Chloramphenicol and Ampicillin-Induced Changes in Rat Hepatic Esterase and Amidase Activities

Abstract

The influence of ampicillin and chloramphenicol administered intraperitoneally singly or in combination on the protein content and the activities of hepatic esterase and amidase have been investigated in rats. The results have been compared to the effects of phenobarbitone (inducer) and p-nitrophenyl-phosphate (inhibitor) of hepatic hydrolases. Ampicillin pretreatment reduced protein level and amidase activity by 3.5% each but caused a significant increase (8.1%) in total esterase activity compared to controls. Chloramphenicol treatment caused an overall decrease in protein level, esterase and amidase activities respectively by 11%, 11%, and 35% over controls. Combined administration of both drugs resulted in a decrease in protein, esterase and amidase activities by 11.5%, 12.5%, and 41.2% respectively, thus mimicking the effects obtained with chloramphenicol alone. The changes induced by administration of the drugs particularly in combination on the constituent enzymes of rat hepatic hydrolases may affect the ability of the body to deal with exposure to environmental chemicals if extrapolated to man.

Influence of Chloramphenicol on Rat Hepatic Microsomal Components and Biomarkers of Oxidative Stress: Protective Role of Antioxidants

“…The drug produced a dose‐dependent decrease in the body weight, relative liver weight and protein content compared to control (P<0.05). These results are in accordance with earlier investigations ( Wakabayashi et al 1997 ; Farombi et al 2000a & b ).…”

“…Relating this to our present observation, chloramphenicol's increase in cholesterol/phospholipid ratio as well as lipid peroxidation indicate a decrease in membrane fluidity, which may result in alteration in membrane function including changes in membrane receptor, enzyme accessibility and activation of the enzymes (Wiseman 1995). The results confirm earlier investigations on the influence of antimalarial drugs (Farombi & Emerole 1998; Farombi et al 2000a & b) and CCl 4 (Farombi 2000) on the lipid parameters.…”

“…Determination of malondialdehyde and lipid hydroperoxide formation. Thiobarbituric acid reacting substances (TBARS) formation was measured as described previously (Farombi et al 2000a & b). Briefly, 1 mg/ml of the microsomal fraction in isotonic phosphate buffer, pH 7.4 was incubated for 6 hr at 37 ° in a shaking water bath.…”

“…Studies have indicated that chloramphenicol can inhibit oxidase activity of cytochrome P450 (CYP) and inhibit metabolism and elimination of drugs such as xylazine (Halpert et al 1985; Grubb et al 1997). Chloramphenicol is also known to affect other hepatic enzymes as demonstrated by our recent studies on its effects on hepatic esterase and amidase activities as well as antioxidant enzymes (Farombi et al 2000a & b; Farombi 2001).…”

Role of Oxidative Stress in Reproductive Toxicity Induced by Co‐administration of Chloramphenicol and Multivitamin–Haematinics Complex in Rats

“…CAP enabled the oxidative stress response of neutrophils and increased ROS production [13]. It has also been shown to inhibit drug metabolizing enzymes, affect antioxidant enzymes and hepatic esterases and amidases [4,14].…”