cefotaxime and Weight-Gain

Wistar male rats were treated for six days with broad spectrum beta-lactam antibiotics, latamoxef, and cefotaxime. On the seventh day, the number of fecal anaerobic microbes decreased, total fecal bile acids decreased, and bile acid pools increased. Secondary bile acids such as beta-hyocholic, hyodeoxycholic, lithocholic, and deoxycholic acids decreased in the feces while the primary bile acids, cholic, beta-muricholic, and chenodeoxycholic acids, became predominant. Coprostanol, a microbial metabolite of cholesterol, also disappeared from the feces during the treatment. The cecum enlarged to almost twice the size of that in control rats, whereas the liver weight was not significantly changed. After treatment was stopped, the number of fecal microbes returned to the initial counts within a week, but restoration of bile acid and cholesterol metabolism required at least three weeks.

Topics: Animals; Anti-Bacterial Agents; Bacteria, Anaerobic; Bile; Bile Acids and Salts; Cefotaxime; Chenodeoxycholic Acid; Cholic Acid; Cholic Acids; Diet; Feces; Intestines; Liver; Male; Moxalactam; Organ Size; Rats; Rats, Wistar; Weight Gain

Six-month chronic subcutaneous toxicity study of cefodizime sodium (THR-221) in rats was carried out with dose levels of 3000, 1000, 300 and 100 mg/kg/day. The systemic change observed was slightly decreased spontaneous activity, which appeared only in a very few animals. At the injection site of the animals at 1000 and 3000 mg/kg/day, various cutaneous changes (subcutaneous retention of fluid, incrustation, loss of hair and perforation) were observed. The body weight gains of the males at 1000 and 3000 mg/kg/day were depressed from 1 month of administration onward, but the food consumption was not affected in any group. The water intakes at 1000 and 3000 mg/kg/day were increased. Hematological findings were signs of anemia, a slight decrease in red blood cell count or increases in platelet and/or reticulocyte counts in all THR-221 groups. At 3000 mg/kg/day, increases in white blood cell and neutrophil counts and a decrease in lymphocyte count were also observed. Plasma chemistry revealed decreases in total protein amount and, albumin (A) or globulin (G) amounts, and a decrease or increase in A/G ratio in all compound groups. Autopsy revealed dilation of the cecum and hematoma, dark red spots and yellowish brown spots in the subcutaneous tissue at the injection site in all THR-221 groups. Hypertrophy of the spleen was also noted at 300-3000 mg/kg/day. Changes in organ weights were a decrease in liver weight in all compound groups and an increase in spleen weight at 3000 mg/kg/day. Microscopically, the following were observed: brown granules or hyaline droplets in the epithelium of renal tubules; hemorrhage and inflammatory changes in the subcutaneous tissue at the injection site; and an increased number of lymphocytes or granulocytes in the spleen and bone marrow. Urinalysis and ocular and auditory tests showed no changes related to THR-221. From the present results, the toxicologically non-effective doses of THR-221 are considered to be 300 mg/kg/day for male rats and more than 1000 mg/kg/day for female rats.

Topics: Anemia; Animals; Blood Cell Count; Bone Marrow; Cecum; Cefotaxime; Epithelium; Female; Hypertrophy; Injections, Subcutaneous; Kidney Tubules; Male; Rats; Rats, Inbred Strains; Serum Albumin; Serum Globulins; Skin; Spleen; Weight Gain