الفهرس 
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Abstract
Rodents are considered as one of the most important pests in Egyptian agriculture. Anticoagulants act by preventing the normal mechanism that controls blood-clotting in targeted rodents. The development of tolerance to anticoagulant poisons was recorded in several parts of the world. This was more pronounced with the first generation anticoagulants in different part of the world. Many authors found the response to coumatetralyl and difenacoum to be quite similar in extending the prothrombin time in homozygous tolerant (Welsh strain) male Norway rats, while warfarin and diphacinone gave little response.
Also, several studies pointed out that some rat populations have devolved tolerance to some of toxic anticoagulants such as warfarin, bromadiolone and difenacoum. So our thinking turned to using coumatetralyl to overcome tolerance of other anticoagulant rodenticide. Some authors discover the potency of coumatetralyl where authors found that bait with coumatetralyl had greater efficacy than bait with zinc phosphide, perhaps because of its slow mode of action and the longer period of time between the ingestion of a lethal dose and the onset of symptoms. So, some studies suggested using other or new compounds are capable to overcome the tolerant rodents which have been developed such as Brodifacoum, floucomafin ,difenacoum and coumatetralyl.
The protocol desien included the followings:
1) Survey of Rodents in the field aiming to determine the dominant wild rodent species at the four sites in Assiut Governorate which are Manfalut (1), Deirout (2), Abnoub (3) and Assiut city.
2) Determine the LD50 of coumatetralyl of theses dominant wild rodent species at these the four sites.
3) Plasma Prothrombin time (P.T.), Clotting time, Bleeding time, Plasma International Normal Ratio (INR), Fibrinogen Degradation Products (FDPs).
4) For the experimental part of the design: All species Gerbillus gerbillus, Arvicanthis niloticus and Rattus rattus were treated with ¼ LD50 of COM. to show some its toxicological effects on oxidative damage liver kidneys, erythrocytic lysate and plasma. as well as some histological alterations in liver kidneys.
The results showed the followings:
I- The three dominant species of rodents in these sites, Thus we found the roof rat, Rattus rattus its dominanted in Deirout and Abnoub site , the Nile rat , Arvicanthis niloticus dominanted in Assiut site and the Deserted rat, Gerbillus gerbillus dominanted in Manfalut site.
II- The present results showed that: Gerbillus gerbillus with 80 g bw and bait consumption (b.c.) of 8 g, the LD50 of COM was 42.84 mg/kg (535 µg COM/ g bw), Avicanthis n. with 170 g bw and b.c. of 16 g, the LD50 of COM was 35.28g/kg bw (207 µg COM/ g bw), while Rattus r. with 110 g bw and b.c. of 12g, the LD50 of COM was 39.34 mg/kg (371 µg COM/ g bw). This result may let us to arrange these species from high to low doses (descending grade) according to the required of LD50 of COM for each of the three species as follow: Gerbillus gerbillus (535 µg COM/ g bw) followed by Rattus r. (371 µg COM/ g bw) , followed by Arvicanthis niloticus. (207 µg COM/ g bw). Thereby, Arvicanthis niloticus may be more suceptibility to coumatetralyl among the dominant wild rats.
III- The data obtained in the current study reveals that the greatest LD50 of COM was in Gerbillus gerbillus in spite of smallest average bw, while the lesser LD50 of COM was in Arvicanthis niloticus in spite of its bigger average bw. Consequently, it could suggest that the LD50 of COM for the wild rats was species-dependent not body weight dependent.
IV- All species Gerbillus gerbillus, Arvicanthis niloticus and Rattus rattus were treated with ¼ LD50 of COM and led to the following results.
1- Hematological Studies:
There were significant increases in International Normalized Ratio INR, Plasma Prothrombin time PT, clotting time and bleeding time with showing haemorage around liver in all tested species of rodents: Gerbillus gerbillus, Arvicanthis niloticus and Rattus rattus in response to ¼ LD50 of COM supplementation. In turn, there was no significant change in Fibrinogen Degradation Products (FDPs) for all these species.
There were no significant changes in the Ht, Hb, RBCs count and blood cell indices in response to ¼ LD50 COM treatments.
The normal values of the most hematological measured parameters in spite of the presence of visceral hemorrhage. This may be due to COM of ¼ LD50 of COM causes vascular permeability and escaping of some component of blood plasma perhaps led to elevating blood viscosity.
Supplementation of ¼ LD50 of COM led to significant rise in PLT count found in Gerbillus gerbillus, while it showed significant DROP in PLT count in both Arvicanthis niloticus and Rattus rattus in response to coumatetralyl.
This study suggests that the significant DROP in PLT count in both Arvicanthis niloticus and Rattus rattus in response to coumatetralyl may be associated with liver damage.
2- Biochemical study:
There were significant increases in free Hb in all species Gerbillus gerbillus, Arvicanthis niloticus and Rattus rattus treated with ¼ LD50 of COM. This finding suggests that free Hb may exacerbate the damaging effect of LD50 of COM on the kidney as well as vascular endothelium.
The rise in free Hb may exacerbate the damaging effect of LD50 of COM on the kidney as well as vascular endothelium.
There were significant rise in LPO level in liver of both Gerbillus gerbillus, and Arvicanthis niloticus and in bl. Plasma and in erythrocytic lysate of Gerbillus gerbillus in response to ¼ LD50 supplementation.
There were significant elevation of CAR.Pr in erythrocytic hemolysate of all studied rat species, while led to significant rise in renal CAR.Pr ot in both Gerbillus gerbillus, and Arvicanthis niloticus, while pronounced rise hepatic CAR.Pr of Gerbillus gerbillus, in response to ¼ LD50 COM.
There were significant depletion of CAT activity in erythrocytic lysate in Gerbillus gerbillus, and Arvicanthis niloticus, in both liver and kidney in Rattus rattus in response to ¼ LD50 COM comparing to control. This depletion in CAT activity may associated with disturbances in the activity of G6PD found in all tissue cells.
Supplementation of ¼ LD50 of COM significantly decreased SOD activity in liver of all studded rat species Gerbillus gerbillus, Arvicanthis niloticus and Rattus rattus, while in kidney, the SOD depletion did not appear except of rattus rattus.
In the present study, ¼ LD50 of COM significantly decreased GSH level in erythrocytic lysate in Gerbillus gerbillus, and Arvicanthis niloticus probably due to the depletion of NADPH required to regenerate GSH from oxidized to reduce form during counteracting the overproduction of ROS in response to COM treatment.
Supplementation of ¼ LD50 of COM did not affect the plasma CP level in both species: Gerbillus gerbillus, and Arvicanthis niloticus, while it significantly decreased plasma CP in Rattus rattus.
There was significant hypoglycemia accompanied with significant increase in both HSI and RSI in Gerbillus gerbillus suggesting shortage of glucose tissue disruption of the cellular energy transfer.
Treatment with ¼ LD50 COM administration induced significant DROP in NO levels in both kidney and liver in Arvicanthis niloticus and Rattus rattus. The rise of bl. free hemoglobin leads to a greater extent of inactivated NO, thereby probably causing vasoconstriction.
Supplementation of ¼ LD50 of COM rodenticide led to significant rise in eG6PD activity in Gerbillus gerbillus, and Rattus rattus, while it significant decrease Arvicanthis niloticus in its activity.
The increased G6PD activity may be attributed to increased production of NADPH required for regeneration of some antioxidants to counteract detoxification process as well as overproduction of free radicals.
Treatment with ¼ LD50 COM administration induced significant rise in plasma level of urea in all studied rodents and significant rise in plasma level of both creatinine and uric acid in both Arvicanthis niloticus and Rattus rattus. This result may be associated with kidney damage.
Treatment with ¼ LD50 of COM led to pronounced decrease in liver glycogen accompanied with renal glycogen deposition in only Gerbillus gerbillus. This may affect the kidney function in this species.
Treatment with ¼ LD50 of COM led to marked decrease in plasma TFAA in both Arvicanthis niloticus and Rattus rattus. This result may be related to the COM-induced hemorrhages around liver and general viscera as well as probability of increased vascular permeability concomitant with escaping the main plasma contents.
It is found that, both activities of serum aspartic aminotransferase AST and alanine aminotransferase ALT were significantly elevated in the three studied species Gerbillus gerbillus, Arvicanthis niloticus and Rattus rattus in response to supplementation of ¼ LD50 of COM.
3-- Histopathological studies:
Histopathological examination of HE-stained kidney sections revealed that the treatment of rats with coumatetralyle of Gerbillus gerbillus, Arvicanthis niloticus and Rattus rattus showing vascular changes were in the form of interstitial edema, congestion of the blood vessel and swelling of the glomeruli as a result of congestion and Periglomerular mononuclear cell infiltrations in the form of lymphocytes were also seen, dilatation of Bowman’s spaces, as well as proliferation of mesangial cells.
Examination of the kidney of the three dominant rat species revealed normal histological architecture in control group.
Histopathological examination of HE-stained liver sections revealed that the treatment of the three dominant rat species with coumatetralyle showing variable changes were in the form of vascular and cellular changes. The vascular changes were in the form of congestion of the central vein. The hepatocellular changes were in the form of multiple focal areas of necrosis infiltrated with mononuclear cells, severe dilation of veins, and vacuolar degeneration of the hepatocytes.
Examination of the liver of the three dominant rat species of control group showing normal histological architecture.
Conclusion
In conclusion, This stydy found that the roof rat, Rattus rattus its dominanted in Deirout and Abnoub site , the Nile rat , Arvicanthis niloticus dominanted in Assiut site and the Deserted rat, Gerbillus gerbillus dominanted in Manfalut site. The present result shows: Gerbillus gerbillus with 80 g bw and bait consumption (b.c.) of 8 g, the LD50 of COM was 42.86 mg/kg (535 µg COM/ g bw), Avicanthis n. with 170 g bw and b.c. of 16 g, the LD50 of COM was 35.29 g/kg bw (207 µg COM/ g bw), while Rattus r. with 110 g bw and b.c. of 12g, the LD50 of COM was 39.34 mg/kg (371 µg COM/ g bw).
The supplementation of ¼ LD50 of COM significantly elevates oxidative stress parameters, decreasing antioxidants in erythrocytic lysate, kidney and liver tissues, affect kidney and liver function in addition it exerts deleterious effect on histological structure of liver and kidney in the three dominant species of rodents with different extents. The present results suggested that the effects of ¼ LD50 of COM on the three dominant species were very toxic as well as it has a potent ability to reduce these rodents by lower cost and probably less pollution.