Abstract
Acetaminophen (APAP) overdose can induce potentially fatal nephrotoxicity. Micromeria frivaldszkyana (M. frivaldszkyana), an endemic plant to Bulgaria, has demonstrated significant antioxidant activity. This study represents the first evaluation of the nephroprotective effects of a methanolic extract of M. frivaldszkyana in an APAP-induced rat model of kidney injury. The aim of the study was to investigate the protective potential of orally administered M. frivaldszkyana methanolic extract against APAP-induced nephrotoxicity. Male Wistar rats received a one-week treatment with saline, M. frivaldszkyana extract (250, 400, or 500 mg/kg), rosmarinic acid (100 mg/kg), or silymarin (125 mg/kg). On day 7, renal injury was induced by oral administration of APAP (2000 mg/kg). Forty-eight hours later, blood and kidney samples were collected for biochemical and histological analyses. The extract at 500 mg/kg significantly reduced the elevated levels of serum urea (1.83 ± 0.24 vs. 3.49 ± 0.75, p < 0.05), creatinine (59.51 ± 2.30 vs. 72.27 ± 3.92, p < 0.05), and uric acid (477.55 ± 52.48 vs. 898.33 ± 65.30, p < 0.001), while restoring renal glutathione (GSH) levels (4.43 ± 0.19 vs. 2.64 ± 0.10, p < 0.001) and catalase activity (3802.78 ± 142.05 vs. 2485.03 ± 143.23, p < 0.01), compared with APAP-treated rats. Malondialdehyde levels were significantly reduced by the extract (25.19 ± 0.95 vs. 69.66 ± 4.11, p < 0.001), with similar effects observed across all tested doses. In conclusion, M. frivaldszkyana methanolic extract confers significant protection against APAP-induced nephrotoxicity, likely through antioxidant-mediated mechanisms, enhanced GSH restoration, and attenuation of lipid peroxidation, highlighting its potential as a nephroprotective agent.