Curcumin modulates multiple cell death, matrix metalloproteinase activation and cardiac protein release in susceptible and resistant Plasmodium berghei-infected mice
Biomed Pharmacother. 2021 Dec 8;146:112454. doi: 10.1016/j.biopha.2021.112454. Online ahead of print.
ABSTRACT
Pro-inflammatory signaling, cell death, and metalloproteinases activation are events in Plasmodium infection. However, it is not known if treatment with mefloquine (MF), and curcumin (CM) supplementation, will modulate these conditions. Malaria was induced in two different studies using susceptible (NK 65, study 1) and resistant (ANKA, study 2) strains of mouse malaria parasites (Plasmodium berghei) in thirty male Swiss mice (n = 5) in each study. Following confirmation of parasitemia, mice received 10 mL/kg distilled water (infected control), MF (10 mg/kg), MF and CM (25 mg/kg), MF and CM (50 mg/kg), CM (25 mg/kg) and CM (50 mg/kg). Five mice (not infected) were used as control. After treatment, the animals were sacrificed, serum obtained and liver mitochondria were isolated. Serum Tumour Necrosis Factor alpha (TNF-α), C-reactive protein (CRP), Interleukins-1 beta (IL-1β) and Interleukins-6 (IL-6) as well as caspases-3, 9 (C3 and C9), p53, serum troponin I (TI) and creatine kinase (CK), were assayed using ELISA techniques. Mitochondrial membrane permeability transition (mPT) pore opening, mitochondrial F0F1 ATPase activity, and lipid peroxidation (mLPO) were determined spectrophotometrically. Matrix metalloproteinases 2 (MMP-2) and 9 (MMP-9) expressions were determined using electrophoresis. CM supplementation (25 mg/kg) significantly decreased serum p53, TNF-α, CRP and IL-6 compared with MF. In the resistant model, CM prevented mPT pore opening, significantly decreased F0F1 ATPase activity and mLPO. MF activated caspase-3 while supplementation with CM significantly decreased this effect. Furthermore, MMP-2 and MMP-9 were selectively expressed in the susceptible model. Malarial treatment with mefloquine elicits different cell death responses while supplementation with curcumin decreased TI level and CK activities.
PMID:34894518 | DOI:10.1016/j.biopha.2021.112454