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Hydrophobic NADES-Derived Pumpkin Carotenoid Extract Attenuates Oxidative Stress and Mitochondrial Dysfunction in a
Milana Bosanac1, Bojana Andrejić Višnjić1, Aleksandra Popović2
1Department of Histology and Embryology, Faculty of Medicine, University of Novi Sad, 21000 Novi Sad, Serbia.
Abstract:
Background/Objectives: Doxorubicin-induced cardiotoxicity (DIC) is driven by oxidative stress and impaired oxidative phosphorylation (OXPHOS). Antioxidant properties of carotenoids in vivo depend on extraction, while their direct role in mitigating DIC remains undetermined. This study evaluated the cardioprotective potential of natural deep eutectic solvents (NADES)-derived pumpkin carotenoid extract in a rat model of DIC. Methods: NADES-derived pumpkin pulp extract was characterized by spectrophotometry and HPLC-DAD. Wistar rats (n = 30) were assigned to six groups: C (control), N (NADES, 1 mL, p.o.), P (extract, 900 µg/kg body weight/day of total carotenoids, p.o.), D (doxorubicin, four i.p. doses, 2 mg/kg), ND (NADES/doxorubicin) and PD (900 µg/kg body weight/day of total carotenoids/doxorubicin). The activity of antioxidant enzymes and mitochondrial respiration in saponin-permeabilized left ventricular fibers using a Clark-type oxygen electrode) was measured. Results: Compared to control, cardiac antioxidant enzyme activities, mitochondrial respiration in complex I-linked respiration, ADP-supported OXPHOS, maximal respiratory capacity, and complex II and IV-linked respiration were significantly impaired by doxorubicin and unaltered by NADES. Co-administration of the extract significantly improved antioxidant enzyme activities (GSH-Px: D group 45 vs. PD group 95 nmol/mg proteins; GR: D group 95 vs. PD group 145 nmol/mg proteins; GST: D group 15 vs. PD group 22 nmol/mg proteins; SOD: D group 9 vs. PD group 17 U/mg proteins) and attenuated mitochondrial respiratory dysfunction compared with doxorubicin-treated group, indicating partial preservation of electron transport system capacity. Conclusions: Despite limitations of the study (single sex, single dose), results suggest NADES-based carotenoid extracts have cardioprotective properties in DIC by enhancing antioxidant defenses and supporting mitochondrial respiration.
Insights
Natural deep eutectic solvent-derived pumpkin carotenoids protect against doxorubicin-induced cardiotoxicity by boosting antioxidant defenses and supporting mitochondrial function in rats.
Area of Science:
- Cardiology
- Biochemistry
- Pharmacology
Background:
- Doxorubicin-induced cardiotoxicity (DIC) stems from oxidative stress and impaired mitochondrial oxidative phosphorylation (OXPHOS).
- The in vivo antioxidant efficacy of carotenoids is extraction-dependent, and their direct role in mitigating DIC is unclear.
- This study investigates the cardioprotective effects of pumpkin carotenoids extracted using natural deep eutectic solvents (NADES) in a rat model of DIC.
Purpose of the Study:
- To evaluate the cardioprotective potential of NADES-derived pumpkin carotenoid extract against doxorubicin-induced cardiotoxicity in Wistar rats.
- To assess the impact of the extract on cardiac antioxidant enzyme activities and mitochondrial respiration.
- To determine if NADES-based carotenoid extracts can mitigate DIC by enhancing antioxidant defenses and supporting mitochondrial function.
Main Methods:
- Pumpkin pulp extract was characterized using spectrophotometry and HPLC-DAD.
- Wistar rats were divided into six groups: control, NADES, extract, doxorubicin, NADES/doxorubicin, and extract/doxorubicin.
- Cardiac antioxidant enzyme activities and mitochondrial respiration (complex I-linked, II-linked, IV-linked, and ADP-supported OXPHOS) were measured in saponin-permeabilized left ventricular fibers.
Main Results:
- Doxorubicin significantly impaired cardiac antioxidant enzyme activities and mitochondrial respiration, while NADES alone had no effect.
- Co-administration of the NADES-derived pumpkin carotenoid extract significantly improved antioxidant enzyme activities (GSH-Px, GR, GST, SOD) compared to the doxorubicin group.
- The extract attenuated doxorubicin-induced mitochondrial respiratory dysfunction, partially preserving electron transport system capacity.
Conclusions:
- NADES-based carotenoid extracts demonstrate cardioprotective properties in doxorubicin-induced cardiotoxicity.
- These protective effects are mediated by enhanced antioxidant defenses and improved mitochondrial respiration.
- Further research is warranted, acknowledging study limitations such as single sex and single dose.
