Cutaneous and Ocular Toxicology最新文献

Objective: Ultraviolet-B (UVB) radiation is an important factor in causing skin damage. The study is to explore whether 1,25-Dihydroxvitamin D3(1,25(OH)₂D₃) will attenuate the damage of human immortalised keratinocytes (HaCaT) cells caused by UVB and relevant underlying mechanisms.

Methods: CCK-8 was employed to determine the UVB irradiation intensity and 1,25(OH)₂D₃ concentration. Western blot was used to detect the expression of NF-κB, Caspase9, Caspase3, Bax, Bcl2, FADD, CytC, Beclin-1; Flowcytometry was applied to measure the production of ROS.

Results: The concentration of 1,25(OH)₂D₃ used in the study was 100 nM and the UVB irradiation intensity was 20 mJ/cm². Compared with the HaCaT cells irradiated with UVB, the HaCaT cells that were pre-treated with 1,25(OH)₂D₃ had lower production of ROS, lower expression of NF-κB, Caspase9, Caspase3, Bax, FADD, CytC and Beclin-1(P < 0.05).

Conclusion: 1,25(OH)₂D₃ could inhibit the development of oxidative stress and apoptosis in HaCaTs triggered by UVB. This inhibition might be achieved through the suppression of mitochondria-modulated apoptosis and autophagy. Vitamin D may be a potential UVB protective component.

Purpose: The purpose of the current study was to evaluate the effect of Triticum vulgare (TVE) alone or combined with therapeutic ultrasound (TUS) on wound healing in a diabetic rat model.

Materials and methods: A total of 72 male Wistar rats were randomly divided into four groups: Group Control, wounded rats without treatment; Group TUS, wounded rats with TUS application; Group TVE, wounded rats treated with TVE; and Group TVE + TUS, wounded rats treated with TVE + TUS. Wound healing was assessed using wound area calculation and thermographic, biochemical, histopathologic, immunohistochemical, and immunofluorescence analyses on post-wounding days 7, 14, and 21.

Results: On day 21, the wound surface area was significantly decreased in Group TVE + TUS (0.18 ± 0.07 cm²) compared to the other groups (p < 0.001). A significant increase in wound area temperature was recorded on days 7, 14, and 21 in all groups compared to day 0 (p < 0.001). On day 21, Group TVE + TUS (35.4 ± 0.2 °C) had the most significantly highest wound area temperature compared to the other groups (p < 0.001). The highest histopathological scores were recorded in Group TVE + TUS on days 7, 14, and 21 (p = 0.04). The highest vascular endothelial growth factor expression was observed in Group TVE + TUS (82.53 ± 1.98) on day 7 (p = 0.03).

Conclusion: In conclusion, treatment with a combination of TVE and TUS effectively enhanced wound healing in diabetic rats compared with other treatment groups.

Purpose: This article aims to gather and review the available knowledge on several implications of smoking and environmental tobacco smoke (ETS) exposure in ocular disorders and provides pathomechanistic insights where applicable.

Materials and methods: PubMed and Scopus databases were searched for relevant studies on the association of smoking and ETS exposure with various ocular disorders. Studies with different evidence levels, e.g., in-vivo, case-control, cohort, and meta-analysis, were included.

Results: Smoking is an established, modifiable risk factor in several ocular diseases, including cataract, age-related macular degeneration, and Graves' ophthalmopathy; smokers are subject to more severe disease courses and less favorable treatment outcomes. Uveitis is twice as likely in smokers; smoking may also delay its resolution. Smoking and ETS exposure are major risk factors for diseases of other organs, with associated ocular complications as well, such as diabetes mellitus. ETS exposure is also associated with ocular surface pathologies, including dry eye syndrome. In children, early-life ETS exposure and maternal smoking during pregnancy are strongly associated with refractive errors and strabismus. Currently, available data on potential risks attributable to ETS exposure regarding ocular diseases are scarce and, in some instances, controversial.

Conclusion: In addition to smoking, ETS exposure is also a significant public health concern with possible links to several ocular diseases. However, the level of education of at-risk populations in this regard does not match the strength of the evidence.

Purpose: Air pollution is a public health problem caused by predatory human activities and the indiscriminate burning of fossil fuels that liberate particulate matter (PM) into the atmosphere. Vanadium (V) adheres to them and reaches the bloodstream and different organs such as the eye when inhaled. Another way to reach the eye is by direct contact, and the cornea is the first layer exposed. Ciliary neurotrophic factor (CNTF) is secreted by the corneal nerves and some of its functions include self-renewal maintenance and wound healing by the activation of STAT3. Previous reports from our group indicate the activation of STAT3 after the inhalation of V, adhered to PM.

Objective: To analyse the effect of V inhalation in the expression of CNTF. Method: CD-1 male mice were exposed for 4 and 8 weeks to V inhalation. The eyes were removed, and the corneas were processed for immunohistochemistry for CNTF and analysed by densitometry. The same slides were used to evaluate histological modifications and to measure the corneas' anterior epithelial and endothelial thickness.

Results: A decrease in CNTF expression in the anterior epithelium in the 8th week, as well as an increase in the endothelial and corneal thickness and disarray of all the layers of the anterior epithelium.

Conclusion: V inhalation disturbs the architecture of the cornea and modifies the presence of CNTF which might modify the renewal of the corneas after exposure to PM air pollution.

Introduction: Melanoma is known as an aggressive and highly lethal cancer. The poor prognosis and resistance to treatment are characteristics of melanoma. In melanoma cells, apoptosis signaling which relies heavily on the acute activity of mitochondria and reactive oxygen species (ROS) formation is suppressed. Studies have shown that compounds isolated from marine herbs and animals, have been shown to have cytotoxic consequences on cancerous cells in prior research. This study was designed to evaluate the apoptotic effect of methanolic extract of Persian Gulf shell-less marine mollusc (Peronia peronii) on skin mitochondria isolated from animal model of melanoma.

Purpose: Melanoma mitochondria obtained from skin of melanoma animal model are studied in this research to see whether extracts from Persian Gulf shell-less marine mollusc (Peronia peronii), has a cytotoxic impact on them.

Material and method: In this study, the mitochondria were isolated from melanoma cells via differential centrifugation were treated with various concentrations (650, 1300 and 2600 µg/ml) of methanolic extract of Peronia peronii. Then MTT(3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) viability assay, Reactive oxygen species (ROS) determination, Mitochondrial Membrane Potential (MMP) decline assay, mitochondrial swelling and cytochrome c release determination were performed. Flow cytometry assay of % apoptotic vs necrotic phenotypes was also performed on extract treated melanoma cells.

Results: The results of MTT assay showed that different concentrations of Peronia peronii extract significantly (P < 0.05) decreased the SDH activity in cancerous skin mitochondria with the IC50(1300 μg/ml). The ROS results also showed that all concentrations of Peronia peronii extracts significantly increased ROS production, MMP decline and the release of cytochrome c in cancer groups mitochondria. The swelling of mitochondria was significantly increased compared to the control group. In addition, the results of apoptosis assay showed that addition of root extract of Peronia peronii on melanoma cells increased apoptosis, while it had no effect on control non tumour cells.

Discussion and conclusion: Based on these results, the presence of potentially bioactive compounds in Peronia peronii make this Persian Gulf coastal herb a strong candidate for further molecular studies and clinical research in the field of melanoma cancer therapy.

Purpose: Ribociclib is a CDK4/6 inhibitor approved for the treatment of breast cancer; it inhibits the activity of CDK4/6 by competitively binding to adenosine 5'-triphosphate (ATP) binding sites. Although generally well-tolerated, ribociclib has been connected to a number of serious dermatologic complications. This study explored the effects of ATP on ribociclib-induced skin damage.

Materials and methods: Using a rat model, ATP 25 mg/kg was injected intraperitoneally in the ATP + Ribociclib (ATR) group (n = 6). Distilled water as solvent was applied to the healthy control (HC) group (n = 6) and ribociclib (RCB) group (n = 6). One hour after ATP and solvent administration, ribociclib (200 mg/kg) suspension prepared in distilled water was administered to the stomach by gavage (ATR and RCB groups). This was repeated once a day for 15 d. After that period, biochemical markers were studied in the skin tissues and histopathological evaluations were conducted.

Results: In the histopathological evaluation of the RCB group, dermal necrosis, degeneration in hair follicles, and pycnosis in keratinocytes were observed. Only mild degeneration was observed in the ATR group; the HC group had a normal histological appearance. The malondialdehyde (MDA) values were significantly higher and the superoxide dismutase (SOD), catalase (CAT), and total glutathione (tGSH) levels were significantly lower in the RCB group in comparison to the HC group (p < .001). ATP reduced the ribociclib-induced increases in the MDA values and decreased the SOD, CAT, and tGSH levels in the ATR group (p < .001).

Conclusion: ATP may be useful in the treatment of ribociclib-induced skin damage.

Purpose: OptiSafe^TM (OS) is a shelf stable, nonanimal test for ocular irritation. A recent database search found that half of the OS false positive (FP) materials were associated with reactive oxygen chemistries but were not eye irritants in vivo (based on historical rabbit studies by other groups). We hypothesized that naturally occurring tear antioxidants protect the eye from reactive chemistries in vivo and that specific tear chemistries might help explain why some materials are FP for nonanimal tests but are reported as nonirritants in the live animal. To test this hypothesis, a prior study evaluated tear antioxidants and found that the tear antioxidant ascorbic acid, added at human physiological tear levels to the OS test, specifically reduced the measured values for these FPs but did not reduce the true-positive rate. Based on these findings, the OS test method was further optimized. The purpose of the current study was to comprehensively evaluate the performance of the further optimized test method for detection of ocular irritants.

Materials and methods: The OS test measures chemically induced damage to macromolecules and relates these measured values to ocular irritancy. To improve the performance of OS, we made updates to the material to be tested physiochemical handling procedures, prediction model, and test method to include tear-level concentrations of ascorbic acid. We then retested the 78 chemicals from the prior OS-coded validation study in triplicate and compared the accuracy of the 'nonirritant versus irritant' prediction for the further optimized method with the prior results.

Results: We report that for the detection of 'nonirritant' versus 'irritant' (GHS NC versus categories 2B/A and 1) test substances, the further optimized OS test with ascorbic acid compared with the original version has a FP rate that is reduced from 40.0 to 22.2%, the false-negative (FN) rate remains at 0.0%, and the accuracy improved from 80.3% to 89.2%.

Conclusion: A comparison to OECD-adopted tests demonstrates that the further optimized OS test, like the original method, has a higher accuracy and lower FN rate for the detection of 'nonirritants' versus 'irritants' (GHS Category NC versus 2B/A and 1) than the other eye irritation tests (BCOP, EpiOcular^TM Eye Irritation Test, ICE, Ocular Irritection^®, and STE).

Background: Literature on the effects of second-generation H1-antihistamines on angiogenesis is limited.

Objectives: To investigate the effects of cetirizine, desloratadine, and rupatadine (second-generation H1-antihistamines commonly used in dermatology clinics) on angiogenesis in an in vivo chick chorioallantoic membrane (CAM) model.

Methods: The study was approved by the local ethics committee on animal experimentation. Forty fertilized specific pathogen free eggs were incubated and kept under appropriate temperature and humidity control. Drug solutions were prepared in identical concentrations by dissolving powders in phosphate-buffered saline (PBS). On the third day of the incubation, a small window was opened on the CAM and 0.1 mL desloratadine (1.5 μg/0.1 mL) in the first group, 0.1 mL cetirizine (1.5 μg/0.1 mL) in the second group, 0.1 mL rupatadine in the third group (1.5 μg/0.1 mL), and PBS (0.1 mL) in the fourth group were administered by injection. On the eighth day of incubation, the vascular structures of the CAMs were macroscopically examined and standard digital photographs were taken. The digital images were analyzed and data including mean vessel density, thickness, and number were compared between groups. p < 0.05 was considered statistically significant.

Results: Vessel densities were similar in the desloratadine, cetirizine, and control groups, whereas they were significantly less in the rupatadine group (p = 0.01). Furthermore, the rupatadine group had significantly lower vessel thickness and number compared with the other groups (p < 0.05 for both).

Conclusions: Rupatadine showed anti-angiogenic effects in the chick CAM model, compared with desloratadine and cetirizine. The anti-angiogenic effect of rupatadine could be due to its platelet-activating factor (PAF) receptor inhibition. Thus, rupatadine could be a treatment agent in pathological processes in which angiogenesis is responsible. Further studies with larger series are needed to clarify this potential.

Purpose: To evaluate dry eye parameters, corneal topographic features, corneal densitometric changes, and anterior segment parameters in patients receiving systemic isotretinoin treatment.

Methods: This prospective cross-sectional study included 66 eyes of 33 patients who were started on oral isotretinoin therapy for severe acne vulgaris. All patients were evaluated in terms of ocular surface tests such as tear break-up time (TBUT) and Schirmer-1 and were asked to fill in the ocular surface disease index (OSDI) questionnaire. Corneal densitometric and topographic measurements were obtained using the Scheimpflug imaging system.

Results: The mean age of the patients was 19.9 ± 1.6 years, and 21 (63.6%) of the participants were female. The mean OSDI score was significantly higher in the third month than before treatment (20.05 ± 19.38, vs. 26.96 ± 22.94, p = 0.00, respectively). The mean values of the TBUT test were significantly lower in the third month than before treatment (9.06 ± 4.40 sec, vs. 10.71 ± 4.61 sec, p = 0.02, respectively). Mean scores of the Schirmer 1 test showed no statistically significant difference between before treatment and the third month (16.08 ± 8.40 mm, vs. 16.08 ± 8.50 mm, p = 1, respectively). There was no statistically significant difference between before treatment and the third month in the majority of the densitometry measurements in concentric zones. However, the difference tended to be significant between the groups concerning posterior zone 0-2 mm (11.01 ± 0.85 GSU vs. 10.62 ± 0.89 GSU, p = 0.006). The RMS LOAs (front), RMS Total (Total), RMS LOAs Total (Total), RMS HOAs Total (Total), K_max, CCT, and CoV values were significantly higher in the third month than before treatment (p < 0.05 for all).

Conclusions: The dermatology specialists should be aware of the ocular complications of systemic isotretinoin therapy. Therefore, a complete ophthalmologic examination for the prompt apprehension and management of ocular involvement is essential in patients under isotretinoin therapy to increase ocular comfort and adherence to the therapy.

Objective: To evaluate the effects of lipid-containing Rohto Dry Aid eye drops and sodium hyaluronate eye drops on the ocular surface and in vivo confocal microscopy (IVCM) findings in patients using systemic isotretinoin.

Methods: This retrospective study included 71 patients using systemic isotretinoin for acne vulgaris. Ocular surface and tear functions were evaluated with the tear break-up time (TBUT), corneal fluorescein staining (CFS), and the ocular surface disease index questionnaire (OSDI). Meibography was used for the staging of Meibomian gland dysfunction (MGD) while IVCM was used for the analysis of corneal micro-structural changes. The data of 36 patients using Rohto Dry Aid (the Rohto group) and 35 patients using sodium hyaluronate (the SH group) were recorded. Pre-treatment, first month and third month data were analyzed.

Results: Longer TBUT, lower OSDI score, and less CFS were observed in the first and third months after treatment in the Rohto group (p < 0.001). There was no significant change in TBUT and CFS in the first month (p > 0.05) in the SH group (p < 0.05) but lower TBUT and more CFS were observed in the third month. There was no significant change in the OSDI score in the SH group. There was a significant decrease in dendritic cells, activated keratocytes, and nerve tortuosity with IVCM in both groups. However, no significant difference was found between the two groups.

Conclusion: Rohto Dry Aid, with its support of the lipid layer, is an effective and safe treatment agent that can improve both ocular surface and IVCM findings in evaporative dry eye cases with MGD.