with that in D group ( t = 4.90, P < 0.01). It was more higher in AI group than in D group on KC percentage in S and G2/M phase (with t value respectively 6.80, 3.17, P values all below 0.01). The oxidative stress indexes of skin tissue in D group were all higher than those in NC group, in which levels of MPO and SOD showed statistical difference (with t value respectively 4.4, 3.7, P values all below 0.05). The oxidative stress indexes were all lower in AI group than in D group, especially in SOD level (t = -1.4, P < 0.05). Levels of MAD, MPO in MI group were significantly lower than those in D group (with t value respectively 2.6, 2.9, P values all below 0.05).

CONCLUSIONSAminoguanidine cream can promote KC proliferation and appropriately reduce oxidative stress through inhibiting AGE formation to a certain extent in skin tissue of rats with diabetes. Signal use of matrix cream can also reduce oxidative stress in skin tissue of rats with diabetes.

Administration, Cutaneous ; Animals ; Cell Proliferation ; Diabetes Mellitus, Experimental ; metabolism ; pathology ; Glycation End Products, Advanced ; metabolism ; Guanidines ; administration & dosage ; pharmacology ; Keratinocytes ; drug effects ; Male ; Ointments ; administration & dosage ; pharmacology ; Oxidative Stress ; drug effects ; Rats ; Rats, Sprague-Dawley ; Skin ; drug effects ; metabolism ; pathology

OBJECTIVETo study the effects of artemether and dihydroarteannuin on the mouse model of scleroderma.

METHODSixty mice were randomly divided into 8 groups: PBS control group, model group, menstruum group (20% Tween-80, 0.4%CMC-Na), positive medicine group (penicillamine 200 mg kg(-1)), low-dose artemether group (5 mg kg(-1)), high-dose artemether group (20 mg kg(-1)), low-dose dihydroarteannuin group (5 mg kg(-1)), high-dose dihydroarteannuin group (25 mg kg(-1)). We have established a mouse model for scleroderma in Balb/c mice by subcutaneous injections of bleomycin 0.1 mL per day (200 mg L(-1) BLM) for 3 weeks. Meanwhile, the administration lasted for 4 weeks. The back skin was removed in the next day after the final administration. Treated skins and lungs were harvested and analyzed for histological sclerosis. The thickness of the skin and fibrosis degree of derma were observed and made an analysis of the contents of collagen and hydroxyproline.

RESULTCompared with the model groups, the high-dose groups markedly inhibited the thickness of derma (P<0.001), furthermore, the contents of collagen and hydroxyproline in the skin were also significantly reduced (P<0.05). Other groups of mice showed improvement on scleroderma.

CONCLUSIONOur results suggest that administration of artemether or dihydroarteannuin may be an effective approach in preventing systemic sclerosis.

Animals ; Artemisinins ; pharmacology ; Collagen ; metabolism ; Female ; Hydroxyproline ; metabolism ; Lung ; drug effects ; pathology ; Mice ; Mice, Inbred BALB C ; Scleroderma, Systemic ; metabolism ; pathology ; prevention & control ; Sesquiterpenes ; pharmacology ; Skin ; drug effects ; metabolism ; pathology

OBJECTIVETo compare the effects of Badu Shengji San (BDSJS) on rats with different injured skins.

METHODThe injured and ulcerous skin rat model was established to observe the renal injury induced by BDSJS, a mercury-containing external preparation of Chinese medicine, with urinary N-acetyl-beta-D-glucosaminidase (NAG) and retinol binding protein (RBP) as indicators of renal toxicity.

RESULTCompared to injured skin rats with the same dose, both of high and low-dose ulcerous skin groups showed obvious increase in urinary RBP and kidney coefficients, significant pathomorphological changes in renal tubules and notable epithelial cytopathic effects. In terms of NAG, the high-dose ulcerous skin group saw no significant increase, but the low-dose group recorded sharp rise.

CONCLUSIONThe renal toxicity induced by BDSJS in ulcerous skin rats was more toxic than that in injured skin ones.

Acetylglucosaminidase ; urine ; Animals ; Disease Models, Animal ; Drugs, Chinese Herbal ; pharmacology ; therapeutic use ; toxicity ; Epithelial Cells ; drug effects ; metabolism ; pathology ; Kidney Tubules ; drug effects ; metabolism ; pathology ; Male ; Mercury ; toxicity ; urine ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Retinol-Binding Proteins ; urine ; Skin ; drug effects ; injuries ; Skin Ulcer ; drug therapy ; microbiology ; Staphylococcal Skin Infections ; drug therapy

OBJECTIVETo study the effect of Shengji Huayu Recipe (SHR)on the expression of MMP-3 and TIMP-1 in the skin ulcer tissue of diabetic rats.

METHODSThe skin ulcer model was established in diabetic mice. Different compatibility proportions of SHR [the ratio of Shengji Recipe (SJR) to Huayu Recipe (HYR) = 2:1, 1:1, and 1:2, respectively] were used to intervene. The expression of MMP-3 protein in the skin ulcer of diabetic rats was detected by Western blot method,and TIMP-1 protein was detected by immunohistochemical assay.

RESULTSAt each time point, there was no statistical difference in the blood glucose level among groups (P > 0.05). But all of them increased significantly,when compared with those of the normal wound group (P < 0.01). As for the difference between after would area treatment and before would area treatment, better effect was obtained in the SHR No. 3 group and the normal ulcer group than in the diabetic ulcer model group (P < 0.05). Results of Western blot showed that the MMP-3 protein expression was higher in the SHR No. 2 group than in the SHR No.3 group (P < 0.05). Immunohistochemical results showed that TIMP-1 protein expression was lower in the SHR No. 2 group than in the SHR No. 3 group and the diabetic ulcer model group (P < 0.05). TIMP-1 protein expression was higherin the SHR No. 3 group than in the SHR No. 2 group (P < 0.01).

CONCLUSIONUsing SHR No.3 was conducive to the promotion of wound healing in early wound repair stage, and using SHR No. 2 might be conducive to inhibiting the formation of pathological scar.

Animals ; Diabetes Mellitus, Experimental ; metabolism ; Drugs, Chinese Herbal ; pharmacology ; therapeutic use ; Male ; Matrix Metalloproteinase 3 ; metabolism ; Phytotherapy ; Rats ; Rats, Sprague-Dawley ; Skin ; drug effects ; pathology ; Skin Ulcer ; drug therapy ; metabolism ; Tissue Inhibitor of Metalloproteinase-1 ; metabolism

No abstract available.
Air Pollutants/*toxicity ; Animals ; Biological Markers/metabolism ; Cell Proliferation/*drug effects ; Female ; Immunohistochemistry ; Inhalation Exposure ; Mice ; Mice, Inbred BALB C ; Nasal Mucosa/drug effects/pathology ; Ozone/*toxicity ; Proliferating Cell Nuclear Antigen/metabolism ; Respiratory Mucosa/*drug effects/metabolism/pathology ; Skin/*drug effects/metabolism/pathology

OBJECTIVETo observe the effect of single administration of mercury- containing preparation Jiuyi Dan (calcined gypsum-Shengdan 9: 1) and Shengdan on acute toxicity of rabbits, in order to assess the safety of tested drugs.

METHODThe rabbits were randomly divided into 4 groups: the calcined gypsum group (excipient control), the Jiuyi Dan group, the 90 mg Shengdan group and the 180 mg Shengdan group. After 270 mg of calcined gypsum, 300 mg of Jiuyi Dan, 90 mg of Shengdan, and 180 mg of Shengdan were used on the surface of wounds (5 cm x 5 cm) on two sides of rabbit back for 5 h, the surfaces of wound were washed by water. The bloods were taken from the rabbit hearts before and after the drug administration for 24 h, 72 h, 7 d and 14 d for determining Hg level in blood and liver & kidney function indicators (ALT, AST, CREAT, and BUN). The rabbits were dissected after the drugs treatment for 14 d, and pathological tests were made for their livers and kidneys.

RESULTCompared with the calcined gypsum group, the 90 mg Shengdan group and the 180 mg Shengdan group showed significant increase (P < 0.01 or P < 0.05), as evidenced by increase in CREAT for 24 h and 72 h and increase in BUN for 24 h and on 7 d. AST is significantly increased as well (P < 0.01) for 24 h and 72 h compared to that of the group before drug treatment. The Hg level in blood was significantly enhanced (P < 0.01) after the rabbits were administrated with drugs for 24 h to 72 h. The pathological changes in livers and kidneys of rabbits were observed in the two doses of Shengdan treatment groups.

CONCLUSIONThe Hg blood levels were increased significantly in an obvious dose-effect relationship in all drugs treatment groups. Liver & kidney function indicators were influenced by Shengdan treatment to some extent. Meanwhile, pathological changes in rabbit livers and kidneys were also caused by Shengdan, while Jiuyi Dan has no significantly effect on livers and kidneys.

Alanine Transaminase ; blood ; Animals ; Aspartate Aminotransferases ; blood ; Blood Urea Nitrogen ; Body Weight ; drug effects ; Creatinine ; blood ; Dose-Response Relationship, Drug ; Drugs, Chinese Herbal ; administration & dosage ; toxicity ; Female ; Kidney ; drug effects ; metabolism ; pathology ; Liver ; drug effects ; metabolism ; pathology ; Male ; Mercury ; blood ; metabolism ; urine ; Rabbits ; Random Allocation ; Skin ; drug effects ; injuries ; Time Factors ; Toxicity Tests, Acute

OBJECTIVETo study the effect of Jingjielianqiao Decoction in promoting leg ulcer in rabbits.

METHODSNine adult male New Zealand albino rabbits with chronic leg ulcers were randomized into 3 groups, namely group A treated with Jingjielianqiao Decoction, group B with Shengjiyuhong Decoction, and group C with normal saline. Gross observation of the wounds was carried out regularly for evaluating the changes in the ulcerous area, depth and wound surface excretion. After 3 weeks of treatment, the tissues on the edge of the ulcer were sampled and prepared for routine pathological examination, electron microscopy and immunohistochemistry for vascular endothelial growth factor (VEGF) and CD34. The number of blood vessels and their areas were also recorded.

RESULTSThe wounds showed no significant differences between the 3 groups by gross observation during the treatment, but after completion of the 3-week treatment, routine pathological examination and electron microscopy revealed significant differences between the groups. Immunohistochemistry for VEGF and CD34 yielded comparable results between groups A and B (positive control), but showed significant differences between group C and the other two groups (P<0.01).

CONCLUSIONJingjielianqiao Decoction and Shengjiyuhong Decoction can obviously promote the healing of leg ulcer in rabbits.

Animals ; Antigens, CD34 ; analysis ; Drugs, Chinese Herbal ; therapeutic use ; Immunohistochemistry ; Leg Ulcer ; drug therapy ; metabolism ; pathology ; Male ; Microscopy, Electron ; Phytotherapy ; Rabbits ; Random Allocation ; Skin ; drug effects ; pathology ; ultrastructure ; Vascular Endothelial Growth Factor A ; analysis ; Wound Healing ; drug effects