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Abstract It is concluded from the present study that: 1. Oral administration of lead acetate in drinking water for six weeks resulted in severe damages of the histological sections of liver, kidney, spleen, stomach, intestine and testis of male albino rats. Impaired oxidant/antioxidant balance may be responsible for the toxic effects of lead. 2. The co-administration of DMSA with lead acetate reduced the toxic effect of lead in all the histological sections of the tissues used in the present study. The chelating action of DMSA for lead may be responsible for reducing the cellular toxicity of lead. 3. The co-administration of lead acetate with both vitamin C and vitamin E resulted in an improvement of the histopathological changes that are induced by lead acetate. This improvement may be due to the antioxidant activity of vitamins C and E which protect the cells from oxidative stress and used in the treatment of lead toxicity in soft organs. 4. The administration of lead acetate combined with DMSA and both vitamins C and E overcome the histopathological changes that are produced by lead acetate in liver, kidney, spleen, stomach, intestine and testis of albino rats in the present study. It is known that DMSA acts as a chelating agent of lead in soft tissues, and vitamins C and E acts as antioxidant which prevent the generation of reactive oxygen species (ROS) and alternation of antioxidant defense system in animals as a result of exposure to lead. Hence, DMSA as a chelating agent for lead and vitamins C and E caused stoppage of oxidative stress by its Conclusion and Summary 106 antioxidant activities and restore the normal histological pictures of organs examined in the present study. Summary Lead is one of the most abundant heavy metals on the earth. It has been widely used throughout human history, posing a serious health problem to susceptible populations and animals. It induced many biological effects on animals and humans. Lead toxicity includes damage to soft tissues, such as liver, kidney, spleen, gastrointestinal tract and reproductive system. The adverse effects of lead on the histological sections of the organ used in the present study may be mediated by oxidative damage and subsequent lipid peroxidation. DMSA is a chemical derivative of dimercaptol. It contains two sulfhydryl (-SH) groups and has been shown to be an effective chelator of toxic metals mainly lead and arsenic. For major advantages of DMSA include its low toxicity, oral administration and no redistribution of metal from one organ to another. DMSA has been tried successfully in animals. Animal studies suggest that DMSA is an effective chelator of heavy metals in soft tissues. Vitamin C is a water-soluble antioxidant occurring in the organism as an ascorbic anion. It also acts as a scavenger of free radicals and plays an important role in the regeneration of α-tocopherol. Vitamin E (α-tocopherol) is a fat-soluble vitamin known to be one of the most endogenous antioxidants. α- tocopherol is a term that encompasses a group of potent, lipid soluble, chain-breaking antioxidants that prevents the propagation of free radical reactions. It is known that the coadministration of vitamins C and E is useful for reducing the oxidative stress of lead exposure and improves the prooxidant/ antioxidant balance of cells. Thiol-containing Conclusion and Summary 107 compounds bind lead at their –SH (thio) groups. Therefore the combination of thiol-containing compounds (e.g. DMSA) with antioxidants (e.g. vitamins C and E) may be useful as a compound of an effective treatment for lead toxicity. This study also, aimed to investigate the importance of DMSA as a chelating agent of lead, vitamins C and E, as antioxidants, in the treatment of the toxic effects of lead on histological sections of liver, kidney, spleen, stomach, intestine and testis of albino rats. Thirty male albino rats (Rattus rattus) approximately 8- 10 weeks old, their weight ranging from 160-180 gm. are used in the present study. They were divided randomly into five groups (6 rats each). The first group served as control. The second group received 100 ppm of lead acetate in drinking water daily for six weeks. The third group received lead acetate (100 ppm) daily in drinking water and 50 mg/Kg/body wt. DMSA two times per week for six weeks. The fourth group received lead acetate daily (100 ppm) in drinking water, 50 mg/Kg/body wt. vitamin E and 160 mg/Kg/body wt. vitamin C two times per week for six weeks. Whereas, the fifth group received lead acetate (100 ppm) in drinking water daily; and 50 mg/Kg/body wt. DMSA, 50 mg/Kg/body wt. vitamin E and 160 mg/Kg/body wt. vitamin C two times per week for six weeks. At the end of the experiments, rats from each group were anesthetized, then sacrificed by decapitation. After the animal dissection, liver, kidney, spleen, stomach, intestine and testes were taken and prepared for histological examination. • The results indicated that lead induced severe histological changes in liver, kidney, spleen, stomach, intestine and testis sections from rats. Conclusion and Summary 108 • The histological examination of the liver, kidney, spleen, stomach, intestine and testes sections from the rats treated with lead acetate combined with DMSA showed mild histopathological changes as an indication of the chelating action of DMSA. • The administration of lead acetate combined with both vitamins C and E reduced to greater extent the toxic effects of lead acetate on the histological sections of the rat organs used in the present study. These results revealed that the combination of vitamins C and E as antioxidants may be a beneficial treatments for lead toxicity in soft organs. • Co-administration of rats with lead acetate, DMSA, vitamin C and vitamin E showed a marked improvement in the histological structure of the histological sections of the rat organs used in the present study. In comparison with those treated with either DMSA alone, or the combination of vitamin C and vitamin E. These results indicate that the combination of DMSA, as a chelating agent and vitamins C and E, as antioxidants, provided a better treatments for the removal the histopathological changes induced by lead toxicity in soft tissues used in the present study |