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Ebenezer OO, Curcumin modulates multiple cell death, matrix metalloproteinase.pdf (2.67 MB)

Curcumin modulates multiple cell death, matrix metalloproteinase activation and cardiac protein release in susceptible and resistant plasmodium berghei-infected mice.

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posted on 2023-02-21, 09:29 authored by John O. Olanlokun, Wisdom Oshireku Abiodun, Oluwakemi Ebenezer, Neil A. Koorbanally, Olufunso Olabode Olorunsogo

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 mito?chondria 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 cre?atine kinase (CK), were assayed using ELISA techniques. Mitochondrial membrane permeability transition (mPT)  pore opening, mitochondrial F0F1 ATPase activity, and lipid peroxidation (mLPO) were determined spectro?photometrically. 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.  

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