Malaria is a vector-transmitted disease prevalent in tropical and subtropical areas of the world. There were an estimated 608,000 deaths worldwide, with the majority occurring in the African region, where more than 249 million cases were reported (World Health Organisation, 2024). Serious complications often ensue, especially in the absence of prompt diagnosis and appropriate treatment (Mazen and Andrew, 2017). It is a severe and frequently fatal illness with significant global health consequences. As per the latest World Malaria Report, approximately 50 % of the global population resides in regions where malaria transmission is a potential threat, spanning 85 nations and territories (CDC, 2024). Oxidative stress and inflammation contribute to the pathophysiology of malaria infection (Vasquez et al., 2021). Reactive oxygen species (ROS) are produced in this process (Iwalokun et al., 2006). This can occur when the parasite invades the host or when the host's immune system reacts to the infection (Percário et al., 2012; Kavishe et al., 2017). The ROS generated during malaria are accountable for the numerous complications in severe malaria (Mohanty et al., 2021), as they can induce oxidative damage and cause cellular harm to vital organs (Mazen and Andrew, 2017).

Inflammation has been linked to oxidative stress in various diseases (Subra, 2016), with OGG1 activity being implicated in numerous inflammatory related pathological conditions (Ba et al., 2014; Hanna et al., 2020; Zhang et al., 2023). Specific examples include the involvement of OGG1 in the pathogenesis of viral infections (Fan et al., 2023), asthma (Ba et al., 2015), and pulmonary disease (Ma et al., 2022) among others. Base excision repair of 7,8-dihydro-8-oxoguanine (8-oxoG) during oxidative DNA damage is catalysed by the OGG1 (Aguilera-Aguirre et al., 2014), thus, making this enzyme a crucial target for therapeutic intervention in many inflammatory-associated conditions. Previous studies have shown that modulating its activity could significantly impact therapeutic strategies in various diseases such as Pseudomonas aeruginosa infection (Qin et al., 2020), breast cancer (Baquero et al., 2022), African swine fever virus infection (Fan et al., 2023), acute pancreatitis (Hajnády et al., 2022), allergic asthma (Tanner et al., 2022), respiratory syncytial virus infection (Zheng et al., 2022a), polycystic ovarian syndrome (Xia et al., 2022), and lung fibrosis (Tanner et al., 2023). However, the potential of OGG1 inhibition in other inflammatory diseases like malaria, tuberculosis, and meningitis remains unexplored (Samaila et al., 2024).

Evidence from previous studies have shown a strong association between oxidative stress and inflammation and the crucial role of 8-OxoG/OGG1 pathway in regulating the pro-inflammatory genes. Oxidative stress is an important part of malarial pathophysiology and could be one of the key factors of severe inflammation seen during malaria. Targeting 8-OxoG/OGG1 pathway by suppressing the activity of OGG1 during malaria infection might reduce severe inflammation and therefore represent a promising strategy in the effort of combatting the disease. So, it is noteworthy to suggest that OGG1 is involved during malaria and suppressing its activity can have a positive impact and potentially serve as an adjuvant therapeutic intervention in malaria. Therefore, this study aimed to explore the potential of targeting OGG1 during malaria infection by modulating its activity, specifically to determine the effect of suppressing OGG1 activity on the severity, survival and histopathological features of P. berghei infected mice.