Structural and biochemical changes in mitochondria after cisplatin treatment of Dalton's lymphoma-bearing mice.
Cisplatin treatment of tumor-bearing mice and analysis of ultrastructural features of mitochondria in the kidney and Dalton's lymphoma cells showed the appearance of more roundish mitochondria with thickened membranes. It also caused the reduction in the number and irregularity in the shape of cristae and formation of vacuoles in the mitochondria. After cisplatin treatment, decreased level of protein, succinate dehydrogenase activity, and increased level of lipid peroxidation were noted in Dalton's lymphoma tumor cells and kidney. Cisplatin-mediated decrease in SDH activity, GSH level and an increase in LPO in the mitochondria of kidney could play an important role to produce nephrotoxicity. However, in DL cells, decrease in cellular GSH could be noteworthy than mt-GSH, along with decrease in SDH activity and increase in LPO in the cisplatin-mediated anticancer activity. These changes could play an important role to produce both the cisplatin-mediated effects i.e. anticancer activity and nephrotoxicity. Cisplatin-induced biochemical and ultrastructural changes in mitochondria after cisplatin treatment should be an important factor in the development of biochemical injury in mitochondria and affecting the overall metabolism in the cells. The findings from the present studies indicate multilevel effect of cisplatin in the cells and do support the earlier view that mitochondria could be a critical target in cisplatin-mediated anticancer activity and toxicity in the hosts.
Prasad
Surya Bali
SB
Cell and Tumor Biology Lab., Department of Zoology, North Eastern Hill University, Shillong 793022, India. sbpnehu@hotmail.com
Rosangkima
Gabriel
G
Kharbangar
Arpaia
A
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use* / Q000633:toxicity; D002945:Cisplatin / Q000494:pharmacology / Q000627:therapeutic use* / Q000633:toxicity; D007668:Kidney / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D015227:Lipid Peroxidation / Q000187:drug effects; D008223:Lymphoma / Q000188:drug therapy* / Q000648:ultrastructure; D051379:Mice; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure; D011506:Proteins / Q000187:drug effects / Q000378:metabolism; D013385:Succinate Dehydrogenase / Q000378:metabolism
D000970:Antineoplastic Agents; D011506:Proteins; D013385:Succinate Dehydrogenase; D002945:Cisplatin