Ameliorative effect of captopril against 5-fluorouracil-induced cardiotoxicity in rats: A study with the light and electron microscopes
Abd-Ellah, Hala;
Abstract
The chemotherapeutic agent 5-fluorouracil (5-FU) is a widely accepted part of many cancer treatment
protocols. Its cardiotoxic potential is known, but considered uncommon and usually not life-threatening,
although some cases of severe cardiotoxicity related to 5-FU have been reported. The objective of this study was
to determine the effectiveness of captopril, an angiotensin-converting enzyme (ACE) inhibitor containing
sulphydryl (-SH) group, in alleviating 5-FU-induced cardiotoxicity in male rats. Forty adult male rats were
assigned to four equal groups: Group I, rats received normal saline solution (control group); Group II, rats
received 5-FU 20 mg /kg/day, intraperitoneally for 5 days (5-FU alone group); Group III, rats received captopril
20 mg /kg/day, orally for 14 days (captopril alone group); Group IV, rats received 5-FU 20 mg /kg/day,
intraperitoneally for 5 days + captopril 20 mg /kg/day, orally for 14 days (5-FU + captopril group). Animals of
all groups were sacrificed and tissue samples from the cardiac muscle were taken and processed for both light
and electron microscopical examination. Light microscopic observations revealed that administration of 5-FU
caused variable signs of cardiotoxicity which are represented by focal atrophy, vacuolar degeneration,
coagulative necrosis as well as cytolysis of myocytes. Interstitial oedema together with inflammatory cell
infiltration in between the damaged myocardiocytes was also observed. Ultrastructural examination of these
specimens confirmed the light microscopic findings and demonstrated abnormal-shaped mitochondria, dilated
sarcoplasmic reticulum, interrupted Z lines and disorganization of the ordered parallel myofibrillar array.
Pretreatment with captopril and its concomitant administration with 5-FU for 14 days attenuated 5-FU-induced
myocardial damage and effectively reverted the abnormal structural changes to near normalcy. In conclusion,
these results suggest that captopril has a protective potential in ameliorating 5-FU-induced cardiotoxicity.
protocols. Its cardiotoxic potential is known, but considered uncommon and usually not life-threatening,
although some cases of severe cardiotoxicity related to 5-FU have been reported. The objective of this study was
to determine the effectiveness of captopril, an angiotensin-converting enzyme (ACE) inhibitor containing
sulphydryl (-SH) group, in alleviating 5-FU-induced cardiotoxicity in male rats. Forty adult male rats were
assigned to four equal groups: Group I, rats received normal saline solution (control group); Group II, rats
received 5-FU 20 mg /kg/day, intraperitoneally for 5 days (5-FU alone group); Group III, rats received captopril
20 mg /kg/day, orally for 14 days (captopril alone group); Group IV, rats received 5-FU 20 mg /kg/day,
intraperitoneally for 5 days + captopril 20 mg /kg/day, orally for 14 days (5-FU + captopril group). Animals of
all groups were sacrificed and tissue samples from the cardiac muscle were taken and processed for both light
and electron microscopical examination. Light microscopic observations revealed that administration of 5-FU
caused variable signs of cardiotoxicity which are represented by focal atrophy, vacuolar degeneration,
coagulative necrosis as well as cytolysis of myocytes. Interstitial oedema together with inflammatory cell
infiltration in between the damaged myocardiocytes was also observed. Ultrastructural examination of these
specimens confirmed the light microscopic findings and demonstrated abnormal-shaped mitochondria, dilated
sarcoplasmic reticulum, interrupted Z lines and disorganization of the ordered parallel myofibrillar array.
Pretreatment with captopril and its concomitant administration with 5-FU for 14 days attenuated 5-FU-induced
myocardial damage and effectively reverted the abnormal structural changes to near normalcy. In conclusion,
these results suggest that captopril has a protective potential in ameliorating 5-FU-induced cardiotoxicity.
Other data
Title | Ameliorative effect of captopril against 5-fluorouracil-induced cardiotoxicity in rats: A study with the light and electron microscopes | Authors | Abd-Ellah, Hala | Issue Date | Feb-2012 | Journal | Journal of Applied Sciences Research | DOI | http://www.scopus.com/inward/record.url?eid=2-s2.0-84860738006&partnerID=MN8TOARS http://www.scopus.com/inward/record.url?eid=2-s2.0-84860738006&partnerID=MN8TOARS |
Scopus ID | 2-s2.0-84860738006 |
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