SINAPIC ACID AMELIORATES ARSENIC TRI-OXIDE INDUCED RENAL TOXICITY: POTENTIAL IMPLICATION OF NF-ΚB AND NRF2/HO-1 PATHWAY
Sinapic acid (SA), a polyphenolic compound found in various plants, is recognised for its anti-inflammatory, chemoprotective, antimutagenic, antioxidant, and anticancer properties.However, its impact on arsenic trioxide (ATO)-induced kidney toxicity remains unclear.This study seeks to investigate the chemoprotective mechanisms of SA against ATO-induced renal toxicity in rats.The animals were administered SA per os (20 and 40 mg/kg bw) while simultaneously receiving intraperitoneal injections of ATO (5 mg/kg bw) over 10 days.The changes in renal morphology were examined using light microscopy to assess any structural alterations.In addition, biochemical parameters were monitored to evaluate renal function.To understand the mechanisms involved, the antioxidant, oxidative stress, and pro-inflammatory indices were assessed in renal tissues.Furthermore, protein expression related to apoptosis (Bax, Caspase-3, Bcl-2), inflammation (NF-B), and antioxidant defence (Nrf2, HO-1) was quantified using Western blot analysis.Administration of ATO significantly elevated renal function markers, antioxidants, oxidative stress, inflammatory cytokines, and apoptotic indices in renal tissues.However, treatment with SA effectively reversed these changes, reducing pro-apoptotic proteins (Bax, Caspase-3) and NF-B, while increasing antiapoptotic proteins Bcl2, Nrf2, and HO-1.These results indicate that SA protects against ATO-induced nephrotoxicity by modulating Nrf2/HO-1 and apoptotic pathways implicated in inflammation, oxidative stress, and apoptosis.. RezumatAcest studiu a investigat mecanismele chemoprotectoare ale acidului sinaptic (SA) mpotriva nefrotoxicitii induse de trioxidul de arsen (ATO) la obolani.Animalele au primit SA pe cale oral (20 i 40 mg/kg), concomitent cu administrarea intraperitoneal de ATO (5 mg/kg) timp de 10 zile.Modificrile morfologice renale au fost analizate prin microscopie optic, iar parametrii biochimici au fost monitorizai pentru evaluarea funciei renale.De asemenea, au fost determinate nivelurile de stres oxidativ, inflamaie i activitate antioxidant n esutul renal.n plus, expresia proteinelor implicate n apoptoz ( Bax, Caspaza-3, Bcl-2), inflamaie (NF-B) i aprare antioxidant (Nrf2, HO-1) a fost analizat prin Western blot.Administrarea de ATO a determinat o cretere semnificativ a markerilor funciei renale, a stresului oxidativ, a citokinelor inflamatorii i a proteinelor pro-apoptotice.Tratamentul cu SA a ameliorat aceste efecte, reducnd expresia proteinelor pro -apoptotice (Bax, Caspaza-3) i a NF-B, i crescnd nivelurile proteinelor anti-apoptotice Bcl-2, Nrf2 i HO-1.
Authors
- Mohammad Raish (ORCID: https://orcid.org/0000-0002-6015-6125)
Publication Details
- Journal
- FARMACIA
- Published
- 2025-06-29
- DOI
- https://doi.org/10.31925/farmacia.2025.3.16
- Primary Topic
- Arsenic contamination and mitigation
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- King Saud University