Green synthesized selenium nanoparticles using Trigonellafoenum–graecum exhibit antioxidant and anti-inflammatory effects against acetaminophen-induced nephrotoxicity in mice

Abstract

Acetaminophen (APAP) overdose induces nephropathy through multiple mechanisms, including oxidative stress, inflammation, and lipid peroxidation. In this study, we evaluated the renal protective effects of Trigonella foenum–graecum extract (TFGE), both alone and in combination with green-synthesized selenium nanoparticles (TFGE-SeNPs), against APAP-induced kidney damage in mice. Mice were divided into five groups (n=7 per each) as follows: Control group; APAP group: Mice received oral single APAP dose (3 g /kg); APAP + TFGE group: mice treated with oral single dose of APAP (3 g /kg) then administrated TFGE (250 mg/kg) for sequential 5 days; APAP + TFGE-SeNPs group: Mice orally received APAP (3 g/kg) then treated with TFGE-SeNPs (0.5 mg/kg) for 5 days; APAP + NAC group: Mice were given an oral dose of N-acetylcysteine (NAC, 200 mg/kg) for 5 days subsequently to stimulation of kidney toxicity by APAP. Results revealed that APAP exposure significantly elevated (p<0.05) serum urea, creatinine, neutrophil gelatinase-associated lipocalin (NGAL), kidney injury molecule-1 (KIM-1), while reducing (p<0.05) antioxidant markers (Reduced glutathione, Superoxide dismutase, Catalase, Glutathione peroxidase, and Glutathione reductase) and increasing (p<0.05) oxidative markers (Nitric oxide and Malondialdehyde). Treatment with TFGE-SeNPs effectively reversed these changes, restoring antioxidant balance and reducing renal injury markers (p<0.05). Moreover, TFGE-SeNPs modulated key molecular signals by upregulating (p<0.05) nuclear factor erythroid 2-related factor 2 (Nrf2) and downregulating (p<0.05) inducible nitric oxide synthase (iNOS) expression, attenuating inflammation and preserving renal histoarchitecture. In summary, TFGE-loaded SeNPs provided potent antioxidant and anti-inflammatory protection against APAP-induced nephrotoxicity, offering a promising nanotherapeutic strategy for kidney injury. • Acetaminophen (APAP) overdose induces nephropathy through multiple mechanisms. • Trigonellafoenum-graecum (TFG) prevents nephrotoxicity by suppressing oxidative stress, inflammation, and apoptosis. • PGs loaded with selenium nanoparticles are more potent than N -acetylcysteine (NAC) in treating APAP-induced nephrotoxicity. • TFG loaded with selenium nanoparticles provided potent antioxidant and anti-inflammatory protection against APAP-induced nephrotoxicity.