Niprisan (Nix‐0699) improves the survival rates of transgenic sickle cell mice under acute severe hypoxic conditions

Abstract

Summary. The substitution of glutamic acid by valine at the sixth position of the beta-globins of haemoglobin S (Hb S) causes a drastic reduction in the solubility of the deoxy form of Hb S. Under hypoxic conditions, deoxy-Hb S molecules polymerize inside the cells, forming rigid, sickled cells. We studied the effect of Niprisan (Nix-0699), a naturally occurring antisickling agent, on the survival of transgenic (Tg) sickle mice under severe acute hypoxic conditions (60 min). Before hypoxia exposure, the mice were treated by gavage once daily for 7 d with 0 mg/kg (n ¼ 10), 10 mg/kg (n ¼ 5), 50 mg/kg (n ¼ 5), 300 mg/kg (n ¼ 4) or 500 mg/kg (n ¼ 5) of Nix-0699. The mean survival times of the untreated and treated mice were 10, 25, 39, 55 or 60 min respectively. The percentage of sickled cells in the venous blood of the treated mice was lower than that in control mice and was dose dependent. Histological examination of the lungs of the control mice showed entrapment of massive numbers of sickled cells in the alveolar capillaries, although the degree of such entrapment decreased with the increased dose of Nix-0699. Nix-0699 may be a promising option for the treatment and management of patients with sickle cell disease.

Effects of Athrospira Platensis, Monodora Myristica and Helianthus Annuus on the Rate of Polymerization, Sickle Cell Reversion and Oxygen Affinity of Sickle Cell Hemoglobin

“…Among the various potential antisickling agents tested, hydroxyurea (HU) has been the most effective compound used for the treatment of patients with sickle cell disease (SCD). NIPRISAN (Nix-0699), an ethanol/water extract from indigenous plants, has a strong antisickling effect 14 . The kinetics of polymerization on addition of 0.05 microgram/ml Nix-0699 caused a six-fold prolongation of the delay time prior to deoxy-Hb S polymerization when compared with that of untreated Hb S samples [14][15][16] .…”

“…NIPRISAN (Nix-0699), an ethanol/water extract from indigenous plants, has a strong antisickling effect 14 . The kinetics of polymerization on addition of 0.05 microgram/ml Nix-0699 caused a six-fold prolongation of the delay time prior to deoxy-Hb S polymerization when compared with that of untreated Hb S samples [14][15][16] . Expressed anti-sickling activity on the inhibition is comparable to the findings of Platt 17 .…”

Phyto-Medicine in Gene(s) Targeting Future Direction for Sickle Cell Disease Management

“…Further analysis and efficacy test on SCD patients, using Nicosan showed effective sickling reversal [11,34,39,40].…”

“…Hemoglobin content of their blood is half the normal value of 15-16 g/100 mL. Sometimes these HbS red blood cells become sickle-shaped with difficulty passing through small blood vessels, such as capillaries (site of gaseous exchange), causing severe pains and interference with normal organ function which is a major crux in early death of people with the SCD phenotype [11].…”

“…People with SCD are homozygous for the sickle cell allele [11,12] and have red blood cells containing mostly HbS, an abnormal type of Hb. Hemoglobin content of their blood is half the normal value of 15-16 g/100 mL.…”