Effects of curcumin and nicorandil on nilotinib-induced QT interval prolongation in rats: A telemetry-based study
Pakistan Journal of Pharmaceutical Sciences, cilt.39, sa.10, ss.2991-3000, 2026 (SCI-Expanded, Scopus)
- Yayın Türü: Makale / Tam Makale
- Cilt numarası: 39 Sayı: 10
- Basım Tarihi: 2026
- Doi Numarası: 10.36721/pjps.2026.39.10.277.1
- Dergi Adı: Pakistan Journal of Pharmaceutical Sciences
- Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, EMBASE, MEDLINE, Biomedical Reference Collection: Corporate Edition (EBSCO)
- Sayfa Sayıları: ss.2991-3000
- Anahtar Kelimeler: Curcumin, KATP channels, Long QT syndrome, Nicorandil, Nilotinib
- Eskişehir Osmangazi Üniversitesi Adresli: Evet
Özet
Background: Long QT syndrome (LQTS) is characterized by QT prolongation, ventricular arrhythmias and sudden death. Nilotinib (Nilo), a tyrosine kinase inhibitor used in chronic myeloid leukemia, prolongs QTc mainly through hERG (IKr) channel inhibition. Curcumin (Curc), often co-administered, modulates cardiac ion channels, whereas nicorandil (Nico) acts as a KATP channel opener. Objectives: This study evaluated the effects of Curc and Nico on Nilo-induced QTc prolongation. Methods: Male Sprague–Dawley rats implanted with radiotelemetry transmitters received 10 mg/kg nilotinib (selected as the minimal effective dose based on preliminary dose-finding studies at 10, 30 and 50 mg/kg), 100 mg/kg curcumin, or 10 mg/kg nicorandil, as previously described. Animals were allocated into seven groups: Control, Nilo, Curc, Nico, Nilo+Curc, Nilo+Nico and Nilo+Curc+Nico. ECG, biochemical and histopathological analyses were performed. Data were analyzed using one-way ANOVA followed by Tukey’s post hoc test. Results: Nilotinib caused dose-dependent QTc prolongation, with 10 mg/kg as the minimal effective dose (p<0.001). Curcumin further exacerbated QTc prolongation, whereas nicorandil co-administration mitigated this effect. (p<0.001). Nilo also elevated TNF-α and TAS, which were attenuated in combination groups. Conclusion: Nilotinib-induced dose-dependent QTc prolongation was aggravated by curcumin, whereas nicorandil demonstrated a potential protective effect on drug-induced LQTS.