Methylene blue inhibits lumefantrine-resistant Plasmodium berghei

Abstract

Introduction: Chemotherapy still is the most effective way to control malaria, a major public health problem in sub-Saharan Africa. The largescale use of the combination therapy artemether-lumefantrine for malaria treatment in Africa predisposes lumefantrine to emergence of resistance. There is need to identify drugs that can be used as substitutes to lumefantrine for use in combination therapy. Methylene blue, a synthetic anti-methemoglobinemia drug, has been shown to contain antimalarial properties, making it a candidate for drug repurposing. The present study sought to determine antiplasmodial effects of methylene blue against lumefantrine-and pyrimethamine-resistant strains of P. berghei. Methodology: Activity of methylene blue was assessed using the classical four-day test on mice infected with lumefantrine-resistant and pyrimethamine-resistant P. berghei. A dose of 45 mg/kg/day was effective for testing ED90. Parasitemia and mice survival was determined. Results: At 45 mg/kg/day, methylene blue sustained significant parasite inhibition, over 99%, for at least 6 days post-treatment against lumefantrine-resistant and pyrimethamine-resistant P. berghei (p = 0.0086 and p = 0.0191, respectively). No serious adverse effects were observed. Conclusions: Our results indicate that methylene blue at a concentration of 45 mg/kg/day confers over 99% inhibition against lumefantrineand pyrimethamine-resistant P. berghei for six days. This shows the potential use methylene blue in the development of antimalarials against lumefantrine-and pyrimethamine-resistant parasites.

Epineural Methylene Blue Injection May Aid Localization of Digital Nerves in Dupuytren’s Surgery

“…Since MB has been used for multiple purposes in medicine [23][24][25][26] including also in vivo staining in surgical applications [20,21,27,28], and its half-life is approximately 24 h [33], no long-term side effects are expected. This was in line with our observation that no discoloration was visible in MB-injected nerves days after surgery.…”

“…We chose methylene blue (MB) as it is a commonly used stain with a wide range of therapeutic applications [23][24][25][26]. MB as a stain has already been successfully used in parotid [20], biliary [27], thyroid surgery [21], and gynecologic oncology [28]; however, in these studies, the dye was either administered intraductally [20,27], or the operation area was rinsed with the solution [21,28].…”

Astemizole-Methylene Blue Combination Therapy Reduces Monotherapy Adverse Effects in Balb/C Mice

“…Stock solutions of 1 mg/ml anhydrous methylene blue (Sigma, Germany) and astemizole (sourced from University of Cape Town's Department of Chemistry) were prepared as previously described by Nyirongo et al; Mwangi et al, [12,14]. Similarly, astemizole-methylene blue drug combinations in ratios of 1:3 and 3:1 were prepared and stored at 4 0 C until needed [12].…”

A biomimetic synthesis of stable gold nanoparticles derived from aqueous extract of Foeniculum vulgare seeds and evaluation of their catalytic activity

“…It is also utilized for staining tissues and body fluids during diagnosis and surgeries (American Pharmacists Association 2012). Moreover, it also has applications as anti-malarial agent and chemotherapeutic agent (Schirmer et al 2003;Mwangi et al 2016). Similarly, Rhodamine B, a fluorescent staining dye, has applications in the field of flow cytometry (Temmerman and Nickel 2009), fluorescence microscopy and ELISA tracer techniques (Shelley 1969;Forster et al 2012).…”