الفهرس 
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Abstract
Environmental pollution is a one of the most deleterious agents to the biological life. Industrialization offered additional hazards to the environment surrounding man and animals. Because of a wide distribution of the heavy metals throughout the earth crust, in air, soil, and water, as well as the remarkable environmental pollution, these heavy metals represent global problems that are a growing threat to the environment.
Manganese (Mn) is a one of these heavy metals that has bio-importance as trace elements and is essential for optimal cellular function. However, Mn is widely distributed in nature. So, Environmental exposure to Mn is also of great concern and constitutes major contaminants.
Manganese toxicity represents a serious health hazards in man and animals, where exceedingly high brain manganese concentrations are known to implicate in neurotoxicity as well as oxidative stress.
The brain is particularly susceptible to this excess manganese and accumulation and can cause a neurodegenerative disorders known as manganism.
So the Mn toxicity and its treatment clearly remain an important problem and in the spotlight of society. More attentions have been carried out for some chelating agents that have relative efficacy in counteracting the manganese intoxication.
Therefore, the aim of the present study is to shed some light on the potential effect (efficacy) of both chelating agents Para-aminosalicylic acid (PAS) and N-(2-hydroxyethyl) ethylene diamine triacetic acid (HEDTA) against MnCl2. 4 H2o-induced cytotoxicity and oxidative stress in brain tissues.
- In this study seventy five male weanling rats (PND 21) were used and divided into two groups as following:
- Group A: Includes 10 rats, received distilled water for 60 days and served as
(-ve) control group (C1).
- Group B: Includes 65 rats, received manganese in the form of Manganese chloride tetrahydrate via drinking water for 60 days in a concentration of 5 mg/ ml of MnCl2. Twenty four hours after cessation of Mn exposure, the rats divided into 5 subgroups as following:
B1: Subgroup B1: Includes 5 rats. They killed directly after cessation of Mn administration, and served as (+ve) control group (C2).
B2: Subgroup B2: Includes 15 rats. They received saline solution 0.9% intraperitoneally (I/P) for 4 weeks, and served as withdrwal group (C3).
B3: Subgroup B3: Includes 15 rats. They received PAS 200 mg / Kg b.w. s/c daily for 5 days/week for 4 weeks. (PAS prepared in a solution of 0.9% saline).
B4: Subgroup B4: Includes 15 rats. They received HEDTA 50 mg/ Kg b.w. I/P daily for 5 days/week for 4 weeks. (HEDTA prepared in a solution of 0.9% saline).
B5: Subgroup B5: Includes 15 rats. They received both PAS and HEDTA.
Twenty four hours after the last injection, rats were anesthetized then blood and tissue samples were collected.
- Blood samples were collected for estimation of Mn, Fe and Cu as well as for hematological studies.
- Rat brain was dissected from the skull, and various brain regions (cerebral cortex, cerebellum, medulla obelongata) were dissected and used for estimation of metals (Mn, Fe and Cu), biochemical parameters of oxidative stress and neurohistopathology.
Our study revealed that, animal groups treated with each chelating agent separately, recovered the neurotoxicity and oxidative stress induced by MnCl2. 4 H2o and that indicated by; significant improvement in enzymes activity (SOD, Catalase, ACHE and Glutathione peroxidase) as well as marked decrease in TBARS and Nitric oxide production as compared to MnCl2. 4 H2o treated group.
Estimation of metals concentrations (Mn, Cu, and Fe) in different brain regions homogenate indicated that, administration of each chelating agent separately were relatively adverse the effect of MnCl2. 4 H2o by decrease the Mn, iron concentration and increase Cu level in brain tissues while in blood sample Cu, iron concentration increased and Mn level decreased in comparable with MnCl2. 4 H2o treated group.
Haematological parameters (RBCs, WBCs, Hb and blood platelets and their related parameters) in chelating agents treated groups exhibited a significant improvement than MnCl2. 4 H2o treated one.
Histopathological investigations results in Mn-exposed group showed thrombosis in the blood vessel with perivascular cellular reaction, congestion, haemorrhage, neuronal degeneration with focal gliaosis and pyknosis of Purkenji cell layer.
Chelating agents somewhat reversed the adverse effect of Mn and showed more or less normal histological structure and some slides showed only congestion in the ependymal blood vessels and degeneration of few neuron.
Withdrawal group showed no improvement in most of the previous parameters where Mn induced irreversible damage to the brain tissues.