Document Detail

Doxorubicin affects testicular lipids with long-chain (C18-C22) and very long-chain (C24-C32) polyunsaturated fatty acids.
MedLine Citation:
PMID:  17638909     Owner:  NLM     Status:  MEDLINE    
Doxorubicin disrupts spermatogenesis by causing apoptosis of spermatogonia and primary spermatocytes. The aim of this study was to examine the effect of this agent on adult rat testicular lipids and their fatty acids. A single dose (7.5 mg/kg) and a multidose regime (3 mg/kg once a week for 4 weeks) were evaluated. Both treatments resulted in the gradual loss of spermatogenic cells and determined a marked reduction in testicular size and weight 9 weeks after their start. Germ cell loss was accompanied by a decrease in phospholipids, including glycerophospholipids and sphingomyelin. Concomitantly, glycerophospholipids lost selectively their major polyunsaturated fatty acid (PUFA), 22:5n-6, and sphingomyelin lost its major very long-chain PUFA (VLCPUFA), 28:4n-6 and 30:5n-6. The molecular species from which the lost polyenes originated were thus a trait of germ cells. A transient peak of 16:0-ceramide was observed 48 h after the single dose. In both doxorubicin regimes, sphingomyelin and ceramide with reduced amounts of VLCPUFA after about 4 weeks and with no VLCPUFA after 9 weeks resulted. By contrast, triglycerides and especially cholesterol esters (CE) tended to accumulate in the testes undergoing germ cell death, probably in the surviving Sertoli cells, their fatty acid patterns suggesting that initially, these lipids retained part of the PUFA coming from, or no longer used for, the synthesis of germ cell glycerophospholipids. As the latter decreased, CE accumulated massively 9 weeks after starting doxorubicin treatment, 20:4n-6 becoming their major PUFA. Part of these CEs may derive from surviving steroidogenic cells.
Samanta R Zanetti; Eduardo N Maldonado; Marta I Aveldaño
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Cancer research     Volume:  67     ISSN:  0008-5472     ISO Abbreviation:  Cancer Res.     Publication Date:  2007 Jul 
Date Detail:
Created Date:  2007-07-19     Completed Date:  2007-08-21     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  2984705R     Medline TA:  Cancer Res     Country:  United States    
Other Details:
Languages:  eng     Pagination:  6973-80     Citation Subset:  IM    
Instituto de Investigaciones Bioquímicas de Bahía Blanca, Consejo Nacional de investigaciones Científicas y Técnicas y Universidad Nacional del Sur, La Carrindanga km. 7, 8000 Bahía Blanca, Argentina.
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MeSH Terms
Antibiotics, Antineoplastic / pharmacology*
Cholesterol Esters / chemistry
Doxorubicin / pharmacology*
Fatty Acids, Unsaturated / chemistry*
Glycerophospholipids / chemistry
Lipid Metabolism
Lipids / chemistry*
Rats, Wistar
Sertoli Cells / metabolism
Sphingomyelins / metabolism
Testis / metabolism*
Time Factors
Reg. No./Substance:
0/Antibiotics, Antineoplastic; 0/Cholesterol Esters; 0/Fatty Acids, Unsaturated; 0/Glycerophospholipids; 0/Lipids; 0/Sphingomyelins; 23214-92-8/Doxorubicin

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