The histological effects of different doses of methidathion pesticide on the lungs of Mus musculus mice

: The current study investigated the effect of two doses of the organo-phosphorous pesticide methidathion on the lungs of laboratory mice Mus musculus L. The animals were divided into three equal groups: the first group represented the control group injected through the intraperitonial membrane with 0.1 ml of normal saline, and the second and third groups were injected with 0.1 ml of methcathinone solution at a concentration of (1.2, 2.4 mg/kg) respectively. The histological study of the lung of groups treated with methadone showed the presence of histological changes in the low-dose group represented by hyperplasia represented by the enlargement and swelling of the lining of the alveoli and the narrowing of its cavities as well as congestion, bleeding and infiltration of inflammatory cells. Whereas the second treated group showed more histological changes in lung composition, represented by the infiltration of inflammatory cells near the respiratory channels and around the walls of blood vessels that appeared congested with blood, edema and bleeding between the alveoli were noted.


Introduction
Environmental pollution is one of man's difficulties in the modern era, and it began with the recovery of industry and man's entry into the era of industry and mining, as well as increased awareness of significant energy resources like coal and petroleum, including the emissions and garbage produced as a result. Various industrial substances, such as detergents, insecticides of various sorts, agricultural fertilizers, and industrial plastics, were gradually introduced into the environment until they exceeded the critical limit, causing the ecosystem to be disrupted and its carrying capacity to deteriorate 1 . Organophosphorous pesticides are chemicals originally produced from the reaction of alcohol and phosphoric acid, and these compounds contain a central phosphorous atom with a sulfur or oxygen double bond 2 . They are esters of phosphoric acid and its derivatives, and the general chemical structure of these compounds consists of phosphoric. acid (p = o) or thiophosphoric (p=s) 3 . Methidathion is a non-systemic pesticide that has a contagious or contact effect, as it enters the body through inhalation, stomach, skin, or contact with eyes and damaged skin, facilitating its rapid absorption. This compound is used to eliminate different types of insects and mites in several crops such as fruits, vegetables, tobacco, alfalfa, sunflower, home gardens, etc. It works by inhibiting a specific enzyme in the target insects. 8,9,10 . The toxicological action of methadone is complex and involves many major and minor metabolic pathways, and a wide range of compounds have been identified. (DPR, 2007). Figure (2) shows the methadathion metabolic pathway, where the process of methadione decomposition takes place rapidly, and the main route of methadathione metabolism in plants and animals is through hydrolysis, oxidation and methylation 11,12,13 Different doses were studied to evaluate the effects of methidathion on hematology parameters, such as hemoglobin and red cells ount in laboratory animals. 14,15 . 16 studied the effect of the organophosphorus pesticide fenitrothion on Spragu-Dawley rats at an oral dose of 20 mg/kg for 28 days and between morphological and biochemical disturbances in liver tissue. As a result of the widespread use of agricultural pesticides in general and insecticides in particular, and their health consequences, the current study aimed to know the effect of the phosphorous insecticide Methidathion on lung tissue.

Materials and Methods
White laboratory mice, L. Mus musculus, strain BALB /C, which were brought from (Drug Control Center / Baghdad and the Iraqi Center for Cancer Research) and bred in the animal house of the Department of Life Sciences / College of Education / University of Basra, under controlled conditions were used. Regarding temperature 20-25 ° C, the illumination cycle is 12 hours of light and 12 hours of darkness throughout the study period 17 . The mice were placed in plastic cages of standard sizes (30 x 12 x 11) cm manufactured by North Kent plastic Kent U.K. The cages were spread with sawdust, as it was changed weekly, and they were fed using the broth. Laboratory mice (female and male) aged 10-12 weeks and weighing 20-25 g were divided in each of the tests of the current study into three groups, each consisting of 8 mice, as follows: control, treated A and treated B groups. 1. Control group: Injected intraperitonealy with 0.1 ml of normal saline. 2. Treated group A was injected intraperitoneally with (0.1 ml) of the pesticide Methidathion at a concentration of (1.2 mg/kg). 3. Treated group B was injected intraperitoneal with (0.1 ml) of methadathione at a concentration of 2.4 (mg/kg). Laboratory mice were given 15 injections, one injection per day, for 15 days. The animals were sacrificed, and organs, including the lungs, were taken for fixation and histology processing.

Results (i) Control group:
The results of the microscopic examination showed that the lungs of the control group mice consist mainly of alveoli, which are characterized by multifaceted pockets with thin walls open on one side in the alveolar sac, and the alveoli are separated from each other by the interalveolar septum. The alveoli are lined with two types of epithelial cells, Type I and Type II (Type I), which are squamous epithelial cells; their nuclei are clear, and their cytoplasm is thin. Type II are large cells whose nucleus is compact and whose cytoplasm is abrupt. They are found singly or in small groups, especially in the places of the union of the interalveolar barriers (Fig. 1).
(ii) Low dose group A: Microscopic examination showed the presence of histological changes represented by the enlargement of the lining of the alveoli (Fig.2 ), swelling (Fig.3 ), hyperplasia of the alveolar lining and the narrowing of its cavities (Fig.4,5,6 ), as well as the occurrence of bleeding and infiltration of inflammatory cells.

(iii) High dose group B:
The histological changes, represented by the infiltration of inflammatory cells near the respiratory channels and around the walls of blood vessels that appeared congested with blood (Figures7,8 ), edema and bleeding between the alveoli were noted (Figures 9 and 10). Histological examination showed hyperplasia in the two types of cells lining the alveoli (Figure 11), and these cells in other areas of the lung suffered from degeneration and swelling (Figures 12,13,14,15and 16).

Discussion
Malathion enters the body through the skin, lungs, and digestive tract. Skin absorption, on the other hand, is relatively modest. Most organophosphates must be activated by microsomal enzymes in the liver and other organs, including the brain, via oxidation of the P=S bond to the more deadly P=O complex. Malathion esters, on the other hand, rapidly destroy the carboxy-ethyl ester groups in malathion. Malathion is effectively detoxified due to this action, accounting for its low toxicity to animals compared to several other organophosphates. The liver and kidneys are primary distribution sites, indicating that malathion is rapidly detoxified and eliminated 18 . Organophosphate pesticides are efficiently absorbed through inhalation, ingestion, and skin penetration, and this exposure across several pathways can have serious 19 . It can harm the lungs and induce respiratory failure (Gayton, 1976), according to which sub-lethal dosages of the insecticide diazinon cause dose-related histopathological lesions in the guinea pig lung .Monocyte infiltration, hemorrhage, vascular congestion, edema, thrombosis, and necrosis were the most common abnormalities. Following that, the lung tissue changes observed in the current study, which involved using the insecticide Diazinon Result, were similar to and concordant with those reported by several authors in different experimental animals exposed to organophosphorous insecticides 21,22 . The lower antioxidant status in the animal body due to chemically induced pulmonary vascular congestion and venous congestion resulting in higher blood pressure in the veins and capillaries can be ascribed to these histological alterations. This may put undue strain on nearby structures 24, 25 . 26 was similar to the current study in that the pesticide has potential health risks and effects on lung and liver tissue due to exposure to inhalation. A total of 16 mature Swiss mice, including a control group, were used in the investigation. Animals were placed into four groups, each with four mice. They were exposed to a 0.5 percent dilution of the pesticide in an inhalation chamber (40 35 25 cm3) for various durations, whereas control animals were not. Exposure to the pesticide causes time-related changes in the liver and lungs, according to histopathological abnormalities in the lungs and liver tissues. It disrupts the normal regulation of liver tissue, resulting in liver injury, necrosis, a considerable reduction in cell number, sinus widening, and fibrosis. When inhaled, pesticides cause edema, cell clumping, and necrosis in the lungs. Pulmonary edema, alveolitis, and pulmonary fibrosis are also symptoms. When these findings are considered together, it is clear that pesticides can have substantial consequences for non-target creatures when inhaled.

Conclusions
The low and high of pesticides caused toxicity and histopathology in the Lung tissue of male and female laboratory mice Acknowledgements. I would like to thank my work friends