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    Biochemical and histopathologic assessment of effects of acitretin on epiphyseal growth plate in rats
    (TERMEDIA PUBLISHING HOUSE LTD, 2020) Onder, Sevda; Bilgili, Serap Gunes; Bulut, Gulay; Celik, Huseyin Tugrul; Oguztuzun, Serpil; Onder, Haci; Calka, Omer
    Introduction: Acitretin is a commonly used retinoid in dermatology. Although there are generally known side effects, the effects on the epiphyseal plaque and bone metabolism are not clear in the literature. Aim: To histopathologically investigate the effects on the epiphyseal plate and assess variations in bone metabolism caused by acitretin. Material and methods: Three groups were formed with 10 rats in each group. The 1st group (n = 10, 5 male, 5 female) were administered 10 mg/kg/day oral acitretin solution and the 2nd group (n = 10, 5 male, 5 female) were administered 3 mg/kg/day oral acitretin solution. The control group were given normal standard feed and water. Rats were sacrificed at the end of 4 weeks. The proximal tibias were excised and histopathologically and immunohistochemically assessed. Biochemical assessment was also carried out. Results: Staining with haematoxylin-eosin found reductions in the epiphyseal plate in the 1st and 2nd group compared to the control group, though this situation was not statistically significant. Immunohistochemical studies did not encounter Type II collagen in the epiphyseal bone, proliferative zone and hypertrophic zone in the control group, low dose acitretin solution group and high dose acitretin solution group. Type II collagen was not observed in osteoids and osteoblasts. Type I collagen was not observed in the hypertrophic zone and proliferative zone of any group. Conclusions: Our data show that though acitretin caused degeneration of the epiphyseal plate, it did not cause clear thinning and we identified no significant variations in bone metabolism markers.
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    Effects of Different Doses of Systemic Isotretinoin on Eyes: A Histopathological and Immunohistochemical Study in Rats
    (Lippincott Williams & Wilkins, 2020) Karadag, Remzi; Karadag, Ayse Serap; Ozlu, Emin; Oguztuzun, Serpil; Simsek, Gulcin Guler; Esmer, Oktay; Bilgili, Serap Gunes
    Purpose: To evaluate ocular side effects associated with systemic isotretinoin histopathologically. Methods: In this multicenter study, a total of 15 male and 15 female rats were randomly divided into 3 equal groups according to the oral dose of isotretinoin they were administered: 0 mg/kg/d (group A), 7.5 mg/kg/d (group B), and 15 mg/kg/d (group C). Biopsy specimens were taken from the globe conjunctiva, cornea, and eyelid conjunctiva. Expression levels of human beta-defensin-1, human beta-defensin-2, toll-like receptor (TLR)-2, and TLR-4 were evaluated by immunohistochemical methods. Results: The number of goblet cells in eyelid conjunctiva was significantly lower in group B than that in group A and group C (P = 0.002). The sizes of meibomian gland acini were significantly smaller in group B and group C than those in group A (P < 0.001). Fibrosis of eyelid conjunctiva was significantly higher in group C and group B than that in group A (P = 0.002). The levels of staining of TLR-4 in the cornea with group B were significantly lower compared with group C (P = 0.035). Conclusions: Our study suggests that isotretinoin in the early period affects eyelid conjunctiva and meibomian glands without affecting the globe conjunctiva and cornea. Occurrence of the initial symptoms of isotretinoin on the eyelids, especially on the meibomian glands, suggests that the symptoms of patients occur because of evaporative dry eye.
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    Expressions of glutathione S-transferase alpha, mu, pi, and theta in the skin samples of patients with acne rosacea
    (WILEY, 2020) Takci, Zennure; Bilgili, Serap Gunes; Kilic, Murat; Oguztuzun, Serpil; Bozer, Busra; Simsek, Gulcin Guler; Akbayrak, Atiye
    Background Data point to the importance of oxidative stress in rosacea. Glutathione S-transferases (GSTs) have substantial roles in a wide variety of oxidative stress-related conditions. Aim To evaluate the immunohistochemical staining characteristics of GST alpha (GSTA), mu (GSTM), pi (GSTP), and theta (GSTT) in patients with rosacea. Patients/Methods The study included 23 women and 7 men with rosacea (mean +/- SD age 49 +/- 11 year) and 15 healthy control subjects (10 women, 5 men; mean +/- SD age 47.86 +/- 10.88 year). For each patient, the average disease duration, disease subtype, ocular involvement, and severity score were recorded. A 3-mm punch biopsy was taken from the facial skin of each patient and control. Expression of GST isoenzymes was analyzed immunohistochemically. Results Expressions of GSTM1, GSTP1, and GSTT1 were significantly elevated in patients with rosacea compared to those in the control group (P = .0001,P = .0002,P < .0001, respectively). In the rosacea group, GSTT1 expression was significantly stronger than GSTP1 and GSTA1 expressions (P = .019,P < .0001, respectively). There were no significant associations between expressions of GST isoenzymes and gender, age, average duration of illness, disease subtype, ocular involvement, or severity score in the patient group (allP > .05). Conclusions In rosacea, the significant increase of GSTT1, GSTP1, and GSTM1 expressions might result from activation of GST as an outcome of extreme free radical generation from triggered neutrophils or ultraviolet vulnerability. These findings support the relevance of oxidant stress in the pathogenesis of rosacea.