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Abstract
Methionine is the most toxic amino acids when taken in excessive amounts. The present study was designed to investigate the toxicological effects of methionine on the growth performance, hematological parameters, serum biochemical studies, oxidative cascade and histopathololgical changes. Eighty male &female Swiss mice were used in present study. These mice were divided into four groups (20 mice in each male &female) as follow: First group: fed on balanced ration and considered as control group. Second group: was administered 1% methionine mixed with balanced ration. Third group: was administered 3% methionine mixed with balanced ration. Fourth group: was administered 6% methionine mixed with balanced ration. The methionine added to diet which fed ad libitum till 8th weeks The experiment was continued for 8th weeks, during which mice in all groups were observed daily and clinical signs were recorded. Body weight was evaluated weekly. Collection of blood samples were performed at 4th and 8th weeks. Blood samples were divided into: blood for hematological studies collected on disodium EDTA 10% solution and serum for biochemical analysis. Tissue specimens from the liver collected at 4th and 8th weeks for determination of oxidative cascade. Histopathological studies were done on liver, spleen, kidney and heart at 4th and 8th weeks. Hematological examination included red blood cells count, packed cell volume, hemoglobin concentration , red blood cells indices [(MCV) and (MCHC)], total and differential leucocytic count.While serum biochemical parameters included liver function tests (ALT and AST), blood glucose level and kidney function tests (urea and creatinine).Tissue specimens were collected from liver for determination of malondialdehyde (MDA), antioxidant status [reduced glutathione (GSH) and glutathione -s-transferase (GST)]. Specimens from liver, spleen, kidney and heart were collected for histopathological examination. The results obtained in this study could be summarized as follows: The mice treated with methionine suffered from lowered activity and depression. While no clinical signs were shown in control group throughout the experimental period. Post mortum changes revealed splenomegaly, hepatomegaly that was observed in treated groups at 8th weeks of the experiment. The initial body weight of mice in different groups showed no statistical differences, while final body weight and weight gain of mice in treated groups showed significant decrease compared to control group. The significant decrease in RBCs, Hb and haematocrit volume and significant increase in MCV revealed hemolytic anemia that induced in treated groups at 4th and 8th weeks of the experiment. The leucogram revealed significant leucocytosis with significant lymphocytosis and esinophilia in treated groups at 4th and 8th weeks of the experiment. There was significant decrease in neutrophiles in treated groups at 8th weeks of the experiment. The liver enzymes (ALT and AST) showed significant increase in treated groups compared to control group throughout the experimental period. The blood glucose level revealed significant decrease in treated groups compared to control group throughout the experimental period. The antioxidant status including GSH and GST revealed significant decrease in treated groups while MDA showed significant increase in these groups compared to control group. While in female mice no significane changes in all previous results because female hepatocytes were less sensitive to 3- methylthiopropionic acid toxicity than males, which may partially explain their resistance to methionine toxicity, also methionine hepatotoxicity in male and female mice differ may be due to sensitivity differences to methionine hepatotoxicity. 17 β- estradiol hormone in female mice lower level of methionine uptake in female hepatocytes compared to male could contribute to their resistance to methionine hepatotoxicity . The histopathological examination of liver of male mice in all groups revealed diffuse hepatic degenerative changes in the form of vascular, hydropic and fatty degeneration at early stage of examination. These changes were more sever in mice with high dose methionine. At end of experiments inflammatory cellular infiltration, diffuse fatty degeneration, hepatic cell disarrangement with bile hyperplasia were seen. The examined spleen of mice showed lymphoid depletion which increased in its severity with time. In addition splenic hemosiderosis was recorded. focal areas of hemorrhages and extramedullary hematopoiesis characterized by infiltration of large hematopoietic precursor cells in the red pulp in the spleen. Renal tubular nephrosis was seen in examined kidneys of mice. These changes were sever at the end of experiment particulary in mice given high dose of methionine. and heart showed congestion of the myocardial blood vessels and intermuscular capillaries. Focal areas of hemorrhages accompanied with hyalinization of some muscle fibers and intermuscular lymphocytic cellular infiltration were also observed