Abstract: Objectives: To determine structural and ultrastructural changes in adult rat liver induced by cisplatin (Cis)
and to evaluate the impact of drug withdrawal and the effect of silymarin on cisplatin heptotoxicity. Material &
Methods: Forty male albino rats were divided into 4 equal groups: Control group kept on normal diet without
medications, Positive control (Cis-1) group received cisplatin every other day for 10 injections, Withdrawal (Cis-2)
group received cisplatin every other day for 10 injections followed by drug withdrawal for 4 weeks from the last
injection and Study (Cis-3) group received cisplatin every other day for 10 injections plus a daily oral dose of
silymarin. Cisplatin was injected intraperitoneally in a dose of 1mg/kg but silymarin was given orally in a dose of 16
mg/kg dissolved in 2 ml distilled water and given orally by gastric tube. Both control and study groups were
sacrificed, liver specimen were obtained and prepared for light (L/M) and electron (E/M) microscopic examination.
Results: L/M examination of Cis-1 specimens showed loss of normal hepatic architecture with diffuse cytoplasmic
vacuolations of most hepatocytes, some hepatic nuclei are vacuolated and eccentric with areas of focal necrosis of
hepatocytes, focal hemorrhage and small areas of degeneration among hepatocyte. Connective tissue is increased
around the dilated central vein (CV) and portal tract (PT). PAS staining showed vacuolated hepatocytes with
absence of glycogen granules. Cis-2 specimens showed restored hepatic cords with congested CV, connective tissue
is increased around CV and extended to nearby blood sinusoids. Most hepatocytes have good positive PAS for
glycogen granules. In Cis-3 specimens, few hepatocytes were vacuolated, PT appeared normal and hepatocyte
cytoplasm showed good positive PAS reaction for glycogen granules. E/M examination of Cis-1 specimens showed
marked intranuclear and intracytoplasmic vacuolations, decreased number of organelles and the nuclei of some
hepatocytes are shrinked with irregular outlines. In Cis-2, hepatocytes’ architecture was normal with rounded nuclei
and cytoplasm contains numerous intact mitochondria. Most hepatocytes contain few vacuoles; however some
hepatocytes show many vacuoles. Cis-3 group showed normal hepatocytes with rounded nucleus and nucleolus,
cytoplasm contains numerous organelles and numerous intact mitochondria. Conclusion: Oral administration of
silymarin ameliorated the deleterious hepatic structural and ultrastructural toxic effects of cisplatin. Cytotoxic drug
withdrawal allowed partial restoration of hepatic architecture so silymarin administration was recommended till
complete hepatic convalescence to augment the effect of drug withdrawal. |
