Niacin enhances erythropoiesis and attenuates oxidative stress and ferroptosis through the modulation of Nrf2/HO-1/GPX4 pathway in phenylhydrazine-induced hemolytic anemia in rats.

Anemia is a public health issue affecting people of all ages worldwide. 43% of children under five in Egypt are suffering from anemia. Hemolytic anemia (HA), characterized by the premature destruction of red blood cells, is often associated with oxidative stress. Phenylhydrazine (PHZ) is a chemical substance frequently used to induce HA in experimental animal models. Studies indicate that niacin (nicotinic acid) activates antioxidant pathways through nuclear factor erythroid 2-related factor 2 (Nrf2). This study aimed to evaluate the antianemic effects of niacin in PHZ-induced hemolytic anemia in rats. Twenty-four rats were divided into four groups (n=6). The control group received saline for two days, then 5% CMC. The anemia group received PHZ (40 mg/kg/day, i.p.) for two days, followed by 5% CMC. The low- and high-dose niacin groups received PHZ for two days, then niacin (100 or 360 mg/kg/day, orally) for six days. Niacin-treated groups showed hematological parameters close to normal levels, affected the expression of Nrf2/ARE genes, preserved histological architecture, and reduced caspase-3 protein expression. Niacin protected rats from hemolytic anemia by restoring blood parameters and promoting red blood cell survival. It may serve as a potential treatment by reducing oxidative stress, ferroptosis, and inflammation, while supporting erythropoiesis.