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Simvastatin mitigates increases in risk factors for and the occurrence of cardiac disease following 10 Gy total body irradiation.

Lenarczyk M, Su J, Haworth ST, Komorowski R, Fish BL, Migrino RQ, Harmann L, Hopewell JW, Kronenberg A, Patel S, Moulder JE, Baker JE - Pharmacol Res Perspect (2015)

Bottom Line: TBI resulted in cellular peri-arterial fibrosis, whereas control hearts had less collagen and fibrosis.Simvastatin mitigated these morphological injuries.Simvastatin mitigated the severity of this myocardial infarction at 20 and 80 days following TBI.

View Article: PubMed Central - PubMed

Affiliation: Division of Cardiothoracic Surgery, Medical College of Wisconsin Milwaukee, Wisconsin.

ABSTRACT
The ability of simvastatin to mitigate the increases in risk factors for and the occurrence of cardiac disease after 10 Gy total body irradiation (TBI) was determined. This radiation dose is relevant to conditioning for stem cell transplantation and threats from radiological terrorism. Male rats received single dose TBI of 10 Gy. Age-matched, sham-irradiated rats served as controls. Lipid profile, heart and liver morphology and cardiac mechanical function were determined for up to 120 days after irradiation. TBI resulted in a sustained increase in total- and LDL-cholesterol (low-density lipoprotein-cholesterol), and triglycerides. Simvastatin (10 mg/kg body weight/day) administered continuously from 9 days after irradiation mitigated TBI-induced increases in total- and LDL-cholesterol and triglycerides, as well as liver injury. TBI resulted in cellular peri-arterial fibrosis, whereas control hearts had less collagen and fibrosis. Simvastatin mitigated these morphological injuries. TBI resulted in cardiac mechanical dysfunction. Simvastatin mitigated cardiac mechanical dysfunction 20-120 days following TBI. To determine whether simvastatin affects the ability of the heart to withstand stress after TBI, injury from myocardial ischemia/reperfusion was determined in vitro. TBI increased the severity of an induced myocardial infarction at 20 and 80 days after irradiation. Simvastatin mitigated the severity of this myocardial infarction at 20 and 80 days following TBI. It is concluded simvastatin mitigated the increases in risk factors for cardiac disease and the extent of cardiac disease following TBI. This statin may be developed as a medical countermeasure for the mitigation of radiation-induced cardiac disease.

No MeSH data available.


Related in: MedlinePlus

Simvastatin mitigates increases in risk factors for (A) cardiac disease and (B) kidney injury. Time-related changes in total cholesterol, triglycerides, LDL-cholesterol, HDLcholesterol, BUN and creatinine after TBI () and the impact of simvastatin (Sim) alone () or in combination with TBI () compared with age-matched, sham-irradiated controls (▲). Data shown as means + SD, n = 9–15/group. #P < 0.05, Sim vs. control, *P < 0.05, TBI vs. TBI + Sim. LDL, low-density lipoprotein; HDL, high density lipoprotein; BUN, blood urea nitrogen; TBI, total body irradiation.
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fig01: Simvastatin mitigates increases in risk factors for (A) cardiac disease and (B) kidney injury. Time-related changes in total cholesterol, triglycerides, LDL-cholesterol, HDLcholesterol, BUN and creatinine after TBI () and the impact of simvastatin (Sim) alone () or in combination with TBI () compared with age-matched, sham-irradiated controls (▲). Data shown as means + SD, n = 9–15/group. #P < 0.05, Sim vs. control, *P < 0.05, TBI vs. TBI + Sim. LDL, low-density lipoprotein; HDL, high density lipoprotein; BUN, blood urea nitrogen; TBI, total body irradiation.

Mentions: From >60 days after TBI, the total cholesterol, LDL-cholesterol and triglyceride levels were significantly elevated compared to those in age-matched sham-irradiated control rats. In sham-irradiated rats, simvastatin alone significantly decreased total cholesterol levels at 20 days after the start of the study and throughout the duration of the study (Fig.1A). From 80 to 120 days after TBI, simvastatin consistently mitigated this increase in total cholesterol (Fig.1A). At these time intervals, simvastatin administration after TBI also reduced the increase in LDL-cholesterol, triglyceride levels, and HDL cholesterol levels compared with TBI alone. There were no mortalities in irradiated or sham-irradiated groups over the 120 day study period.


Simvastatin mitigates increases in risk factors for and the occurrence of cardiac disease following 10 Gy total body irradiation.

Lenarczyk M, Su J, Haworth ST, Komorowski R, Fish BL, Migrino RQ, Harmann L, Hopewell JW, Kronenberg A, Patel S, Moulder JE, Baker JE - Pharmacol Res Perspect (2015)

Simvastatin mitigates increases in risk factors for (A) cardiac disease and (B) kidney injury. Time-related changes in total cholesterol, triglycerides, LDL-cholesterol, HDLcholesterol, BUN and creatinine after TBI () and the impact of simvastatin (Sim) alone () or in combination with TBI () compared with age-matched, sham-irradiated controls (▲). Data shown as means + SD, n = 9–15/group. #P < 0.05, Sim vs. control, *P < 0.05, TBI vs. TBI + Sim. LDL, low-density lipoprotein; HDL, high density lipoprotein; BUN, blood urea nitrogen; TBI, total body irradiation.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4492761&req=5

fig01: Simvastatin mitigates increases in risk factors for (A) cardiac disease and (B) kidney injury. Time-related changes in total cholesterol, triglycerides, LDL-cholesterol, HDLcholesterol, BUN and creatinine after TBI () and the impact of simvastatin (Sim) alone () or in combination with TBI () compared with age-matched, sham-irradiated controls (▲). Data shown as means + SD, n = 9–15/group. #P < 0.05, Sim vs. control, *P < 0.05, TBI vs. TBI + Sim. LDL, low-density lipoprotein; HDL, high density lipoprotein; BUN, blood urea nitrogen; TBI, total body irradiation.
Mentions: From >60 days after TBI, the total cholesterol, LDL-cholesterol and triglyceride levels were significantly elevated compared to those in age-matched sham-irradiated control rats. In sham-irradiated rats, simvastatin alone significantly decreased total cholesterol levels at 20 days after the start of the study and throughout the duration of the study (Fig.1A). From 80 to 120 days after TBI, simvastatin consistently mitigated this increase in total cholesterol (Fig.1A). At these time intervals, simvastatin administration after TBI also reduced the increase in LDL-cholesterol, triglyceride levels, and HDL cholesterol levels compared with TBI alone. There were no mortalities in irradiated or sham-irradiated groups over the 120 day study period.

Bottom Line: TBI resulted in cellular peri-arterial fibrosis, whereas control hearts had less collagen and fibrosis.Simvastatin mitigated these morphological injuries.Simvastatin mitigated the severity of this myocardial infarction at 20 and 80 days following TBI.

View Article: PubMed Central - PubMed

Affiliation: Division of Cardiothoracic Surgery, Medical College of Wisconsin Milwaukee, Wisconsin.

ABSTRACT
The ability of simvastatin to mitigate the increases in risk factors for and the occurrence of cardiac disease after 10 Gy total body irradiation (TBI) was determined. This radiation dose is relevant to conditioning for stem cell transplantation and threats from radiological terrorism. Male rats received single dose TBI of 10 Gy. Age-matched, sham-irradiated rats served as controls. Lipid profile, heart and liver morphology and cardiac mechanical function were determined for up to 120 days after irradiation. TBI resulted in a sustained increase in total- and LDL-cholesterol (low-density lipoprotein-cholesterol), and triglycerides. Simvastatin (10 mg/kg body weight/day) administered continuously from 9 days after irradiation mitigated TBI-induced increases in total- and LDL-cholesterol and triglycerides, as well as liver injury. TBI resulted in cellular peri-arterial fibrosis, whereas control hearts had less collagen and fibrosis. Simvastatin mitigated these morphological injuries. TBI resulted in cardiac mechanical dysfunction. Simvastatin mitigated cardiac mechanical dysfunction 20-120 days following TBI. To determine whether simvastatin affects the ability of the heart to withstand stress after TBI, injury from myocardial ischemia/reperfusion was determined in vitro. TBI increased the severity of an induced myocardial infarction at 20 and 80 days after irradiation. Simvastatin mitigated the severity of this myocardial infarction at 20 and 80 days following TBI. It is concluded simvastatin mitigated the increases in risk factors for cardiac disease and the extent of cardiac disease following TBI. This statin may be developed as a medical countermeasure for the mitigation of radiation-induced cardiac disease.

No MeSH data available.


Related in: MedlinePlus