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A Novel Angiotensin Type I Receptor Antagonist, Fimasartan, Prevents Doxorubicin-induced Cardiotoxicity in Rats.

Chang SA, Lim BK, Lee YJ, Hong MK, Choi JO, Jeon ES - J. Korean Med. Sci. (2015)

Bottom Line: We performed a preclinical experiment to evaluate the preventive effect of a novel ARB, fimasartan, in DOX-CMP.Hemodynamic assessment showed higher dP/dt in the High-fima group compared with the DOX-only group.A novel ARB, fimasartan, may prevent DOX-CMP and improve survival rate in a dose-dependent manner in a rat model of DOX-CMP and could be a treatment option for the prevention of DOX-CMP.

View Article: PubMed Central - PubMed

Affiliation: Division of Cardiology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea. ; Cardiovascular Imaging Center, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.

ABSTRACT
Angiotensin receptor blockers (ARBs) have organ-protective effects in heart failure and may be also effective in doxorubicin-induced cardiomyopathy (DOX-CMP); however, the efficacy of ARBs on the prevention of DOX-CMP have not been investigated. We performed a preclinical experiment to evaluate the preventive effect of a novel ARB, fimasartan, in DOX-CMP. All animals underwent echocardiography and were randomly assigned into three groups: treated daily with vehicle (DOX-only group, n=22), 5 mg/kg of fimasartan (Low-fima group, n=22), and 10 mg/kg of fimasartan (High-fima group, n=19). DOX was injected once a week for six weeks. Echocardiography and hemodynamic assessment was performed at the 8th week using a miniaturized conductance catheter. Survival rate of the High-fima group was greater (100%) than that of the Low-fima (75%) and DOX-only groups (50%). Echocardiography showed preserved left ventricular (LV) ejection fraction in the High-fima group, but not in the DOX-only group (P=0.002). LV dimensions increased in the DOX-only group; however, remodeling was attenuated in the Low-fima and High-fima groups. Hemodynamic assessment showed higher dP/dt in the High-fima group compared with the DOX-only group. A novel ARB, fimasartan, may prevent DOX-CMP and improve survival rate in a dose-dependent manner in a rat model of DOX-CMP and could be a treatment option for the prevention of DOX-CMP.

No MeSH data available.


Related in: MedlinePlus

General feature of treated animals. (A) Rats in Dox-only group show severe shedding and ascites. (B) In contrast, rats in the High-fima group show no shedding or ascites.
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Figure 4: General feature of treated animals. (A) Rats in Dox-only group show severe shedding and ascites. (B) In contrast, rats in the High-fima group show no shedding or ascites.

Mentions: Diarrhea and abdominal distension associated with a large amount of ascites were common in the DOX-only group (n=15 [68%] and n=11 [50%], Table 3); however, these conditions did not occur in the High-fima group. A small number of animals (n=6 [27%]) in the Low-fima group had diarrhea. Although none of the fimasartan-treated rats showed abdominal distension, a small amount of ascites was found in about a quarter of the rats treated with fimasartan when the abdominal walls were opened and the visceral space examined. Body weight at eight weeks was smallest in the DOX-only group. Severe anorexia, shedding, and eye discharge with conjunctival hemorrhage were also common in the DOX-only group. In contrast, rats in the High-fima group showed less anorexia and no shedding, eye discharge, or ascites (Table 3, Fig. 4).


A Novel Angiotensin Type I Receptor Antagonist, Fimasartan, Prevents Doxorubicin-induced Cardiotoxicity in Rats.

Chang SA, Lim BK, Lee YJ, Hong MK, Choi JO, Jeon ES - J. Korean Med. Sci. (2015)

General feature of treated animals. (A) Rats in Dox-only group show severe shedding and ascites. (B) In contrast, rats in the High-fima group show no shedding or ascites.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4414639&req=5

Figure 4: General feature of treated animals. (A) Rats in Dox-only group show severe shedding and ascites. (B) In contrast, rats in the High-fima group show no shedding or ascites.
Mentions: Diarrhea and abdominal distension associated with a large amount of ascites were common in the DOX-only group (n=15 [68%] and n=11 [50%], Table 3); however, these conditions did not occur in the High-fima group. A small number of animals (n=6 [27%]) in the Low-fima group had diarrhea. Although none of the fimasartan-treated rats showed abdominal distension, a small amount of ascites was found in about a quarter of the rats treated with fimasartan when the abdominal walls were opened and the visceral space examined. Body weight at eight weeks was smallest in the DOX-only group. Severe anorexia, shedding, and eye discharge with conjunctival hemorrhage were also common in the DOX-only group. In contrast, rats in the High-fima group showed less anorexia and no shedding, eye discharge, or ascites (Table 3, Fig. 4).

Bottom Line: We performed a preclinical experiment to evaluate the preventive effect of a novel ARB, fimasartan, in DOX-CMP.Hemodynamic assessment showed higher dP/dt in the High-fima group compared with the DOX-only group.A novel ARB, fimasartan, may prevent DOX-CMP and improve survival rate in a dose-dependent manner in a rat model of DOX-CMP and could be a treatment option for the prevention of DOX-CMP.

View Article: PubMed Central - PubMed

Affiliation: Division of Cardiology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea. ; Cardiovascular Imaging Center, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.

ABSTRACT
Angiotensin receptor blockers (ARBs) have organ-protective effects in heart failure and may be also effective in doxorubicin-induced cardiomyopathy (DOX-CMP); however, the efficacy of ARBs on the prevention of DOX-CMP have not been investigated. We performed a preclinical experiment to evaluate the preventive effect of a novel ARB, fimasartan, in DOX-CMP. All animals underwent echocardiography and were randomly assigned into three groups: treated daily with vehicle (DOX-only group, n=22), 5 mg/kg of fimasartan (Low-fima group, n=22), and 10 mg/kg of fimasartan (High-fima group, n=19). DOX was injected once a week for six weeks. Echocardiography and hemodynamic assessment was performed at the 8th week using a miniaturized conductance catheter. Survival rate of the High-fima group was greater (100%) than that of the Low-fima (75%) and DOX-only groups (50%). Echocardiography showed preserved left ventricular (LV) ejection fraction in the High-fima group, but not in the DOX-only group (P=0.002). LV dimensions increased in the DOX-only group; however, remodeling was attenuated in the Low-fima and High-fima groups. Hemodynamic assessment showed higher dP/dt in the High-fima group compared with the DOX-only group. A novel ARB, fimasartan, may prevent DOX-CMP and improve survival rate in a dose-dependent manner in a rat model of DOX-CMP and could be a treatment option for the prevention of DOX-CMP.

No MeSH data available.


Related in: MedlinePlus