PMID- 16242830
OWN - NLM
STAT- MEDLINE
DCOM- 20060302
LR  - 20131121
IS  - 0300-483X (Print)
IS  - 0300-483X (Linking)
VI  - 217
IP  - 2-3
DP  - 2006 Jan 16
TI  - Influence of a low-molecular-weight heparin derivative on the nitric oxide levels 
      and apoptotic DNA damage in adriamycin-induced cardiac and renal toxicity.
PG  - 176-83
AB  - The spectrum of the anti-apoptotic potential of heparin is currently under 
      scrutiny in various tissues and under various pathological situations. In this 
      study, the role of a low-molecular-weight heparin derivative (LMWH), certoparin 
      in adriamycin-induced oxidative DNA damage has been evaluated in the cardiac and 
      renal tissues. Two groups of male albino rats of the Wistar strain (140+/-10 g) 
      received a single intravenous injection of adriamycin (7.5mg/kg), and one of them 
      received low-molecular-weight heparin (Certoparin Sodium, 300 microg/day/rat 
      s.c.) treatment, commencing on day 8, continued for a week. The nitrosative 
      stress in ADR cytotoxicity is indicated by the 1.51-fold cardiac and 2.36-fold 
      renal increase in reactive nitrogen species (RNS), while LMWH treatment restores 
      normalcy (p<0.001). The influence of LMWH on the pro-inflammatory and 
      pro-apoptotic cytokine, TNF-alpha was studied. Renal and cardiac levels of 
      TNF-alpha showed a significant rise (p<0.001) in the ADR cytotoxic group, while 
      the TNF-alpha values departed towards control levels in the LMWH treated group 
      (p<0.001). DNA damage indicated by the fragmentation pattern (agarose gel 
      electrophoresis) and the significantly increased comet tail length (p<0.001) 
      observed after alkaline single cell gel electrophoresis confirmed the toxicity 
      induced by ADR on DNA in the untreated group. In the LMWH-treated group, the 
      observation of intact DNA band after agarose gel electrophoresis, and the finding 
      of comet tail length being comparable with that of the control substantiated the 
      protection rendered by the LMWH, certoparin. In short, the results suggest that 
      the low-molecular-weight heparin derivative, certoparin exerts beneficial effects 
      on the nitrosative status, and on the biological macromolecules as DNA and 
      curtails the rise of the pro-apoptotic and pro-inflammatory cytokine, TNF-alpha 
      in the cardiac and renal tissues.
FAU - Deepa, P R
AU  - Deepa PR
AD  - Department of Medical Biochemistry, Dr. ALM Post Graduate Institute of Basic 
      Medical Sciences, University of Madras, Taramani, Chennai 600113, India. 
      dipa_pr@mailcity.com
FAU - Varalakshmi, P
AU  - Varalakshmi P
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20051020
PL  - Ireland
TA  - Toxicology
JT  - Toxicology
JID - 0361055
RN  - 0 (Antibiotics, Antineoplastic)
RN  - 0 (Anticoagulants)
RN  - 0 (Heparin, Low-Molecular-Weight)
RN  - 0 (Nitrites)
RN  - 0 (Reactive Nitrogen Species)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 31C4KY9ESH (Nitric Oxide)
RN  - 80168379AG (Doxorubicin)
SB  - IM
MH  - Animals
MH  - Antibiotics, Antineoplastic/toxicity
MH  - Anticoagulants/pharmacology
MH  - Apoptosis/drug effects
MH  - Comet Assay
MH  - *DNA Damage
MH  - DNA Fragmentation/drug effects
MH  - Doxorubicin/*toxicity
MH  - Electrophoresis, Agar Gel
MH  - Endothelium, Vascular/drug effects/metabolism
MH  - Heart/drug effects/physiopathology
MH  - Heart Diseases/chemically induced/*metabolism/pathology
MH  - Heparin, Low-Molecular-Weight/*pharmacology
MH  - Kidney/drug effects/metabolism/physiopathology
MH  - Kidney Diseases/chemically induced/*metabolism/pathology
MH  - Male
MH  - Nitric Oxide/*metabolism
MH  - Nitrites/blood
MH  - Rats
MH  - Rats, Wistar
MH  - Reactive Nitrogen Species/metabolism
MH  - Tumor Necrosis Factor-alpha/chemistry/metabolism
EDAT- 2005/10/26 09:00
MHDA- 2006/03/03 09:00
CRDT- 2005/10/26 09:00
PHST- 2005/08/24 00:00 [received]
PHST- 2005/09/12 00:00 [revised]
PHST- 2005/09/15 00:00 [accepted]
PHST- 2005/10/26 09:00 [pubmed]
PHST- 2006/03/03 09:00 [medline]
PHST- 2005/10/26 09:00 [entrez]
AID - S0300-483X(05)00459-2 [pii]
AID - 10.1016/j.tox.2005.09.009 [doi]
PST - ppublish
SO  - Toxicology. 2006 Jan 16;217(2-3):176-83. doi: 10.1016/j.tox.2005.09.009. Epub 
      2005 Oct 20.