Nephroprotective Effect of Methanolic Extract of Micromeria frivaldszkyana (Degen) Velen Against Acetaminophen Overdose in Rats

Acetaminophen (APAP) overdose can induce potentially fatal nephrotoxicity. <i>Micromeria frivaldszkyana</i> (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 <i>M. frivaldszkyana</i> in an APAP-induced rat model of kidney injury. The aim of the study was to investigate the protective potential of orally administered <i>M. frivaldszkyana</i> methanolic extract against APAP-induced nephrotoxicity. Male Wistar rats received a one-week treatment with saline, <i>M. frivaldszkyana</i> 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, <i>p</i> < 0.05), creatinine (59.51 ± 2.30 vs. 72.27 ± 3.92, <i>p</i> < 0.05), and uric acid (477.55 ± 52.48 vs. 898.33 ± 65.30, <i>p</i> < 0.001), while restoring renal glutathione (GSH) levels (4.43 ± 0.19 vs. 2.64 ± 0.10, <i>p</i> < 0.001) and catalase activity (3802.78 ± 142.05 vs. 2485.03 ± 143.23, <i>p</i> < 0.01), compared with APAP-treated rats. Malondialdehyde levels were significantly reduced by the extract (25.19 ± 0.95 vs. 69.66 ± 4.11, <i>p</i> < 0.001), with similar effects observed across all tested doses. In conclusion, <i>M. frivaldszkyana</i> 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.