Protective role of lithium in ameliorating the aluminium-induced oxidative stress and histological changes in rat brain

Abstract

This study was carried out to investigate the effects of lithium (Li) supplementation on aluminium (Al) induced changes in antioxidant defence system and histoarchitecture of cerebrum and cerebellum in rats. Al was administered in the form of aluminium chloride (100 mg/kg b.wt./day, orally) and Li was given in the form of Li carbonate through diet (1.1 g/kg diet, daily) for a period of 2 months. Al treatment significantly enhanced the levels of lipid peroxidation and reactive oxygen species in both the cerebrum and cerebellum, which however were decreased following Li supplementation. The enzyme activities of catalase, superoxide dismutase (SOD) and glutathione reductase (GR) were significantly increased in both the regions following Al treatment. Li administration to Al-fed rats decreased the SOD, catalase and GR enzyme activities in both the regions; however, in cerebellum the enzyme activities were decreased in comparison to normal controls also. Further, the specific activity of glutathione-s-transferase and the levels of total and oxidized glutathione were significantly decreased in cerebrum and cerebellum following Al treatment, which however showed elevation upon Li supplementation. The levels of reduced glutathione were significantly decreased in cerebrum but increased in cerebellum following Al treatment, which however were normalized upon Li supplementation but in cerebellum only. Apart from the biochemical changes, disorganization in the layers of cerebrum and vacuolar spaces were also observed following Al treatment indicating the structural damage. Similarly, the loss of purkinje cells was also evident in cerebellum. Li supplementation resulted in an appreciable improvement in the histoarchitecture of both the regions. Therefore, the study shows that Li has a potential to exhibit neuroprotective role in conditions of Al-induced oxidative stress and be explored further to be treated as a promising drug against neurotoxicity.

Fig. 1

A section of cerebrum from normal control rat showing the histoarchitecture of cerebrum with pia matter, molecular layer and pyramidal layer (10×)

Fig. 2

A section of cerebrum from Al-treated rat showing the disorganization of cortical layers, vacuoles can be seen around the cells (10×)

Fig. 3

A section of cerebrum from Al-treated rats at higher magnification (40×) showing vacuolar spaces around the pyramidal cells

Fig. 4

A section of cerebral cortex of Al + Li-treated rats showing an improvement in the histoarchitecture and organized layers (10×)

Fig. 5

Cerebellum section from the normal control animals showing the well-organized molecular layer, purkinje cells layer and granular layer (10×)

Fig. 6

Cerebellum section from the Al-treated animal showing a loss of purkinje cell layer and a disorganization of granular layer (10×)

Fig. 7

Cerebellum section at higher magnification showing the loss of purkinje cells (40×)

Fig. 8

Cerebellum section from Al + Li-treated animal showing an improvement in the histoarchitecture showing molecular layer, purkinje cells layer and granular layer (10×)