Cisplatin and doxorubicin are active chemotherapeutic agents used in the treatment of a wide variety of tumors. But these drugs have undesirable toxic effects on the liver cells. Silymarin is known to have hepatoprotective effects as it is capable of stabilizing the liver cell membrane.
The aim of this work: was to study the possible protective effects of silymarin on the induced hepatotoxicity in adult albino rats and also the structure of the liver after withdrawal of these drugs.
Materials and Methods:
Seventy adult male rats were divided into seven equal groups. In the control group, the rats were injected intraperitoneally with 2ml of normal saline/kg on an alternate days for 20days. In the cisplatin group, the rats were injected intraperitoneally with cisplatin at a dose of 1mg/kg on an alternate days for 20 days. In cisplatin plus silymarin group, the rats were injected intraperitoneally with cisplatin at a dose of 1mg/kg plus silymarin in a dose of 16mg/kg/day orally by gastric tube for 20 days. In cisplatin withdrawal group, the rats received cisplatin in the same dose followed by withdrawal of cisplatin for 4 weeks. In the doxorubicin group, the rats were injected intraperitoneally with doxorubicin at a dose of 1mg/kg on an alternate days for 20 days. In doxorubicin plus silymarin group, the rats were injected intraperitoneally with doxorubicin at a dose of 1mg/kg plus silymarin in a dose of 16mg/kg/day orally by gastric tube for 20 days. In doxorubicin withdrawal group, the rats received doxorubicin in the same dose followed by withdrawal of doxorubicin for 4 weeks. At the end of experiment, all rats were sacrificed using ether inhalation. The liver specimens were prepared for light, electron microscopic analysis and biochemical changes.
Results:
Cisplatin produced loss of normal hepatic architecture with marked vacuolations. There was marked cellular infilteration around the dilated and congested portal vein. Electron microscopic examination showed that cisplatin produced decrease in number of organelles and the mitochondria are arranged in clumps around the nuclei. There was nuclear changes in the form of pyknotic nuclei with irregular outlines. Administration of silymarin with cisplatin produce marked improvement as most of hepatocytes regained to normal structure. Also with cisplatin withdrawal, there was partial reduction of cisplatin toxic effects with slight return to the picture of control group. Doxorubicin also similar to cisplatin, it produced marked hepatotoxicity with marked cytoplasmic vacuolations and loss of hepatic architecture, also administration of silymarin with doxorubicin produced partial improvement, wherease no evidence of improvement after long term doxorubicin withdrawal as most of the hepatocytes had varying degree of degeneration.
Conclusion:
¬ The toxic effects of cisplatin on the liver of adult rats was markedly minimized by concomitant administration of silymarin and cisplatin with partial improvement after cisplatin withdrawal. However, administration of doxorubicin with silymarin showed moderate improvement with no evidence of recovery after long term doxorubicin withdrawal. This means that doxorubicin is of more toxic effects than cisplatin.
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