Ultrastructural changes of aminoglycosides on rats

Gentamicin, one of the aminoglycoside antibiotics, was administered intraperitoneally twice a day at a dose of 4 mg/kg body weight, a dose relevant to those used in the clinical practice. The kidney and liver were examined by light [semithin sections] and electron microscopy after 2, 7 and 14 days of treatment. Biochemical changes were also studied after the same periods and were found to be statistically insignificant even after 14 days. However, morphology of the liver and kidney, examined by light microscopy, was unchanged throughout the whole period of the study as compared with controls. The renal ultrastructural changes detected were dependent on the duration of drug administration and confined primary to the proximal tubule. Specific lysosomal alterations were detected as early as 2 days of treatment, these consisted of increased number of cytosegresomes, many of which contatined electron -dense multilamellar structures myeloid bodies. Alterations of the other subcellular structures were observed only after 7 and 14 days of treatment. the golgi apparatus became hypertrophied and the number of ribosomes were increased. Later, the mitochondria were affected giving the picture of megamitochondria. In addition, distal tubular cells showed marked vacuolization and disruption of the basal cell architecture. The most striktrig hepatic changes were prominent proliferation of perixosomes. prominent increase in smooth endoplasmic reticulum and a disruption of the rough endoplasmic reticulum. Thus these early ultrastructural alterations may indicate that therapeutic doses of gentamicin can induce renal and hepatic dysfunction in humans. This may be an important fact on limiting the clinical utility of gentamicin

Effects of prenatal acetaminophen in the outcomes of pregnancy on rats

Acetaminopen, a popular nonprescription analgesic-antipyretic drug, was administered orally to pregnat rats at a dose levels of 0 [control] .25, 50, 100 200 and 400 mg/kg boy weight / day on days I to 15 of gestation, The dams were sacrificed on the day 21 of pregnancy, and the fetuses; were removed by caesarian section and examined. Body weight showed evidence of maternal toxicity as exhibited by marked increase in liver weight and decreased body weight gain. No increase in the incidence of resorptions was observed even at 400 mg/kg body weight, a dose several fold higher than those used in human clinical practice [10-20 mg/kg body weight]. There was a dose-related decrease in fetal body weights which was statistically significant at 200/mg/kg weight or more, Examination of the fetuses revealed insignificant increase in the incidence of gross, skeletal and internal malformations at any dose in comparison with the controls. However, one of the fetuses in the group which recevied 400 mg/kg weight showed short tail and club foot. Thus, no evidence of embryocidal and teratogenic effects was boserved with this analgesic antipyretic drug at the recommended therapeutic dose in rats. Acetaminophen should be considered the safest analgesic-antipyretic drug during pregnancy