Cutaneous and Ocular Toxicology最新文献

Purpose: Dermal exposure to freshwaters contaminated with pesticides and microbial toxins may result in toxicity. This study assessed the in vitro dermal irritancy of selected pesticides and microbial toxins using two- (2D) and three-dimensional (3D) human skin models.

Materials and methods: The 2D model was normal human keratinocytes. The 3D model was EpiDerm, derived from normal human keratinocytes that forms a multi-layered differentiated human epidermal model. Pesticides included dimethipin, α-1,2,3,4,5,6-hexachlorocylohexane, oxyfluorfen, permethrin, profenofos, and tribufos. Toxins included cylindrospermopsin and microcystin-LA, -LR, and -RR. Exposure to contaminants was either 1 or 24 h. Viability was assessed by the MTT assay. Results were determined relative to negative control.

Results: Significant effects in viability were observed in both models and time points. The greatest significant decrease in viability in the 2D model was tribufos at 1 h (23%) and cylindrospermopsin (37%) at 24 h. In the 3D model, the greatest significant decrease was microcystin-LA (16%) at 1 h and microcystin-RR (32%) at 24 h.

Conclusion: Several microbial toxins and pesticides were cytotoxic in both models and time points. However, no contaminant tested in the 3D model for 1 h was > 50% cytotoxic, which would categorize a chemical as a dermal irritant (Organisation for Economic Cooperation and Development Test Guideline 439 for skin irritation). The 24 h exposure time point had a greater number of cytotoxic contaminants in both models, particularly the 2D model. Screening potential irritants in the 2D model for 24 h may prioritize chemicals for further assessment in the 3D model.

Introduction: Despite evidence supporting the therapeutic potential of Calendula officinalis, well-designed and controlled studies are still needed to confirm its beneficial effects on various health conditions, including skin care. This study therefore evaluates the effectiveness of topically administered 5% aqueous Calendula officinalis extract on healing full-thickness skin wounds in male BALB/c mice.

Methods: Seventy-two mice were divided into three groups: CAL (treated with calendula extract), PSS (treated with physiological saline), and NC (negative control/no treatment). Wound healing was assessed over 14 days using planimetric measurements, counting fibroblasts and macrophages, biochemical analyses of growth factors, inflammation markers, hydroxyproline levels, and genomic analyses.

Results: The data obtained show that the application of CAL extract significantly reduces wound areas by day 7 compared to the NC and PSS groups. CAL extract also leads to an increase in fibroblasts, fibroblast growth factor, and hydroxyproline levels, while it reduces macrophages and inflammatory biomarkers levels in the healing wound. Genomic analyses indicate that topical application of CAL extract significantly reduces the expression of inflammatory biomarkers, including matrix metalloproteinases 2 and 9.

Conclusions: These findings show that 5% aqueous CAL extract enhances wound healing promising new insights for the effective topical treatment of skin wounds.

Purpose: The main aim of this review is to provide an overview of the key ocular side effects associated with topical tacrolimus compounded ophthalmic preparations Materials and methods: Review of literature using Pubmed database.

Results: The use of topical tacrolimus may be associated with side effects ranging from mild ocular discomfort to more server complications like loss of integrity of corneal surface, corneal ulcer and infectious keratitis. However, the use of topical tacrolimus is not associated with increased incidence of secondary glaucoma or cataract.

Conclusion: It is imperative to understand the potential side effects associated with topical tacrolimus ophthalmic preparations to optimize the treatment outcomes and guarantee patient safety. Routine ophthalmic examinations should be conducted to detect these side effects early and address them appropriately.

Wound healing is an intricate, complicated process that needs special attention because of its related complications that may occur if not treated properly or because of therapeutic insufficiency. Common bugloss (Anchusa officinalis L.) is a deep-rooted, hairy perennial herb used in folk medicine for numerous human issues, including wound recovery. To delineate its safety and healing potentials, we investigated the acute toxicity and wound-healing effects of Anchusa officinalis L. (APEAO) aerial part extracts on excisional neck injury in rats. A uniform dorsal neck cut was formed in twenty-four albino rats, which were arbitrarily divided into 4 groups and treated daily with a topical 0.2 ml dose of the following: group A, rats received 10% tween 20; group B, rats received intrasite gel; groups C and D, rats had 250 and 500 mg/kg of APEAO, respectively. The APEAO treatment did not cause toxic damage in rats administered with up to 5 g/kg APEAO. In the wound experiment, APEAO-treated skin exhibited significantly higher deposition of tissue collagen and fibroblast cells. In contrast, inflammatory cells were significantly lower in the recovered tissues of than positve control rats. Topical application of APEAO caused positive modulation of Transforming Growth Factor Beta 1 (angiogenesis) in recovered skin, indicating elevated tissue growth and faster wound-healing action. Moreover, APEAO treatment caused a significant elevation in tissue antioxidants (Superoxide dismutase, glutathione peroxidase, and catalyze) and hydroxyproline (collagen) content, lowering Malondialdehyde levels compared to vehicle rats. Serum inflammatory chemicals (Transforming growth factor α, Interlukin-6, and Interlukin-10) were significantly modulated following APEAO application. The outcomes revealed significant tissue regeneration potentials of APEAO exhibited by its modulatory actions on several cellular processes, which could serve as scientific evidence for future investigation regarding the production of potent pharmaceuticals for faster wound contraction.

Purpose: To examine effects of topical antiglaucoma drops on ocular surface (OS)and meibomian glands(MG) in relation to drug type, number of drugs and drug intensity.

Methods: This was a cross-sectional case study of 93 patients with glaucoma treated with topical anti-glaucoma drugs for more than 1 year. According to drug type we formed two groups; Group 1: Prostaglandin containing drops(monotherapy and combination therapy), Group 2:Non -PGA therapy.According to drug number, we formed three groups; Group 1:One active drug compound, Group 2: Two active drug compounds, Group 3:Three or more active drug compounds.We formed 2 groups accrding to drug intensity index (DII); Group 1: DII was < 50, Group 2: DII ≥ 50.Conjonctival hyperemia, ocular surface staining, tear break-up time (TBUT), and eyelid signs representing meibomian gland disease (eyelid vascularity, irregularity, nature of meibum and the Marx line score) have been compared between groups.

Results: Prostaglandin containing drops group showed significantly worse results in comparison of TBUT, conjonctival hyperemia, ocular surface staining, lid margin vascularity, meibum quality, and Marx line score.Çonjonctival hyperemia, and lid margin vascularity were observed to be significantly higher in those using eye drops containing two or more active compounds.When the DII is increased only lid margin irregularity, and meibum quality are getting worse, significantly.

Conclusion: Our results showed that the main factor contrubuting to OSD and MGD were prostaglandin analog therapy as a drug type. Management of ocular surface disease in glaucomatous patients is important when trying to reduce further ocular morbidity.

Purpose: With the increasing use of diode lasers emitting in the visible light spectrum, concerns about their potential to dazzle and cause eye damage have grown. This study aims to determine the maximum safe exposure levels and evaluate the retinal damage and dazzling effects caused by red, green, blue, and synthetic white lasers.

Materials and methods: A chinchilla grey rabbit model was used for experimentation. Lasers with wavelengths of 635 nm (red), 520 nm (green), and 456 nm (blue), along with their combined output as synthetic white light, were directed at the rabbits' eyes for 0.2 s. Retinal damage was assessed using a fundus camera at 1 h and 24 h post-irradiation. Histological analysis was conducted to evaluate tissue changes. The dazzling effect was measured by recording the b-wave recovery time in the electroretinogram 0.1 s after laser exposure.

Results: The maximum safe power density levels for red, green, blue, and synthetic white lasers were found to be 140, 60, 35, and 55 mJ/cm², respectively. Exposures exceeding these thresholds resulted in visible retinal damage, including white-coagulated spots, hemorrhages, and corresponding histopathological changes. At an exposure level of 12.0 mJ/cm², the b-wave recovery times for green, blue, and synthetic white light were 9.0, 8.0, and 7.8 s, respectively, while no dazzling effect was observed with the red laser.

Conclusions: The synthetic white light laser exhibited slightly inferior safety compared to the green laser but was significantly safer than the blue laser, with fewer dazzling effects. These findings provide valuable insights for the safe use of visible light lasers.

Purpose: This study aimed to biochemically and histopathologically evaluate the protective and therapeutic effects of elamipretide and methylprednisolone on methanol poisoning-induced brain, optic nerve, and retinal toxicity.

Method: In this study, 40 male Wistar Albino rats were divided into six groups: healthy control (HC), methotrexate (MTX, 0.3 mg/kg/d for 7 d), methotrexate + methanol (MTX-M, 0.3 mg/kg/d for 7 d + methanol 3 g/kg on Day 8), methotrexate + methanol + methylprednisolone (MTX-M-MPZ, 0.3 mg/kg/d for 7 d + methanol 3 g/kg on Day 8 + MPZ 1 mg/kg/d for 3 d), methotrexate + methanol + elamipretide (MTX-M-E, 0.3 mg/kg/d for 7 d + methanol 3 g/kg on Day 8 + elamipretide 5 mg/kg/d for 3 d), and methotrexate + methanol + methylprednisolone + elamipretide (MTX-M-MPZ-E, 0.3 mg/kg/d for 7 d + methanol 3 g/kg on Day 8 + MPZ 1 mg/kg/d + Elamipretide 5 mg/kg/d for 3 d). The rats were euthanized 8 h after the last drug administration. Histopathological and biochemical evaluations were performed on serum, caudatoputamen, and ocular tissues. Retinal degeneration was assessed using a scoring system where higher scores indicate less degeneration, with a score of 5 representing normal structure and 1 reflecting severe degeneration.

Results: In the MTX-M-MPZ-E group, the retinal degeneration score was higher than in MTX-M group (p = 0.002). The apoptosis index in the retina was highest in MTX-M group, while it was lower in MTX-M-MPZ-E group compared to MTX-M group (p = 0.018). In addition, the apoptosis index in the caudatoputamen was lower in MTX-M-MPZ-E group compared to MTX-M group (p = 0.009).

Conclusion: Combined elamipretide and methylprednisolone treatment improved optic nerve and retinal degeneration, reduced neuronal degeneration in the caudatoputamen, decreased oxidative stress and lipid peroxidation, and reduced apoptosis in the retina and caudatoputamen.

Purpose: To assess changes in the thickness of macular sublayers in individuals taking hydroxychloroquine (HCQ) without any evident toxicity and to review the relevant literature.

Methods: This prospective case-control study examined 47 adults on HCQ without evident toxicity on spectral-domain optical coherence tomography (SD-OCT) and visual field tests, as well as 25 healthy controls. Macular thickness in different sublayers was measured using SD-OCT. The thickness of combination layers and the variability of sublayers were also recorded. Data were compared between the case and control groups, and the correlation between cumulative HCQ use and outcome measures was analysed.

Results: The average age of participants in the case and control groups was 45.6 ± 9.3 and 46.8 ± 11.7 years, respectively (p = 0.831). The percentage of female participants was 91.5% in the case group and 84.0% in the control group (p = 0.927). In the case group, the average duration of HCQ use was 5.1 ± 5.2 years, with a mean cumulative dose of 301 ± 365 g. No significant differences were found in the visual field mean deviation or pattern standard deviation between patients with HCQ use of <5-years vs. ≥5-years. Additionally, there were no statistically significant differences in various retinal thickness measurements between the case and control groups. However, a significant association was observed between the cumulative dose of HCQ and the thickness of the outer retinal layer (ORL) in both the outer (r = 0.344; p = 0.032) and inner Early Treatment Diabetic Retinopathy Study (ETDRS) macular rings (r = 0.303; p = 0.061).

Conclusions: No significant difference in macular sublayer thickness was found between patients taking HCQ without evident toxicity and the control group. A weak direct association was observed between the cumulative dose of HCQ and the ORL thickness. These findings suggest that analysing macular sublayer thickness may not be useful in detecting the earliest signs of presumed HCQ toxicity in individuals without classical sign of toxicity on qualitative SD-OCT or visual field test.

Introduction/objective: Anti-VEGF (Vascular endothelial growth factor) agents have revolutionized ophthalmotherapy and are vital for various retinal disease treatment in ophthalmic practice. Ophthalmology has witnessed an explosion in the number of intravitreal injections delivered to patients over the past years. The rising popularity of anti-VEGF drugs came along with concerns about its safety in clinical use. The aim of this focused review is to critically analyze currently available findings on systemic safety.

Materials and methods: A literature search was conducted using PubMed, Web of Science, and Google Scholar databases for studies published from January 2012 to February 2025. The reference lists of meta-analyses and selected studies were also reviewed. Eighty four articles of high or medium clinical relevance were selected for review. The exclusion criteria included non-English language publications, articles directly unrelated to the review topic, commentaries, conference abstracts.

Results: Systemic safety concern in intraocular pharmacotherapy by antiangiogenic agents has a strong body of clinical evidence, resulting in plenty of peer reviewed clinical articles. It is certainly becoming recognized that anti-VEGF agents, despite given intraocularly, have the potential to cause systemic adverse events, such as cardiovascular, renal, neurological.

Conclusions: Accumulating evidence obviate the need to raise medical professionals' awareness about systemic risk profile in patients with eye diseases treated by anti-VEGF, paying a special attention on patients with diabetes and older patients with multimorbidity. Early identification and prompt management of patients with undesirable systemic side effects secondary to intraocular pharmacotherapy by angiogenics can lessen disease severity, and help achieve earlier resolution.

Objectives: This study was to investigate the effects of atropine sulphate eye drops (ASED)on the development of partial systems in young rats and their toxic reactions following repeated eye-drop administration over a period of 40 days.

Methods: SD rats of 20 days old were randomly assigned to control group, 0.01, 0.02, and 0.04% ASED groups, with 60 females and 25 males per group. ASED was given by eye drops from PND₂₁ onwards and normal saline was given in the control group at 10 μL/eye once a day for 40 days, in both right and left eyes. Rats of ASED groups were instilled with eye drops at the 10 μL/day per eye, from postnatal day 21 (PND₂₁) to PND₆₀ for 40 consecutive days. The clinical observation, body weight, food intake, physical development, physiological development, reproductive development, ophthalmic examination, intraocular pressure, and axial length of the rats were examined during the study period.

Results: ASED at concentrations of 0.01, 0.02, 0.04%, dose levels of 0.002, 0.004, 0.008 mg/day per rat, had no toxicological effects on the clinical observation, body weight, food intake, physical development, physiological development, reproductive development, ophthalmic examination, intraocular pressure, and axial length in rats.

Conclusion: The no-observed-adverse-effect-level (NOAEL) of ASED in young SD rats equivalent to human over 2 years old was 0.008 mg/day at a concentration of 0.4 mg/mL.