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1.
Pharmacol Res Perspect ; 11(4): e01108, 2023 08.
Article in English | MEDLINE | ID: mdl-37424158

ABSTRACT

Cisplatin is clinically proven to combat different cancers, including sarcomas, soft tissue cancers, bones, muscles, and blood. However, renal and cardiovascular toxicities are important limitations in cisplatin therapeutical use. Immunoinflammation could be key factor in cisplatin-induced toxicity. The aim of the present study was to evaluate the activation of the inflammatory TLR4/NLRP3 pathway as a common mechanism for cardiovascular and renal cisplatin's cycles treatment toxicity. Adult male Wistar rats were treated with saline, cisplatin 2 mg/kg or cisplatin 3 mg/kg (intraperitoneally once a week, for five experimental weeks). After treatments, plasma, cardiac, vascular, and renal tissues were collected. Plasma malondialdehyde (MDA) and inflammatory cytokines were determined. TLR4, MyD88, NF-κß p65, NLRP3, and procaspase-1 tissue expressions were also analyzed. Cisplatin treatment induced a dose-dependent increase in plasma MDA and IL-18. In cardiovascular system, an increase in NLRP3 and in cleaved caspase-1 were observed in cardiac tissue and a moderate increase in TLR4, MyD88 appeared in mesenteric artery. In kidney, a significant dose-dependent increase in TLR4, MyD88 and NLRP3 and cleaved caspase 1 expressions were observed after cisplatin treatments. In conclusion, cisplatin cycles provoke a low grade pro-inflammatory systemic state. Kidney was more sensitive than cardiovascular tissues to this pro-inflammatory state. TLR4 and NLRP3 are key pathways involved in renal tissue damage, NLRP3 is the main pathway involved in cardiac toxicity and TLR4 pathway in resistance vessel toxicity.


Subject(s)
Cardiovascular System , NLR Family, Pyrin Domain-Containing 3 Protein , Rats , Animals , Male , NLR Family, Pyrin Domain-Containing 3 Protein/metabolism , Cisplatin , Signal Transduction , Toll-Like Receptor 4/metabolism , Myeloid Differentiation Factor 88/metabolism , Rats, Wistar , Kidney/metabolism , Cardiovascular System/metabolism
2.
Article in English | MEDLINE | ID: mdl-35897458

ABSTRACT

The prevalence of Helicobacter pylori (Hp) in bariatric patients is common and related to gastric pathology. With preoperative upper gastrointestinal endoscopy (UGE), these pathologies and the presence of Hp are diagnosed. The histopathological study of the UGE biopsies is classified based on the Sydney System, a scoring system that stages chronic gastritis (CG) and precancerous gastric lesions. The objective is to assess the histological findings of gastric biopsies during routine UGE and to determine the involvement of Hp in gastric disorders in patients undergoing bariatric surgery. A multicenter retrospective review of prospectively collected databases was performed. The presence of CG, gastric atrophy (GA), and gastric intestinal metaplasia (GIM) in the study of the biopsies was assessed and correlated with Hp infection. The incidence of Hp among our bariatric population was 36.1%, and it increases with age. The percentage of patients with severe Hp infection is higher in patients with GA or GIM. The Hp eradication rate is also reduced when GA and GIM are present. A histological examination of all the biopsies did not show features of malignancy in any of the cases. Hp is not the only factor involved in the development of gastric pathology in bariatric patients.


Subject(s)
Bariatric Surgery , Helicobacter Infections , Helicobacter pylori , Precancerous Conditions , Helicobacter Infections/epidemiology , Humans , Metaplasia , Precancerous Conditions/pathology
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