Dataset Information

Effect of Sofosbuvir Administration and Its Withdrawal on the Submandibular Salivary Gland of Adult Male Albino Rats: A Histological and Ultra-Structural Study.

ABSTRACT: BACKGROUND:Sofosbuvir (SOF) was approved in 2013 as a part of first-line treatment for hepatitis C virus (HCV); it has activity against all genotypes with extrahepatic adverse effects have recently arisen. AIM:Investigating sofosbuvir-induced alterations in the rat submandibular salivary gland (SMSG). METHODS:A group of 80 adult albino rats weighing about ± 150 gm were used in the experiment. The rats were divided into 3 groups: Group I (control group) received distilled water, Group II (experimental group) divided into 2 subgroups and received SOF 40 mg/kg/day dissolved in distilled water for 1 and 3 months and Group III (recovery group) allowed for 1 month of recovery after SOF withdrawal. All animals were sacrificed; the SMSG was dissected, and specimens were examined histologically and ultra-structurally. RESULTS:Compared to Group I, Group II subgroup (1) showed acinar and ductal vacuolisation, discontinuity of the epithelial lining associated with retained secretion and congested blood vessels. These changes were found to be exaggerated in the subgroup (2) accompanied by acinar and ductal shrinkage, interstitial oedema, haemorrhage, chronic inflammatory cells infiltration and loss of gland compactness. Amelioration of the histological changes was detected in Group III after SOF withdrawal. The ultrastructural examination confirmed these histological results. CONCLUSION:SOF had induced apparent alterations in the structure and ultrastructure of SMSG. The SOF-induced alterations were time-dependent, attributed mainly to mitochondrial toxicity and partially ameliorated by its withdrawal.

SUBMITTER: Abdeen AM

PROVIDER: S-EPMC7061369 | biostudies-literature | 2019 Dec

REPOSITORIES: biostudies-literature

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Effect of Sofosbuvir Administration and Its Withdrawal on the Submandibular Salivary Gland of Adult Male Albino Rats: A Histological and Ultra-Structural Study.

Abdeen Asmaa Mahmoud AM Essawy Tarik T Mohammed Saher Sayed SS

Open access Macedonian journal of medical sciences 20191210 23

<h4>Background</h4>Sofosbuvir (SOF) was approved in 2013 as a part of first-line treatment for hepatitis C virus (HCV); it has activity against all genotypes with extrahepatic adverse effects have recently arisen.<h4>Aim</h4>Investigating sofosbuvir-induced alterations in the rat submandibular salivary gland (SMSG).<h4>Methods</h4>A group of 80 adult albino rats weighing about ± 150 gm were used in the experiment. The rats were divided into 3 groups: Group I (control group) received distilled wa ...[more]

PMID: 32165960

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Project description:BackgroundOrgan replacement regenerative therapy based on human adult stem cells may be effective for salivary gland hypofunction. However, the generated tissues are immature because the signaling factors that induce the differentiation of human salivary gland stem cells into salivary glands are unknown.MethodsIsolated human submandibular gland stem/progenitor cells (hSMGepiS/PCs) were characterized and three-dimensionally (3D) cultured to generate organoids and further induced by fibroblast growth factor 10 (FGF10) in vitro. The induced spheres alone or in combination with embryonic day 12.5 (E12.5) mouse salivary gland mesenchyme were transplanted into the renal capsules of nude mice to assess their development in vivo. Immunofluorescence, quantitative reverse transcriptase-polymerase chain reaction, calcium release analysis, western blotting, hematoxylin-eosin staining, Alcian blue-periodic acid-Schiff staining, and Masson's trichrome staining were performed to assess the structure and function of generated tissues in vitro and in vivo.ResultsThe isolated hSMGepiS/PCs could be long-term cultured with a stable genome. The organoids treated with FGF10 [FGF10 (+) group] exhibited higher expression of salivary gland-specific markers; showed spatial arrangement of AQP5+, K19+, and SMA+ cells; and were more sensitive to the stimulation by neurotransmitters than untreated organoids [FGF10 (-) group]. After heterotopic transplantation, the induced cell spheres combined with mouse embryonic salivary gland mesenchyme showed characteristics of mature salivary glands, including a natural morphology and saliva secretion.ConclusionFGF10 promoted the development of the hSMGepiS/PC-derived salivary gland organoids by the expression of differentiation markers, structure formation, and response to neurotransmitters in vitro. Moreover, the hSMGepiS/PCs responded to the niche in mouse embryonic mesenchyme and further differentiated into salivary gland tissues with mature characteristics. Our study provides a foundation for the regenerative therapy of salivary gland diseases.

Project description:Cleft formation during submandibular salivary gland branching morphogenesis is the critical step initiating the growth and development of the complex adult organ. Previous experimental studies indicated requirements for several epithelial cellular processes, such as proliferation, migration, cell-cell adhesion, cell-extracellular matrix (matrix) adhesion, and cellular contraction in cleft formation; however, the relative contribution of each of these processes is not fully understood since it is not possible to experimentally manipulate each factor independently. We present here a comprehensive analysis of several cellular parameters regulating cleft progression during branching morphogenesis in the epithelial tissue of an early embryonic salivary gland at a local scale using an on lattice Monte-Carlo simulation model, the Glazier-Graner-Hogeweg model. We utilized measurements from time-lapse images of mouse submandibular gland organ explants to construct a temporally and spatially relevant cell-based 2D model. Our model simulates the effect of cellular proliferation, actomyosin contractility, cell-cell and cell-matrix adhesions on cleft progression, and it was used to test specific hypotheses regarding the function of these parameters in branching morphogenesis. We use innovative features capturing several aspects of cleft morphology and quantitatively analyze clefts formed during functional modification of the cellular parameters. Our simulations predict that a low epithelial mitosis rate and moderate level of actomyosin contractility in the cleft cells promote cleft progression. Raising or lowering levels of contractility and mitosis rate resulted in non-progressive clefts. We also show that lowered cell-cell adhesion in the cleft region and increased cleft cell-matrix adhesions are required for cleft progression. Using a classifier-based analysis, the relative importance of these four contributing cellular factors for effective cleft progression was determined as follows: cleft cell contractility, cleft region cell-cell adhesion strength, epithelial cell mitosis rate, and cell-matrix adhesion strength.

Dataset Information

Effect of Sofosbuvir Administration and Its Withdrawal on the Submandibular Salivary Gland of Adult Male Albino Rats: A Histological and Ultra-Structural Study.

Publications

Effect of Sofosbuvir Administration and Its Withdrawal on the Submandibular Salivary Gland of Adult Male Albino Rats: A Histological and Ultra-Structural Study.

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