Decoding the effect of Diceratella elliptica on the oxidative stress–Inflammation axis in hyperthyroid-induced hepatotoxicity

Abstract

BACKGROUND: Hyperthyroidism frequently impairs liver function through oxidative stress, inflammation, and apoptosis. Effective hepatoprotective therapies remain limited, targeting the effects of natural agents such as Diceratella Elliptica. The current study assessed the hepatoprotective efficacy of Diceratella Elliptica (DE) in an experimental model of L-thyroxin-induced hyperthyroidism. METHODS: This study performed on 40 male albino rats randomly allocated equally into five groups, control group (HT), L-thyroxin alone (orally, 600 mg/kg daily for 12 days) or in combination with propyl Thiourcil (PU) (intraperitoneally, 10 mg/kg daily for 15 days), and Diceratella Elliptica extract in 200 mg/kg and 400 mg/kg (orally, with a daily dose for 15 days). Hepatic function (ALT, AST, total protein), oxidative stress markers (SIRT1, Nrf2, MDA, NO, GSH, SOD and CAT), inflammatory markers (HMGB1, TLR4, NFκ-B, IL-6 and TNF-α), and apoptotic marker (Caspase-3) were measured, alongside histopathological evaluation. RESULTS: Hyperthyroid rats exhibited marked hepatic injury, with significant elevations in ALT (+85 %), AST (+72 %), MDA (+90 %), NO (+65 %), TNF-α (+70 %), IL-6 (+68 %), and Caspase-3 (+60 %) (P < 0.05), accompanied by substantial reductions in SIRT1 (-45 %), Nrf2 (-40 %), GSH (-50 %), SOD (-42 %), and CAT (-38 %) compared to control. Treatment with D. Elliptica (especially 400 mg/kg) significantly restored liver function, normalizing ALT and AST by nearly 50 %, enhancing antioxidant enzyme activities by 35-55 %, and down-regulating inflammatory and apoptotic markers (p < 0.05). Histological examination revealed restoration of hepatic cords, reduced inflammatory infiltration, and preserved hepatocyte morphology. CONCLUSION: Diceratella Elliptica exerts potent hepatoprotective activity against hyperthyroidism-induced hepatic injury. Its concurrent activation of SIRT1 and Nrf2, along with suppression of NF-κB-mediated inflammation and Caspase-3-dependent apoptosis, suggests modulation of the oxidative stress-inflammation-apoptosis axis. These findings support Diceratella Elliptica as a promising natural therapeutic candidate for thyroid-related liver dysfunction.