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Sharma et al. Zinc supplementation prevents against LPS induced neurotoxicity in rats

Figure 4: Representative figures are HE stained coronal sections of the brain showing the effect of prenatal zinc supplementation on cortex
of prenatally LPS treated (A) male pups and (B) female pups. Left side: ×10; right side: ×40. LPS: lipopolysaccharide

production of inducible NO synthase to produce NO levels of maternal and fetal liver at 3 h, 6 h and 16 h after
by (1) interfering with calcium-activated colmudulin LPS injection to pregnant mice was observed. Also,
[64]
function; (2) inhibiting NADPH dependent cytochrome a significant decrease in levels of GSH in prenatally
P-450; and (3) by binding to glutathione and other LPS treated mice pups and 4-month-old rats were
thiols to decrease nitric oxide synthase activity. [31] reported. [65,66] Studies showed therapeutic efficacy of
N-acetylcysteine, a potent anti-oxidant and precursor
Significant reduction in GSH levels were observed in of glutathione to attenuate LPS-induced white matter
both prenatally LPS treated male and female pups. injury and hypomyelination in the developing rat
Whereas in case of pups from zinc supplemented brain. Zinc was found to be effective in decreasing
[67]
mothers showed significantly increased GSH levels. oxidative stress via metallothionein by regulating
Glutathione system is important for cellular defense the secretion of pro-inflammatory cytokines and
[68]
against ROS. O and NO radicals, although they these metallothionein’s are strong scavengers of free
2-
cannot react directly with GSH, can oxidize GSH radicals. [69,70] In the present study only prenatally LPS
after undergoing intracellular redox reactions NO can treated female pups showed significant decrease in
react with O by radical-radical interaction forming the activity of catalase and SOD enzyme. However
2-
peroxynitrite (ONOO ), thus clearing and scavenging prenatal zinc supplementation was unable to restore
-
O in a diffusion limited rate. [61-63] ONOO is a strong the activity of both the enzymes.
-
2-
oxidizing agent, a reactive nitrogen species which
oxidizes GSH rapidly to GSSG and depletes intracellular Female pups were found to be more prone to ill
store of GSH. Similar results for glutathione system effects of prenatal LPS exposure as compared to male
have been previously reported as decrease in GSH pups. As suggested by Paris et al., more of anxiety
[71]
42 Neuroimmunology and Neuroinflammation ¦ Volume 4 ¦ March 21, 2017