Kolaviron Mitigates Bilirubin-induced Neocortical Oxidative Damage and Neuroinflammation in Young Wistar Rats

Oxidative stress and neuroinflammation play a central role in the pathogenesis of numerous neurological disorders  by disrupting cellular redox balance and promoting neuronal degeneration. Phenylhydrazine (PHZ), a well established inducer of oxidative stress and hemolytic anemia, generates reactive oxygen species capable of causing  structural and functional damage to the brain. Kolaviron, a biflavonoid complex isolated from Garcinia kola seeds,  possesses potent antioxidant and neuroprotective properties. However, its effects on PHZ-induced neocortical  oxidative stress and neuroinflammation remain poorly understood. Twelve adult female Wistar rats were assigned  into three groups (n = 4 per group) and allowed to breed. Hyperbilirubinemia was induced in neonatal pups using  phenylhydrazine (75 mg/kg body weight, intraperitoneally), while 200 mg/kg of Kolaviron was administered  orally to the mothers from postnatal day 1 to day 14.  At the end of the experimental period, animals were  euthanized, and neocortical tissues were harvested for biochemical assays of catalase, superoxide dismutase  (SOD), and interleukin-1β (IL-1β), and histological evaluation. PHZ significantly altered antioxidant enzyme  activities, evidenced by reduced catalase and SOD activities, while significantly elevating the concentration of  pro-inflammatory cytokine IL-1β. However, KV regulated the concentrations of these biomarkers similar to the  control. Histological examination of the cerebral neocortex also revealed varying degrees of alterations. The  findings of this study demonstrate that phenylhydrazine induces oxidative stress, neuroinflammation, and mild  neocortical neurodegeneration, while kolaviron effectively attenuates these alterations through its antioxidant and  anti-inflammatory activities. 

Key Words: Kolaviron, phenylhydrazinium chloride/phenylhydrazine, oxidative stress, neuroinflammation,  neocortex