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Systemic sclerosis is a fibrotic autoimmune disease in which aberrant remodeling of the extracellular matrix in organs disturbs their functionalities. The aim of this study was to investigate the expression of gelatinases on systemic sclerosis. Consequently, a mouse model of systemic sclerosis was employed and the gelatinolytic activity of gelatinases was evaluated on the fibrotic tissues of this model. Two groups of ten mice were considered in this work: a group of systemic sclerosis model and control group. For the generation of systemic sclerosis model, mice received bleomycin, while the control group was subjected to phosphate buffered saline (PBS) reception. Mice were tested for fibrosis by using trichrome staining, hydroxyproline measurement and α-SMA detection in tissue sections. Additionally, the gelatinolytic activity of matrix metalloproteinase 2 and matrix metalloproteinase 9 were measured using gelatin zymography in lungs and skin tissue homogenates. The obtained results indicated that subcutaneous injection of bleomycin-induced fibrosis in skin and lung tissues of mice. Pro and active forms of matrix methaloproteinase 9 were increased in fibrotic lung tissues (p<0.05 and p<0.01, respectively), while, the gelatinolytic activity of MMP2 was unaffected in these tissues. Additionally, in skin tissues of bleomycin-treated animals, both pro and active forms of MMP9 and MMP2 were increased (p<0.05). Pro and active forms of gelatinases increase differently in skin and lung tissues of bleomycin-induced scleroderma.

Systemic sclerosis is a female predominant, a fibrotic autoimmune disease in which disturbance in tissue homeostasis and cell turnover including cell apoptosis are central events in pathogenesis. Sex hormones are known as the important players in sexual dimorphism of autoimmune diseases and in tissue homeostasis. Progesterone influences autoimmune disease via its immunomodulatory effect or by its direct action on parenchymal cell function. On the other hand, this hormone impacts tissue homeostasis by acting on cell apoptosis in a different situation. The objective of this study was to examine the effect of progesterone on cellular apoptosis of skin and lung tissues in a mouse model of scleroderma. Four group of mice were involved in this study with 10 mice in each. The fibrotic model was induced by daily subcutaneous injection of bleomycin for 28 days. One week after initiation of fibrosis induction, mice received subcutaneous progesterone alone or with bleomycin for 21 days. Control group received only Phosphate buffered saline PBS. After 28 days, under lethal anesthesia skin and lung tissues were harvested for histological assessment and hydroxyproline measurement. Apoptosis in tissue sections was detected by TUNEL assay technique. Bleomycin administration induced fibrosis in skin and lung tissues. Severe apoptosis was seen in skin and lung tissues of the bleomycin-treated group (p<0.001 in the skin and p<0.05 in the lung). Progesterone injection either in the skin (p>0.05) or in the lung (p>0.05) did not alter apoptosis in bleomycin-treated animals. Our data confirm the role of apoptosis in the pathogenesis of fibrosis in this model; however, progesterone does not affect cellular apoptosis in skin and lung tissues of bleomycin-injured animals.

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Background: Pomegranate (Punica granatum) is a significant source of bioactive compounds. However, its toxicity is not intensively studied. Objectives: The current study investigated the safety and tolerability of pomegranate peel extract (PPE) in BALB/c mice. Materials and Methods: A total of 25 female BALB/c mice were randomly grouped. Each experimental group consisted of five animals. Repeated doses including 0.5, 1.9 and 7.5 mg/kg body weight of PPE were gavaged to BALB/c mice, for 22 days and the single intra-dermal injection (224 mg/kg) was done in one dose. The control group administrated with distilled water was also included. In addition, intra dermal injection for skin allergy testing was also performed. Blood was collected to evaluate glucose, cholesterol, alanine aminotransferase (ALT) and aspartate aminotransferase (AST) as indicators of liver toxicity. Macroscopic and histopathological evaluation of tongue, trachea, and larynx tissues were also performed on 22 days post administration. Results: Toxicological potential of PPE studies revealed no toxic effects, clinical signs, histopathological effect in epithelial cells layer of tongue, larynx and trachea, behavioral alterations and adverse effects or mortality in BALB/c mice. Repeated administrations did not alter or cause local irritation of the oral mucosa. Skin allergy test was negative in the last group. Conclusions: The current study showed that PPE had no toxicity and its use is suggested with potential applications against diseases.