The following work describes the development of a novel noninvasive transmucosal drug delivery system, the chitosan sponge matrix (CSM). It is composed of cationic chitosan (CS) nanoparticles (NPs) that encapsulate cisplatin (CDDP) embedded within a polymeric mucoadhesive CS matrix. CSM is designed to swell up when exposed to moisture, facilitating release of the NPs via diffusion across the ma...

For antimalarial 8-aminoquinoline (8-AQ) drugs, the ionization potential (energy required to remove an electron) of their putative metabolites has been proposed to be correlated in part to their hemotoxicity potential. NPC1161 is a developmental candidate as an 8-AQ antimalarial drug. In this work, the ionization potentials (IPs) of the S-NPC1161 (NPC1161a) hydroxylated derivatives, which are p...

INTRODUCTION Hemolytic anemia, the early removal of erythrocytes from the circulation, has been recognized as a side effect of drugs and other environmental chemicals. Formation of methemoglobin (MetHb) following chemical exposure is the first hemotoxic response in the induction of hemolytic anemia. The purpose of this study was to compare the species differences in the chemical induction of Me...

The study evaluated the ameliorative effect of vitamin C on chronic chlorpyrifos-induced hematological alterations in Wistar rats. Twenty adult male rats divided into 4 groups of 5 animals each were exposed to the following regimens: group I (S/oil) was administered soya oil (2 mL/kg b.w.), while group II (VC) was given vitamin C (100 mg/kg b.w.); group III was dosed with CPF (10.6 mg/kg b.w.);...

In this study, we determined in vivo interactions between hemopoietic growth factors and etoposide (VP-16) to assess whether normal blood cell production could be maintained during chemotherapy if hemopoietic growth factors were simultaneously administered. Groups of mice were treated for 7 consecutive days with four different doses of VP-16 in combination with three different doses of erythrop...

Primaquine-induced hemolytic anemia is a toxic side effect that is due to premature splenic sequestration of intact erythrocytes. Previous studies have suggested that a phenolic metabolite, 5-hydroxyprimaquine (5-HPQ), mediates primaquine hemotoxicity by generating reactive oxygen species (ROS) within erythrocytes that overwhelm antioxidant defenses. However, the nature of the oxidative stress ...

BACKGROUND Patients with colorectal cancer treated with oxaliplatin are at risk of hypersensitivity reactions, with the incidence estimated to be 12%-20%. Coinfusion of dexamethasone and oxaliplatin could potentially reduce the incidence of these reactions, but oxaliplatin is reported to be incompatible with alkaline compounds in solution. However, in a previous retrospective study we found tha...

Favism is an acute anemic crisis that can occur in susceptible individuals who ingest fava beans. The fava bean pyrimidine aglycone divicine has been identified as a hemotoxic constituent; however, its mechanism of toxicity remains unknown. We have shown recently that divicine can induce a favic-like response in rats and that divicine is directly toxic to rat red cells. In the present study, we...

Our previous analysis of antiplasmodial properties exhibited by dodecanoyl-based oligo-acyl-lysyls (OAKs) has outlined basic attributes implicated in potent inhibition of parasite growth and underlined the critical role of excess hydrophobicity in hemotoxicity. To dissociate hemolysis from antiplasmodial effect, we screened >50 OAKs for in vitro growth inhibition of Plasmodium falciparum strain...

Development of anti-cancer drugs towards clinical application is costly and inefficient. Large screens of drugs, efficacious for non-cancer disease, are currently being used to identify candidates for repurposing based on their anti-cancer properties. Here, we show that low-dose salinomycin, a coccidiostat ionophore previously identified in a breast cancer screen, has anti-leukemic efficacy. AM...