5-ALA/SFC Ameliorates Endotoxin-Induced Ocular Inflammation in Rats by Inhibiting the NF-κB Signaling Pathway and...

Area of Science:

• Ophthalmology
• Immunology
• Pharmacology

Background:

• Sodium ferrous citrate (SFC) is known to influence 5-aminolevulinic acid (5-ALA) metabolism and enhance its anti-inflammatory properties.
• Endotoxin-induced uveitis (EIU) is a common animal model for studying ocular inflammation.
• The specific effects of 5-ALA/SFC on EIU have not been fully investigated.

Purpose of the Study:

• To investigate the anti-inflammatory effects of 5-aminolevulinic acid combined with sodium ferrous citrate (5-ALA/SFC) in a rat model of endotoxin-induced uveitis (EIU).
• To elucidate the underlying molecular pathways involved in the anti-inflammatory action of 5-ALA/SFC in EIU.

Main Methods:

• Rats with EIU were treated with 5-ALA/SFC or 5-ALA alone via gastric gavage.
• Ocular inflammation was assessed by clinical scores, cell infiltration, aqueous humor protein levels, and histopathology.
• Immunohistochemistry was used to evaluate the expression of key inflammatory markers, including iNOS, COX-2, NF-κB, IκB-α, p-IKKα/β, HO-1, and Nrf2.

Main Results:

• 5-ALA/SFC significantly ameliorated ocular inflammation in EIU rats, comparable to a high dose of 5-ALA alone.
• Treatment reduced clinical scores, inflammatory cell infiltration, aqueous humor protein, and improved histopathological findings.
• 5-ALA/SFC suppressed iNOS, COX-2, NF-κB activation, IκB-α degradation, and p-IKKα/β expression.
• The treatment activated HO-1 and Nrf2 expression, indicating the involvement of the HO-1/Nrf2 pathway.

Conclusions:

• 5-ALA/SFC demonstrates significant anti-inflammatory effects in EIU rats.
• The therapeutic action of 5-ALA/SFC involves the inhibition of the NF-κB pathway and activation of the HO-1/Nrf2 pathway.
• 5-ALA/SFC presents a promising therapeutic agent for managing ocular inflammation.