Mitigation of sepsis-associated acute kidney injury by thymoquinone via targeting pyroptosis and attenuation of inflammation in C57BL/6 mice

OBJECTIVES: Acute kidney injury (AKI) is a severe, life-threatening complication of sepsis that often leads to renal failure. Thymoquinone, the main bioactive component of Nigella sativa, exhibits potent antioxidant and anti-inflammatory effects, protecting heart, liver, and kidney tissues in experimental studies. This study aimed to investigate the protective effects of thymoquinone on lipopolysaccharide (LPS)-induced AKI in mice by assessing oxidative stress, inflammatory mediators, pyroptosis factors, and renal function markers via modulation of oxidative stress and pyroptosis pathways. MATERIALS AND METHODS: Thirty-two male C57BL/6 mice (20-25 g) were randomized into four groups: control, LPS, and two LPS groups treated with thymoquinone solubilized in Cremophor (1 or 10 mg/kg). AKI was induced by intraperitoneal injection of LPS (10 mg/kg). After 24 hr, blood samples were collected for blood urea nitrogen (BUN), cystatin C, and serum creatinine assays. Kidney homogenates were analyzed for malondialdehyde (MDA), superoxide dismutase (SOD), nitrite, interleukin-6 (IL-6), nucleotide-binding domain, leucine-rich-containing family, pyrin domain-containing-3 (NLRP3), and caspase-1 levels. RESULTS: Thymoquinone (10 mg/kg; PO) significantly decreased BUN (P<0.05), cystatin C (P<0.05), and serum creatinine (P<0.05) levels. It also reduced MDA concentration (P<0.05) and increased SOD activity (P<0.05), while nitrite levels remained unchanged. Furthermore, IL-6, NLRP3, and caspase-1 were significantly lower (for all factors, P<0.05) in thymoquinone-treated mice compared to the LPS group. CONCLUSION: Thymoquinone effectively attenuates LPS-induced AKI, likely by reducing oxidative stress, inhibiting pyroptosis and inflammation, and enhancing antioxidant defenses.