Cisplatin- and dietary ascorbic acid-mediated changes in the mitochondria of Dalton's lymphoma-bearing mice.
Cisplatin treatment caused a significant increase in the life span of ascites Dalton's lymphoma (DL) Tumor-bearing (TB) mice. However, as compared to cisplatin (CP) alone, combination treatment with ascorbic acid plus CP resulted in better therapeutic efficacy against murine DL. Cisplatin treatment of TB mice resulted in the appearance of thickened and irregular arrangement of mitochondrial cristae in the liver, kidney and DL tumor cells. Combination treatment of the hosts with ascorbic acid and CP lessened deformities in the mitochondria of liver and kidney, while in tumor cells, this increased the formation of vacuoles and disruption in mitochondrial cristae. Cisplatin treatment decreased the succinate dehydrogenase (SDH) activity in the mitochondria of kidney and DL cells and combination treatment caused further decrease in SDH activity in kidney and DL cells during 24-48 h of treatment. After CP treatment, the protein content in the mitochondria of these tissues decreased, and during combination treatment, it showed significant improvement. Mitochondrial lipid peroxidation (LPO) increased in these tissues after CP treatment. However, combination treatment significantly decreased mitochondrial LPO in liver and kidney but increased in DL cells. This increase in mitochondrial LPO in DL cells and decrease in liver and kidney could play an important role in the antitumor activity of combination treatment and at the same time reduce CP-induced toxicity in the host. However, further study may be desirable to explore some aspects of the mechanism(s) involved in these changes in mitochondria.
Cell & Tumor Biology Lab., Department of Zoology, North-Eastern Hill University, Shillong-973022, India.
Kham R M
KR
Martha
Gabriel
G
Rosangkima
Longchar
L
Amenla
Thengtom
T
Rongpi
Surya B
SB
Prasad
D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000494:pharmacology; D000975:Antioxidants / Q000008:administration & dosage / Q000494:pharmacology*; D001201:Ascites / Q000473:pathology; D001205:Ascorbic Acid / Q000008:administration & dosage / Q000494:pharmacology*; D002945:Cisplatin / Q000008:administration & dosage / Q000494:pharmacology*; D004359:Drug Therapy, Combination; D007668:Kidney / Q000187:drug effects / Q000378:metabolism; D015227:Lipid Peroxidation / Q000187:drug effects; D008223:Lymphoma / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D051379:Mice; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D008930:Mitochondria, Liver / Q000187:drug effects / Q000378:metabolism; D009374:Neoplasms, Experimental / Q000188:drug therapy / Q000473:pathology; D013997:Time Factors
D000970:Antineoplastic Agents; D000975:Antioxidants; D001205:Ascorbic Acid; D002945:Cisplatin