PROTECTIVE EFFECT OF ASCORBIC ACID AND TIRON (4-5 DIHYDROXY- 1, 3 BENZENDISULFONIC ACID) AGAINST MERCURY CHLORIDEINDUCED OXIDATIVE STRESS AND NEUROTOXICITY IN RABBIT

The current study was performed to assess the potential of 4-5 dihydroxy-1, 3
benzendisulfonic acid (Tiron) and L-ascorbic acid (vitamin C) against inorganic mercury
(mercuric chloride-HgCl2) induced oxidative stress and neurotoxicity in female New
Zealand white rabbits. 10 rabbits per group were assigned to one of four treated groups: 0
mg HgCl2, 0 mg Ascorbic acid and 0 mg Tiron (control); 1mg Hg Cl2/kg BW orally; 1mg
HgCl2/kg BW orally plus 1gm ascorbic acid /liter in drinking water; HgCl2/kg BW orally
plus 471mg Tiron/kg BW I/P. Rabbits were administered HgCl2 and ascorbic acid for three
months while Tiron administered in 6 concessive doses for 15 days at the level of three
doses per week. Biochemical analyses on oxidative stress-related parameters and
acetylcholine esterase activity as neurotransmitter were carried out. Histopathological
analyses for detecting the cellular damage in brain tissues of exposed rabbits were also
performed. Results obtained showed that HgCl2 significantly (p < 0.05) increased
malondialdehyde and 4-hydroxyalkenals (MDA&4-HAE the marker of lipid oxidation)
in brain tissues, while the activities of superoxide dismutase (SOD), Glutathione
peroxidase (GSHPx) and acetylcholine esterase (AChE) activities were significantly
(p < 0.05) decreased. Histopathological analysis of the brain revealed that neuronal
degeneration with apoptotic features in cerebral cortex, hippocampus and cerebellum. Loss
and significant (p < 0.05) decrease of purkinje cells number in cerebellum was detected.
Also the purkinje cells lost the normal shape and became distorted. Most of the above
parameters responded positively with either Tiron or vitamin C therapy, but more
pronounced beneficial effects on the previous described parameters were observed in Tiron
treated group. It is concluded that the protective effect of vitamin C as antioxidant and
Tiron as a chelating agent against mercury chloride - induced neurotoxicity. Tiron was
more effective than vitamin C in restoration of the most investigated parameters.