Abstract:
CONTEXT:Lipopolysaccharide (LPS) exacerbates systemic inflammatory responses and causes excessive fluid leakage. 2,4,6-Trihydroxy-3-geranyl acetophenone (tHGA) has been revealed to protect against LPS-induced vascular inflammation and endothelial hyperpermeability in vitro. OBJECTIVE:This study assesses the in vivo protective effects of tHGA against LPS-induced systemic inflammation and vascular permeability in endotoxemic mice. MATERIALS AND METHODS:BALB/c mice were intraperitoneally pre-treated with tHGA for 1 h, followed by 6 h of LPS induction. Evans blue permeability assay and leukocyte transmigration assay were performed in mice (n = 6) pre-treated with 2, 20 and 100 mg/kg tHGA. The effects of tHGA (20, 40 and 80 mg/kg) on LPS-induced serum TNF-α secretion, lung dysfunction and lethality were assessed using ELISA (n = 6), histopathological analysis (n = 6) and survivability assay (n = 10), respectively. Saline and dexamethasone were used as the negative control and drug control, respectively. RESULTS:tHGA significantly inhibited vascular permeability at 2, 20 and 100 mg/kg with percentage of inhibition of 48%, 85% and 86%, respectively, in comparison to the LPS control group (IC50=3.964 mg/kg). Leukocyte infiltration was suppressed at 20 and 100 mg/kg doses with percentage of inhibition of 73% and 81%, respectively (IC50=17.56 mg/kg). However, all tHGA doses (20, 40 and 80 mg/kg) failed to prevent endotoxemic mice from lethality because tHGA could not suppress TNF-α overproduction and organ dysfunction. DISCUSSION AND CONCLUSIONS:tHGA may be developed as a potential therapeutic agent for diseases related to uncontrolled vascular leakage by combining with other anti-inflammatory agents.
journal_name
Pharm Bioljournal_title
Pharmaceutical biologyauthors
Chan YH,Musa NF,Chong YJ,Saat SA,Hafiz F,Shaari K,Israf DA,Tham CLdoi
10.1080/13880209.2021.1933083keywords:
["LPS","endothelial hyperpermeability","tHGA","vascular inflammation"]subject
Has Abstractpub_date
2021-12-01 00:00:00pages
732-740issue
1eissn
1388-0209issn
1744-5116journal_volume
59pub_type
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