Polypharmacological neurotoxic effects of methylisothiazolinone revealed by integrated in vitro and network-based chemoinformatics approaches
Journal of Toxicological Sciences, cilt.51, sa.9, ss.471-487, 2026 (SCI-Expanded, Scopus)
- Yayın Türü: Makale / Tam Makale
- Cilt numarası: 51 Sayı: 9
- Basım Tarihi: 2026
- Doi Numarası: 10.2131/jts.51.471
- Dergi Adı: Journal of Toxicological Sciences
- Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, BIOSIS, Chimica, EMBASE, MEDLINE, Academic Search Ultimate (EBSCO), Natural Science Collection (ProQuest), Biomedical Reference Collection: Corporate Edition (EBSCO)
- Sayfa Sayıları: ss.471-487
- Anahtar Kelimeler: Apoptosis, Chemoinformatics studies, Methylisothiazolinone, Neuroinflammation, Neurotoxicity
- Açık Arşiv Koleksiyonu: AVESİS Açık Erişim Koleksiyonu
- İstanbul Üniversitesi Adresli: Evet
Özet
Methylisothiazolinone (MIT) is a widely used biocidal preservative in industrial and cosmetic products. However, evidence of its neurotoxic effects is limited, and the mechanistic pathways are poorly defined. This study investigated the neurotoxic potential of MIT and the molecular mechanisms underlying its cellular toxicity in SH-SY5Y cells. After exposing SH-SY5Y cells to MIT various concentrations (30 to 120 μM) for 24 hr, apoptosis and inflammatory responses were quantified alongside the determination of apoptotic-, oxidative stress-, cell survival-, and angiogenic-related biomarkers. To reinforce the experimental findings, a set of in silico chemoinformatics studies, including network toxicology and molecular docking were conducted to pinpoint and evaluate the potential molecular targets of MIT. The IC50 value of MIT was found 115 μM. Total apoptotic cells increasing to 56.5% at 120 μM. ELISA results indicated activation of the intrinsic apoptotic pathway, evidenced by significant upregulation of p53 (9.54-fold), BAX (4.52-fold), and APAF-1 (8.85-fold), along with a disruption in the BAX/BCL-2 (4.52/4.37-fold) balance. Furthermore, an elevation in the COX/COX-2 (8.04/6.93-fold), SRC (7.08-fold), and VEGFR2 (20.96-fold) levels which indicated the concurrent oxidative stress and stress-induced pro-survival signaling at 120 μM. MIT selectively amplified some inflammatory mediators, suggesting inflammasome-driven neuroinflammation. In silico analysis further support MIT as a polypharmacological toxicant with the potential to modulate key molecular targets, including PARP-1, GSK-3β, and iNOS. MIT induced multifaceted neurotoxicity in SH-SY5Y cells through the simultaneous activation of intrinsic apoptotic signaling, oxidative stress, and selective neuroinflammatory pathways. The findings emphasize the potential neurotoxic risks associated with MIT exposure and underscore the necessity for strengthened regulatory evaluation and in vivo validation.