ANTI-PLASMODIAL EFFECT OF NICOTINAMIDE- VITAMIN B3 AGAINST CHLOROQUINE RESISTANT MALARIA IN AN IN VIVO MODEL

Nicotinamide (NICO), an amide derivative of nicotinic acid, used in high doses for four decades, has shown antimicrobial and potential anti-malarial activity in vitro. However, its antiplasmodial effects in drug-resistant in vivo models were previously unexplored.Our study explored the antimalarial impact of Nicotinamide (NICO) in chloroquine-resistant malaria mouse models. We administered NICO at doses from 1.82 mg/kg to 4.55 mg/kg body weight, beginning 72 hours post-infection and continuing until 7th day. On the 8th day, all animals were euthanized, and blood and organs were collected for experiments.When administered alone, NICO reduced parasitemia by 88%, which further reduced to 95.27% when combined with chloroquine (65 mg/kg body weight). Plasmodium-specific 18S rRNA analysis via RT-PCR in liver confirmed reduced parasitemia with Nicotinamide aloneand in combination with chloroquine. Liver pathology scores significantly improved with the high NICO dose (4.55 mg/kg body weight, p=0.012) and its combination with chloroquine (65 mg/kg body weight, p<0.0001) compared to untreated chloroquine-resistant mice. Intracellular Reactive Oxidative Species (ROS) levels in liver lymphocytes and serum Nitric Oxide (NO) levels were notably reduced with combination therapy (p<0.001, p<0.0001, respectively). Our study demonstrates NICOs antimalarial potential alone and its synergistic effect with chloroquine, offering promise against chloroquine-resistant malaria.