ABSTRACT
There are many concerns about safety of food contaminated with antibacterial residues of veterinary drugs in meat, milk and their products. Ghloramphenicol is a potent and broad spectrum antibiotic used in veterinary practice and it is used extensively in nonindustrialized countries, thus the need to design this experiment to explore the dose and time response effects of chloramphenicol administration on several parameters in either prophylactic or therapeutic dose for 12 weeks on liver enzymatic activities as well as histopathological changes. A total number of 240 male albino rats were divided into four equal groups. Solutions of chloramphenicol succinate were diluted in distilled water and administered to rats by gavages at a constant dose volume of 10 ml/kg body weight. Chloramphenicol was administered to the first and second groups in a dose of 25 and 50 mg/kg body weight daily for 12 weeks. Rats in the third group [considered as a control group of the group one] and fourth group [considered as a control group of the group two] were given distilled water in a volume of 10 ml/kg body weight l0 rats from each group were scarified under anesthesia after 2,4,6,8,10 and 12 weeks post dosing. Samples of blood were obtained without anticoagulant for determination of serum AST, AP, Gamma-GT and LDH. Liver samples were taken for histopathological examination. Results of liver enzymatic activities including serum AP and, GT revealed a significant increase in both prophylactic and therapeutic doses of chloramphenicol treated-rats compared with control. Histopathological study revealed degenerative changes of hepatic parenchymal cells corroborated to serum enzymatic activity. Serum LDH concentrations showed a significant increase after 2nd week of exposure until the end of experiment at 12th week. Changes in the serum levels of AST were not statistically significant in both prophylactic and therapeutic dose administered groups. Hepatotoxic effect of chloramphenicol is attributed to inhibition of hepatic cytochrome P45o. High rate of tissue turnover with destroyed cells leading to an elevated serum LDH. Therefore, increase the level of this enzyme in this study may be attributed to cytotoxic effect induced by chloramphenicol on multiple cellular compartments including hepatic tissue breakdown. These lesions varied greatly in its severity and distribution according to the duration of exposure as well as the dose of chloramphenicol. Hydropic degeneration with hypertrophy of the Kupffer cells associated with the loss of ribosomes in rough endoplasmic reticulum was recorded. Mitochondria appeared slightly swollen, the bile canaliculi dilated and some areas of necrosis was the most common histopathological change. Swelling in hepatic cells recorded in this study besides congestion of the hepatic vasculature, accumulation of fat globules and presence of bundles of collagen fibers in between the hepatic cells and in the Disse space represented chronic reaction to chloramphenicol toxicity or side effects. Such reaction could be considered as secondary for hepatocellular degeneration and necrosis