Affiliation:
1. Federal University of Ceará
2. Federal Institute of Education, Science and Technology of Ceará
3. Federal University of Sergipe, #Corresponding author – Alexandre Havt
Abstract
Abstract
Acrolein is the main toxic metabolite of Ifosfamide (IFO) that causes urothelial damage by oxidative stress and inflammation. Here we investigate the molecular mechanism of action of gingerols, Zingiber officinale bioactive molecules, as an alternative treatment for ifosfamide-induced hemorrhagic cystitis. Female Swiss mice were randomly divided into 5 groups: control; IFO; IFO + Mesna; and IFO + [8]- or [10]-gingerol. Mesna (80 mg/kg, i.p.) was given 5 minutes before, 4 and 8 hours after IFO (400mg/kg, i.p.). Gingerols (25 mg/Kg, p.o.) were given 1 hour before and 4 and 8 hours after IFO. Animals were euthanized 12 hours after IFO injection. Bladders were submitted to macroscopic and histological evaluation. Oxidative stress and inflammation were assessed by malondialdehyde (MDA) or myeloperoxidase assays, respectively. mRNA gene expression was performed to evaluate Mesna and gingerols mechanisms of action. Mesna was able to protect bladder tissue by activating NF-κB and NrF2 pathways. However, we demonstrated that gingerols acted as an antioxidant and anti-inflammatory agent stimulating the production of IL-10, which intracellularly activated JAK/STAT/FOXO signaling pathway.
Publisher
Research Square Platform LLC
Cited by
1 articles.
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