Theranekron prevents endotoxin-induced acute kidney injury by modulating inflammatory and mitochondrial apoptotic pathways.

BACKGROUND

Lipopolysaccharide (LPS)-induced acute kidney injury (AKI) is characterized by oxidative stress, inflammation, and apoptotic injury. Theranekron (THERA) has been suggested to exert immunomodulatory effects; however, its impact on renal oxidative status and related molecular pathways remains unclear.

METHODS

Thirty-two male Wistar albino rats were allocated into four groups: Control, LPS, LPS + THERA, and THERA. Renal oxidative stress was assessed by measuring total antioxidant status (TAS), total oxidant status (TOS), and oxidative stress index (OSI). Serum creatinine and urea levels, histopathological alterations, and immunohistochemical expression of endothelial nitric oxide synthase (eNOS), interferon-gamma (IFN-γ), and interleukin-8 (IL-8) were evaluated. Sirtuin-1 (SIRT1), nuclear factor erythroid 2-related factor 2 (NRF2), heme oxygenase-1 (HO-1), B-cell lymphoma-2 (BCL2), BCL2-associated X protein (BAX), aquaporin-2 (AQP2), tumor necrosis factor-alpha (TNF-α), and interleukin-10 (IL-10) gene expression were measured.

RESULTS

LPS significantly increased urea and creatinine levels and induced marked renal histopathological injury. Renal TAS was significantly decreased, and OSI was significantly increased. THERA treatment significantly increased TAS and reduced OSI compared with the LPS group. LPS significantly reduced SIRT1, NRF2, and HO-1 mRNA expression, and prophylactic THERA treatment significantly increased only HO-1 expression. LPS induced a pro-apoptotic shift and reduced AQP2 expression, all of which were significantly prevented by THERA. In parallel, THERA significantly reduced TNF-α expression and IL-10 levels, decreased IFN-γ and IL-8 immunoreactivity, and reduced eNOS immunoreactivity.

CONCLUSION

Prophylactic THERA administration partially protected against early renal injury by improving renal antioxidant capacity, upregulating HO-1, and suppressing inflammatory and apoptotic responses, with preservation of AQP2 expression.