Differential induction of oxidative impairments in brain regions of male mice following subchronic consumption of Khesari dhal ( Lathyrus sativus) and detoxified Khesari dhal

Abstract

Neurolathyrism is a neurodegenerative disease caused by the chronic consumption of Khesari dhal ( Lathyrus sativus L). It is generally accepted that β- N-oxalylamino- l-alanine (b-ODAP), a non-protein amino acid present in the seeds is the primary causative agent. Based on in vitro studies with β-ODAP, both excitotoxic and oxidative stress mechanisms have been speculated to be responsible for its neurotoxic effects. However, occurrence and the involvement of oxidative stress mechanisms in experimental animals following Khesari dhal consumption in vivo is less well understood. Accordingly in the present study, we have addressed primarily two questions: (i) whether dietary intake of Khesari dhal (KD) causes oxidative impairment in specific regions of brain, such as cortex and cerebellum and (ii) if there is any significant reduction in the oxidative damage induction following consumption of detoxified Khesari dhal (DKD). Adult male mice were fed either normal, KD or DKD incorporated diet (30%) for a period of 4 or 12 weeks. Biochemical markers of oxidative stress, such as lipid peroxidation (LPO), generation of reactive oxygen species (ROS), activity of antioxidant enzymes, protein carbonyls in brain regions (cortex, cerebellum) were determined. Mice fed KD diet showed enhanced LPO levels and ROS generation in brain, while the levels of LPO and ROS were unaltered in DKD mice. Interim sampling (4 weeks) also showed a similar trend though the degree of oxidative damage was lower. Depletion of reduced GSH, significant alterations in the activity of various antioxidant enzymes and enhanced protein carbonyls in brain in KD fed mice suggested that a state of oxidative stress exists in vivo. Interestingly, no significant induction of oxidative damage was evident in the brain of mice fed DKD. However, altered cholinergic function was discernible among both treatment groups. KD consumption resulted in a marked reduction of brain AChE activity at both sampling times (cortex, 38–43%; cerebellum, 22–41%), while DKD consumption resulted in less robust reduction (cortex, 11–17%; cerebellum, 11–13%). Taken together, these data suggest that dietary KD has the propensity to induce marked oxidative damage in brain of male mice, while DKD failed to induce any significant degree of oxidative impairments. Based on these results, it is hypothesized that oxidative stress mechanisms may wholly or in part contribute towards the development of neuro-degeneration associated with human consumption of L. sativus.