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Journal of Cancer Research and... 2018Cisplatin (CIS) is an influential chemotherapeutic agent in the treatment of several types of malignant solid tumors, but its clinical use is related with ototoxicity....
AIMS
Cisplatin (CIS) is an influential chemotherapeutic agent in the treatment of several types of malignant solid tumors, but its clinical use is related with ototoxicity. Oleuropein (OLE) is a natural antioxidant and scavenging free radicals. Here, we first explore the efficacy of OLE in pancreas against to the toxicity of CIS and also analyses its mechanism.
MATERIALS AND METHODS
Fifty-six Sprague-Dawley rats were equally divided into eight groups, including, control group which received 7 mg/kg/day CIS intraperitoneally (i.p.) for 24 h, groups treated with doses of 50, 100, and 200 mg/kg OLE i.p. for 3 days, and groups which received same dose of CIS with three doses of OLE. After the treatments, animals were sacrificed. The oxidative DNA damage (8-hydroxy-2'-deoxyguanosine [8-OHdG]), total oxidative stress (TOS), total antioxidant status (TAS), and malondialdehyde (MDA) levels were evaluated in the pancreas. The histopathology of the pancreas was examined using three different staining methods: hematoxylin-eosin, periodic acid-Schiff, and alcian blue. Serum was provided to assess pancreatic function the lipase and amylase values.
RESULTS
The results showed that CIS significantly increased the level of TOS, MDA, and 8-OHdG in tissue as compared to the control group. Moreover, severe tissue damages were detected in the pancreas. Whereas, OLE at high dose significantly decreased the formations of 8-OHdG, the level of MDA, and increased levels of TAS in tissue samples. In the CIS group, the levels of amylase and lipase increased compared with the control group. However, there were statistically significant differences among the CIS group and the CIS + OLE groups in the values of both amylase and lipase. In addition, histopathological findings observed in CIS group in the pancreatic tissue alleviated in CIS + OLE groups.
CONCLUSION
We hope that the results of this study will provide an impetus for future investigations of novel treatment strategies for OLE in pancreas due to CIS.
Topics: Animals; Anti-Infective Agents; Antineoplastic Agents; Cisplatin; DNA Damage; Iridoid Glucosides; Iridoids; Male; Malondialdehyde; Oxidative Stress; Pancreas; Rats; Rats, Sprague-Dawley
PubMed: 29893338
DOI: 10.4103/jcrt.JCRT_1040_16 -
Signal Transduction and Targeted Therapy Apr 2024
Topics: Humans; SARS-CoV-2; Pandemics; COVID-19; Pancreas
PubMed: 38627360
DOI: 10.1038/s41392-024-01807-2 -
Nature Reviews. Endocrinology Apr 2021
Topics: COVID-19; Humans; Pancreas; Pancreas, Exocrine; SARS-CoV-2
PubMed: 33627835
DOI: 10.1038/s41574-021-00481-6 -
Gut and Liver Jul 2014Endoscopic drainage for pancreatic and peripancreatic fluid collections (PFCs) has been increasingly used as a minimally invasive alternative to surgical or percutaneous... (Review)
Review
Endoscopic drainage for pancreatic and peripancreatic fluid collections (PFCs) has been increasingly used as a minimally invasive alternative to surgical or percutaneous drainage. Recently, endoscopic ultrasound-guided transluminal drainage (EUS-TD) has become the standard of care and a safe procedure for nonsurgical PFC treatment. EUS-TD ensures a safe puncture, avoiding intervening blood vessels. Single or multiple plastic stents (combined with a nasocystic catheter) were used for the treatment of PFCs for EUS-TD. More recently, the use of covered self-expandable metallic stents (CSEMSs) has provided a safer and more efficient approach route for internal drainage. We focused our review on the best approach and stent to use in endoscopic drainage for PFCs. We reviewed studies of EUS-TD for PFCs based on the original Atlanta Classification, including case reports, case series, and previous review articles. Data on clinical outcomes and adverse events were collected retrospectively. A total of 93 patients underwent EUS-TD of pancreatic pseudocysts using CSEMSs. The treatment success and adverse event rates were 94.6% and 21.1%, respectively. The majority of complications were of mild severity and resolved with conservative therapy. A total of 56 patients underwent EUS-TD using CSEMSs for pancreatic abscesses or infected walled-off necroses. The treatment success and adverse event rates were 87.8% and 9.5%, respectively. EUS-TD can be performed safely and efficiently for PFC treatment. Larger diameter CSEMSs without additional fistula tract dilation for the passage of a standard scope are needed to access and drain for PFCs with solid debris.
Topics: Abdominal Abscess; Drainage; Endosonography; Humans; Necrosis; Pancreas; Pancreatic Diseases; Pancreatic Pseudocyst; Stents; Surgery, Computer-Assisted; Ultrasonography, Interventional
PubMed: 25071899
DOI: 10.5009/gnl.2014.8.4.341 -
Cell Reports. Medicine Aug 2021Enteroviral infections have been associated with autoimmunity and type 1 diabetes (T1D), but reliable methods to ascertain localization of single infected cells in the...
Enteroviral infections have been associated with autoimmunity and type 1 diabetes (T1D), but reliable methods to ascertain localization of single infected cells in the pancreas were missing. Using a single-molecule-based fluorescent hybridization (smFISH) method, we detected increased virus infection in pancreases from organ donors with T1D and with disease-associated autoantibodies (AAb). Although virus-positive β cells are found at higher frequency in T1D pancreases, compared to control donors, but are scarce, most virus-positive cells are scattered in the exocrine pancreas. Augmented CD45 lymphocytes in T1D pancreases show virus positivity or localization in close proximity to virus-positive cells. Many more infected cells were also found in spleens from T1D donors. The overall increased proportion of virus-positive cells in the pancreas of AAb and T1D organ donors suggests that enteroviruses are associated with immune cell infiltration, autoimmunity, and β cell destruction in both preclinical and diagnosed T1D.
Topics: Autoantibodies; Diabetes Mellitus, Type 1; Enterovirus; Humans; Lymphocytes; Pancreas; RNA, Viral; Spleen; Tissue Donors
PubMed: 34467248
DOI: 10.1016/j.xcrm.2021.100371 -
Journal of Virology Jun 2007Rotaviruses have been implicated as a possible viral trigger for exacerbations in islet autoimmunity, suggesting they might modulate type 1 diabetes development. In this...
Rotaviruses have been implicated as a possible viral trigger for exacerbations in islet autoimmunity, suggesting they might modulate type 1 diabetes development. In this study, the ability of rotavirus strain RRV to infect the pancreas and affect insulitis and diabetes was examined in nonobese diabetic (NOD) mice, an experimental model of type 1 diabetes. Mice were inoculated either orally or intraperitoneally as infants or young adults. In infant mice inoculated orally, rotavirus antigen was detected in pancreatic macrophages outside islets and infectious virus was found in blood cells, pancreas, spleen, and liver. Extraintestinal RRV spread and pancreatic presence of infectious virus also occurred in intraperitoneally inoculated infant and adult mice. The initiation of insulitis was unaltered by infection. The onset of diabetes was delayed in infant mice inoculated orally and infant and adult mice inoculated intraperitoneally. In contrast, adult mice inoculated orally showed no evidence of pancreatic RRV, the lowest rate of detectable RRV replication, and no diabetes modulation. Thus, the ability of RRV infection to modulate diabetes development in infant and young adult NOD mice was related to the overall extent of detectable virus replication and the presence of infectious virus extraintestinally, including in the pancreas. These studies show that RRV infection of infant and young adult NOD mice provides significant protection against diabetes. As these findings do not support the hypothesis that rotavirus triggers autoimmunity related to type 1 diabetes, further research is needed to resolve this issue.
Topics: Administration, Oral; Animals; Diabetes Mellitus, Type 1; Disease Models, Animal; Glucose; Immunoenzyme Techniques; Immunohistochemistry; Islets of Langerhans; Mice; Mice, Inbred NOD; Pancreas; Rotavirus; Rotavirus Infections; Time Factors; Tissue Distribution
PubMed: 17428851
DOI: 10.1128/JVI.00205-07 -
PloS One 2014Rotavirus is a ubiquitous double-stranded RNA virus responsible for most cases of infantile gastroenteritis. It infects pancreatic islets in vitro and is implicated as a...
Rotavirus is a ubiquitous double-stranded RNA virus responsible for most cases of infantile gastroenteritis. It infects pancreatic islets in vitro and is implicated as a trigger of autoimmune destruction of islet beta cells leading to type 1 diabetes, but pancreatic pathology secondary to rotavirus infection in vivo has not been documented. To address this issue, we inoculated 3 week-old C57Bl/6 mice at weaning with rhesus rotavirus, which is closely related to human rotaviruses and known to infect mouse islets in vitro. Virus was quantified in tissues by culture-isolation and enzyme-linked immunosorbent assay. A requirement for viral double stranded RNA was investigated in toll-like receptor 3 (TLR3)-deficient mice. Cell proliferation and apoptosis, and insulin expression, were analyzed by immunohistochemistry. Following rotavirus inoculation by gavage, two phases of mild, transient hyperglycemia were observed beginning after 2 and 8 days. In the first phase, widespread apoptosis of pancreatic cells was associated with a decrease in pancreas mass and insulin production, without detectable virus in the pancreas. These effects were mimicked by injection of the double-stranded RNA mimic, polyinosinic-polycytidylic acid, and were TLR3-dependent. By the second phase, the pancreas had regenerated but islets were smaller than normal and viral antigen was then detected in the pancreas for several days. These findings directly demonstrate pathogenic effects of rotavirus infection on the pancreas in vivo, mediated initially by the interaction of rotavirus double-stranded RNA with TLR3.
Topics: Animals; Apoptosis; Female; Humans; Hyperglycemia; Insulin; Islets of Langerhans; Male; Mice; Mice, Inbred C57BL; Organ Size; Regeneration; Rotavirus; Time Factors; Toll-Like Receptor 3; Weaning
PubMed: 25181416
DOI: 10.1371/journal.pone.0106560 -
Interdisciplinary Sciences,... Dec 2022The SARS-CoV-2 infection affects the lungs, heart, kidney, intestine, olfactory epithelia, liver, and pancreas and brings forward multi-organ dysfunctions (MODs)....
The SARS-CoV-2 infection affects the lungs, heart, kidney, intestine, olfactory epithelia, liver, and pancreas and brings forward multi-organ dysfunctions (MODs). However, mechanistic details of SARS-CoV-2-induced MODs are unclear. Here, we have investigated the role of pancreatic secretory proteins to mechanistically link COVID-19 with MODs using single-cell transcriptome analysis. Secretory proteins were identified using the Human Protein Atlas. Gene ontology, pathway, and disease enrichment analyses were used to highlight the role of upregulated pancreatic secretory proteins (secretome). We show that SARS-CoV-2 infection shifts the expression profile of pancreatic endocrine cells to acinar and ductal cell-specific profiles, resulting in increased expression of acinar and ductal cell-specific genes. Among all the secretory proteins, the upregulated expression of IL1B, AGT, ALB, SPP1, CRP, SERPINA1, C3, TFRC, TNFSF10, and MIF was mainly associated with disease of diverse organs. Extensive literature and experimental evidence are used to validate the association of the upregulated pancreatic secretome with the coagulation cascade, complement activation, renin-angiotensinogen system dysregulation, endothelial cell injury and thrombosis, immune system dysregulation, and fibrosis. Our finding suggests the influence of an upregulated secretome on multi-organ systems such as nervous, cardiovascular, immune, digestive, and urogenital systems. Our study provides evidence that an upregulated pancreatic secretome is a possible cause of SARS-CoV-2-induced MODs. This finding may have a significant impact on the clinical setting regarding the prevention of SARS-CoV-2-induced MODs.
Topics: Humans; COVID-19; SARS-CoV-2; Angiotensinogen; Multiple Organ Failure; Renin; Secretome; Pancreas; Gene Expression Profiling
PubMed: 35394619
DOI: 10.1007/s12539-022-00513-3 -
Frontiers in Cellular and Infection... 2018Coxsackievirus B3 (CVB3) is the primary cause of viral myocarditis. An early and abundant neutrophil accumulation in the myocardium is a hallmark of early CVB3...
Coxsackievirus B3 (CVB3) is the primary cause of viral myocarditis. An early and abundant neutrophil accumulation in the myocardium is a hallmark of early CVB3 infection. Yet the relative contribution of neutrophils to host susceptibility to CVB3 myocarditis remains largely unknown. Herein, peripheral neutrophil depletion was implemented in a BALB/c mouse model of acute CVB3 myocarditis using the specific 1A-8 (anti-Ly6G) or a RB6-8C5 (anti-Gr-1) mAb covering a wide range. Anti-Ly6G treatment led to systemic neutropenia throughout the disease, but did not alter virus replication, disease susceptibility and histopathological changes in the heart and pancreas of mice. In contrast, depletion of both neutrophils and monocytes/macrophages by anti-Gr-1 mAb prior to and after infection significantly promoted susceptibility of mice to CVB3 infection which was associated with exacerbated cardiac and pancreatic viral load. However, depletion of Gr1+ cells significantly suppressed acute myocarditis and pancreatic acini destruction at day 7 post infection via reducing Ly6C monocyte population in the circulation. Additionally, cardiac interstitial fibrosis was not affected by neutrophil depletion, whereas Gr-1+ cells other than neutrophils increased cardiac fibrosis at day 21 p.i. by increasing cardiac expression of profibrotic cytokine TNF-α and TGF-β. Thus, Neutrophil function is most likely not essential for CVB3 control and peripheral neutrophils play dispensable role in the pathogenesis of acute myocarditis and pancreatitis during CVB3 infection. Whereas Gr-1+ cells other than neutrophils play a major role in limiting viral replication while promoting myocardial and pancreatic inflammatory injury and fibrosis.
Topics: Animals; Antigens, Ly; Coxsackievirus Infections; Cytokines; Disease Models, Animal; Fibrosis; Heart; Inflammation; Leukocytes; Male; Mice; Mice, Inbred BALB C; Myocarditis; Neutropenia; Neutrophils; Pancreas; Receptors, Chemokine; Transforming Growth Factor beta; Tumor Necrosis Factor-alpha; Viral Load; Virus Replication
PubMed: 29868513
DOI: 10.3389/fcimb.2018.00157 -
Genes Mar 2021Newcastle disease virus (NDV) causes a highly contagious and devastating disease in poultry. ND causes heavy economic losses to the global poultry industry by decreasing...
Newcastle disease virus (NDV) causes a highly contagious and devastating disease in poultry. ND causes heavy economic losses to the global poultry industry by decreasing the growth rate, decrease in egg production high morbidity and mortality. Although significant advances have been made in the vaccine development, outbreaks are reported in vaccinated birds. In this study, we report the damage caused by NDV infection in the pancreatic tissues of vaccinated and specific-pathogen-free chickens. The histopathological examination of the pancreas showed severe damage in the form of partial depletion of zymogen granules, acinar cell vacuolization, necrosis, apoptosis, congestion in the large and small vessels, sloughing of epithelial cells of the pancreatic duct, and mild perivascular edema. Increased plasma levels of corticosterone and somatostatin were observed in NDV-infected chicken at three- and five- days post infection (DPI). A slight decrease in the plasma concentrations of insulin was noticed at 5 DPI. Significant changes were not observed in the plasma levels of glucagon. Furthermore, NDV infection decreased the activity and mRNA expression of amylase, lipase, and trypsin from the pancreas. Taken together, our findings highlight that NDV induces extensive tissue damage in the pancreas, decreases the activity and expression of pancreatic enzymes, and increases plasma corticosterone and somatostatin. These findings provide new insights that a defective pancreas may be one of the reasons for decreased growth performance after NDV infection in chickens.
Topics: Animals; Chickens; Islets of Langerhans; Newcastle Disease; Newcastle disease virus; Pancreas, Exocrine; Pancreatitis; Poultry Diseases
PubMed: 33805275
DOI: 10.3390/genes12040495