Simvastatin improves sepsis-induced mortality and acute kidney injury via renal vascular effects
H Yasuda, P S T Yuen, X Hu, H Zhou, R A Star, H Yasuda, P S T Yuen, X Hu, H Zhou, R A Star
Abstract
Acute kidney injury (AKI) occurs in about half of patients in septic shock and the mortality of AKI with sepsis is extremely high. An effective therapeutic intervention is urgently required. Statins are 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors that also have pleiotropic actions. They have been reported to increase the survival of septic or infectious patients. But the effect of simvastatin, a widely used statin, on sepsis-induced AKI is unknown. The effects of simvastatin and tumor necrosis factor (TNF)-alpha neutralizing antibody were studied in a clinically relevant model of sepsis-induced AKI using cecal ligation and puncture (CLP) in elderly mice. Simvastatin significantly improved CLP-induced mortality and AKI. Simvastatin attenuated CLP-induced tubular damage and reversed CLP-induced reduction of intrarenal microvascular perfusion and renal tubular hypoxia at 24 h. Simvastatin also restored towards normal CLP-induced renal vascular protein leak and serum TNF-alpha. Neither delayed simvastatin therapy nor TNF-alpha neutralizing antibody improved CLP-induced AKI. Simvastatin improved sepsis-induced AKI by direct effects on the renal vasculature, reversal of tubular hypoxia, and had a systemic anti-inflammatory effect.
Figures
![Figure 1. Effect of simvastatin on survival…](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/2377392/bin/nihms42391f1.jpg)
Figure 2. Effect of simvastatin on renal…
Figure 2. Effect of simvastatin on renal function following surgery
Mice were treated as in…
Figure 3. Effect of simvastatin on renal…
Figure 3. Effect of simvastatin on renal histology
Mice were treated as in Figure 1.…
Figure 4. Effect of simvastatin on renal…
Figure 4. Effect of simvastatin on renal vascular permeability
Mice were treated as in Figure…
Figure 5. Effect of simvastatin on pimonidazole…
Figure 5. Effect of simvastatin on pimonidazole incorporation following surgery
Mice were treated as in…
Figure 6. Effect of simvastatin on renal…
Figure 6. Effect of simvastatin on renal microvascular perfusion following surgery
Mice were treated as…
Figure 7. Effect of simvastatin on serum…
Figure 7. Effect of simvastatin on serum TNF-alpha
Mice were treated as in Figure 1.…
Figure 8. Effect of TNF-alpha neutralizing antibody…
Figure 8. Effect of TNF-alpha neutralizing antibody on renal function following CLP surgery
TNF-alpha neutralizing…
- The Therapeutic Effects of Curcumin in Early Septic Acute Kidney Injury: An Experimental Study.Wang S, Zhao P, Zhang Y, Zhu L, Zhu J, Luo Y, Li Q. Wang S, et al. Drug Des Devel Ther. 2021 Oct 7;15:4243-4255. doi: 10.2147/DDDT.S332623. eCollection 2021. Drug Des Devel Ther. 2021. PMID: 34675487 Free PMC article.
- Xuebijing injection in septic rats mitigates kidney injury, reduces cortical microcirculatory disorders, and suppresses activation of local inflammation.Liu J, Wang Z, Lin J, Li T, Guo X, Pang R, Dong L, Duan M. Liu J, et al. J Ethnopharmacol. 2021 Aug 10;276:114199. doi: 10.1016/j.jep.2021.114199. Epub 2021 May 12. J Ethnopharmacol. 2021. PMID: 33989736
- Rolipram improves renal perfusion and function during sepsis in the mouse.Holthoff JH, Wang Z, Patil NK, Gokden N, Mayeux PR. Holthoff JH, et al. J Pharmacol Exp Ther. 2013 Nov;347(2):357-64. doi: 10.1124/jpet.113.208520. Epub 2013 Sep 9. J Pharmacol Exp Ther. 2013. PMID: 24018639 Free PMC article.
- Resveratrol improves renal microcirculation, protects the tubular epithelium, and prolongs survival in a mouse model of sepsis-induced acute kidney injury.Holthoff JH, Wang Z, Seely KA, Gokden N, Mayeux PR. Holthoff JH, et al. Kidney Int. 2012 Feb;81(4):370-8. doi: 10.1038/ki.2011.347. Epub 2011 Oct 5. Kidney Int. 2012. PMID: 21975863 Free PMC article.
- Polydatin Inhibits Mitochondrial Dysfunction in the Renal Tubular Epithelial Cells of a Rat Model of Sepsis-Induced Acute Kidney Injury.Gao Y, Zeng Z, Li T, Xu S, Wang X, Chen Z, Lin C. Gao Y, et al. Anesth Analg. 2015 Nov;121(5):1251-60. doi: 10.1213/ANE.0000000000000977. Anesth Analg. 2015. PMID: 26484460
- Association of Prior to Intensive Care Unit Statin Use With Outcomes on Patients With Acute Kidney Injury.Tu B, Tang Y, Cheng Y, Yang Y, Wu C, Liu X, Qian D, Zhang Z, Zhao Y, Qin Y, He J. Tu B, et al. Front Med (Lausanne). 2021 Dec 24;8:810651. doi: 10.3389/fmed.2021.810651. eCollection 2021. Front Med (Lausanne). 2021. PMID: 35004788 Free PMC article.
- Geniposide ameliorated sepsis-induced acute kidney injury by activating PPARγ.Liu J, Zhao N, Shi G, Wang H. Liu J, et al. Aging (Albany NY). 2020 Nov 10;12(22):22744-22758. doi: 10.18632/aging.103902. Epub 2020 Nov 10. Aging (Albany NY). 2020. PMID: 33197894 Free PMC article.
- Simvastatin Posttreatment Controls Inflammation and Improves Bacterial Clearance in Experimental Sepsis.de Jesus Oliveira FM, Gonçalves-de-Albuquerque CF, de Moraes IMM, Reis PA, Rocha VN, Bozza PT, Silva AR, de Castro Faria Neto HC. de Jesus Oliveira FM, et al. Mediators Inflamm. 2020 Oct 14;2020:1839762. doi: 10.1155/2020/1839762. eCollection 2020. Mediators Inflamm. 2020. PMID: 33110395 Free PMC article.
- Protective Effects of Simvastatin on Endotoxin-Induced Acute Kidney Injury through Activation of Tubular Epithelial Cells' Survival and Hindering Cytochrome C-Mediated Apoptosis.Nežić L, Škrbić R, Amidžić L, Gajanin R, Milovanović Z, Nepovimova E, Kuča K, Jaćević V. Nežić L, et al. Int J Mol Sci. 2020 Sep 30;21(19):7236. doi: 10.3390/ijms21197236. Int J Mol Sci. 2020. PMID: 33008033 Free PMC article.
- Serum irisin levels are decreased in patients with sepsis, and exogenous irisin suppresses ferroptosis in the liver of septic mice.Wei S, Bi J, Yang L, Zhang J, Wan Y, Chen X, Wang Y, Wu Z, Lv Y, Wu R. Wei S, et al. Clin Transl Med. 2020 Sep;10(5):e173. doi: 10.1002/ctm2.173. Clin Transl Med. 2020. PMID: 32997405 Free PMC article.
- Research Support, N.I.H., Intramural
- Acute Kidney Injury / drug therapy*
- Acute Kidney Injury / etiology
- Animals
- Antibodies / pharmacology
- Blood Vessels / drug effects
- Delayed-Action Preparations / administration & dosage
- Hypoxia / drug therapy
- Kidney Tubules / blood supply
- Kidney Tubules / drug effects
- Kidney Tubules / pathology
- Lipids / blood
- Male
- Mice
- Mice, Inbred C57BL
- Microcirculation / drug effects
- Permeability
- Renal Circulation / drug effects*
- Sepsis / complications
- Sepsis / drug therapy*
- Sepsis / metabolism
- Simvastatin / administration & dosage*
- Tumor Necrosis Factor-alpha / antagonists & inhibitors
- Tumor Necrosis Factor-alpha / metabolism
- Antibodies
- Delayed-Action Preparations
- Lipids
- Tumor Necrosis Factor-alpha
- Simvastatin
- Full Text Sources
- Other Literature Sources
- Medical
- Miscellaneous
NCBI Literature Resources
The PubMed wordmark and PubMed logo are registered trademarks of the U.S. Department of Health and Human Services (HHS). Unauthorized use of these marks is strictly prohibited.
National Library of Medicine
8600 Rockville Pike
Bethesda, MD 20894
![Figure 2. Effect of simvastatin on renal…](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/2377392/bin/nihms42391f2.jpg)
Figure 3. Effect of simvastatin on renal…
Figure 3. Effect of simvastatin on renal histology
Mice were treated as in Figure 1.…
Figure 4. Effect of simvastatin on renal…
Figure 4. Effect of simvastatin on renal vascular permeability
Mice were treated as in Figure…
Figure 5. Effect of simvastatin on pimonidazole…
Figure 5. Effect of simvastatin on pimonidazole incorporation following surgery
Mice were treated as in…
Figure 6. Effect of simvastatin on renal…
Figure 6. Effect of simvastatin on renal microvascular perfusion following surgery
Mice were treated as…
Figure 7. Effect of simvastatin on serum…
Figure 7. Effect of simvastatin on serum TNF-alpha
Mice were treated as in Figure 1.…
Figure 8. Effect of TNF-alpha neutralizing antibody…
Figure 8. Effect of TNF-alpha neutralizing antibody on renal function following CLP surgery
TNF-alpha neutralizing…
- The Therapeutic Effects of Curcumin in Early Septic Acute Kidney Injury: An Experimental Study.Wang S, Zhao P, Zhang Y, Zhu L, Zhu J, Luo Y, Li Q. Wang S, et al. Drug Des Devel Ther. 2021 Oct 7;15:4243-4255. doi: 10.2147/DDDT.S332623. eCollection 2021. Drug Des Devel Ther. 2021. PMID: 34675487 Free PMC article.
- Xuebijing injection in septic rats mitigates kidney injury, reduces cortical microcirculatory disorders, and suppresses activation of local inflammation.Liu J, Wang Z, Lin J, Li T, Guo X, Pang R, Dong L, Duan M. Liu J, et al. J Ethnopharmacol. 2021 Aug 10;276:114199. doi: 10.1016/j.jep.2021.114199. Epub 2021 May 12. J Ethnopharmacol. 2021. PMID: 33989736
- Rolipram improves renal perfusion and function during sepsis in the mouse.Holthoff JH, Wang Z, Patil NK, Gokden N, Mayeux PR. Holthoff JH, et al. J Pharmacol Exp Ther. 2013 Nov;347(2):357-64. doi: 10.1124/jpet.113.208520. Epub 2013 Sep 9. J Pharmacol Exp Ther. 2013. PMID: 24018639 Free PMC article.
- Resveratrol improves renal microcirculation, protects the tubular epithelium, and prolongs survival in a mouse model of sepsis-induced acute kidney injury.Holthoff JH, Wang Z, Seely KA, Gokden N, Mayeux PR. Holthoff JH, et al. Kidney Int. 2012 Feb;81(4):370-8. doi: 10.1038/ki.2011.347. Epub 2011 Oct 5. Kidney Int. 2012. PMID: 21975863 Free PMC article.
- Polydatin Inhibits Mitochondrial Dysfunction in the Renal Tubular Epithelial Cells of a Rat Model of Sepsis-Induced Acute Kidney Injury.Gao Y, Zeng Z, Li T, Xu S, Wang X, Chen Z, Lin C. Gao Y, et al. Anesth Analg. 2015 Nov;121(5):1251-60. doi: 10.1213/ANE.0000000000000977. Anesth Analg. 2015. PMID: 26484460
- Association of Prior to Intensive Care Unit Statin Use With Outcomes on Patients With Acute Kidney Injury.Tu B, Tang Y, Cheng Y, Yang Y, Wu C, Liu X, Qian D, Zhang Z, Zhao Y, Qin Y, He J. Tu B, et al. Front Med (Lausanne). 2021 Dec 24;8:810651. doi: 10.3389/fmed.2021.810651. eCollection 2021. Front Med (Lausanne). 2021. PMID: 35004788 Free PMC article.
- Geniposide ameliorated sepsis-induced acute kidney injury by activating PPARγ.Liu J, Zhao N, Shi G, Wang H. Liu J, et al. Aging (Albany NY). 2020 Nov 10;12(22):22744-22758. doi: 10.18632/aging.103902. Epub 2020 Nov 10. Aging (Albany NY). 2020. PMID: 33197894 Free PMC article.
- Simvastatin Posttreatment Controls Inflammation and Improves Bacterial Clearance in Experimental Sepsis.de Jesus Oliveira FM, Gonçalves-de-Albuquerque CF, de Moraes IMM, Reis PA, Rocha VN, Bozza PT, Silva AR, de Castro Faria Neto HC. de Jesus Oliveira FM, et al. Mediators Inflamm. 2020 Oct 14;2020:1839762. doi: 10.1155/2020/1839762. eCollection 2020. Mediators Inflamm. 2020. PMID: 33110395 Free PMC article.
- Protective Effects of Simvastatin on Endotoxin-Induced Acute Kidney Injury through Activation of Tubular Epithelial Cells' Survival and Hindering Cytochrome C-Mediated Apoptosis.Nežić L, Škrbić R, Amidžić L, Gajanin R, Milovanović Z, Nepovimova E, Kuča K, Jaćević V. Nežić L, et al. Int J Mol Sci. 2020 Sep 30;21(19):7236. doi: 10.3390/ijms21197236. Int J Mol Sci. 2020. PMID: 33008033 Free PMC article.
- Serum irisin levels are decreased in patients with sepsis, and exogenous irisin suppresses ferroptosis in the liver of septic mice.Wei S, Bi J, Yang L, Zhang J, Wan Y, Chen X, Wang Y, Wu Z, Lv Y, Wu R. Wei S, et al. Clin Transl Med. 2020 Sep;10(5):e173. doi: 10.1002/ctm2.173. Clin Transl Med. 2020. PMID: 32997405 Free PMC article.
- Research Support, N.I.H., Intramural
- Acute Kidney Injury / drug therapy*
- Acute Kidney Injury / etiology
- Animals
- Antibodies / pharmacology
- Blood Vessels / drug effects
- Delayed-Action Preparations / administration & dosage
- Hypoxia / drug therapy
- Kidney Tubules / blood supply
- Kidney Tubules / drug effects
- Kidney Tubules / pathology
- Lipids / blood
- Male
- Mice
- Mice, Inbred C57BL
- Microcirculation / drug effects
- Permeability
- Renal Circulation / drug effects*
- Sepsis / complications
- Sepsis / drug therapy*
- Sepsis / metabolism
- Simvastatin / administration & dosage*
- Tumor Necrosis Factor-alpha / antagonists & inhibitors
- Tumor Necrosis Factor-alpha / metabolism
- Antibodies
- Delayed-Action Preparations
- Lipids
- Tumor Necrosis Factor-alpha
- Simvastatin
- Full Text Sources
- Other Literature Sources
- Medical
- Miscellaneous
NCBI Literature Resources
The PubMed wordmark and PubMed logo are registered trademarks of the U.S. Department of Health and Human Services (HHS). Unauthorized use of these marks is strictly prohibited.
National Library of Medicine
8600 Rockville Pike
Bethesda, MD 20894
![Figure 3. Effect of simvastatin on renal…](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/2377392/bin/nihms42391f3.jpg)
Figure 4. Effect of simvastatin on renal…
Figure 4. Effect of simvastatin on renal vascular permeability
Mice were treated as in Figure…
Figure 5. Effect of simvastatin on pimonidazole…
Figure 5. Effect of simvastatin on pimonidazole incorporation following surgery
Mice were treated as in…
Figure 6. Effect of simvastatin on renal…
Figure 6. Effect of simvastatin on renal microvascular perfusion following surgery
Mice were treated as…
Figure 7. Effect of simvastatin on serum…
Figure 7. Effect of simvastatin on serum TNF-alpha
Mice were treated as in Figure 1.…
Figure 8. Effect of TNF-alpha neutralizing antibody…
Figure 8. Effect of TNF-alpha neutralizing antibody on renal function following CLP surgery
TNF-alpha neutralizing…
- The Therapeutic Effects of Curcumin in Early Septic Acute Kidney Injury: An Experimental Study.Wang S, Zhao P, Zhang Y, Zhu L, Zhu J, Luo Y, Li Q. Wang S, et al. Drug Des Devel Ther. 2021 Oct 7;15:4243-4255. doi: 10.2147/DDDT.S332623. eCollection 2021. Drug Des Devel Ther. 2021. PMID: 34675487 Free PMC article.
- Xuebijing injection in septic rats mitigates kidney injury, reduces cortical microcirculatory disorders, and suppresses activation of local inflammation.Liu J, Wang Z, Lin J, Li T, Guo X, Pang R, Dong L, Duan M. Liu J, et al. J Ethnopharmacol. 2021 Aug 10;276:114199. doi: 10.1016/j.jep.2021.114199. Epub 2021 May 12. J Ethnopharmacol. 2021. PMID: 33989736
- Rolipram improves renal perfusion and function during sepsis in the mouse.Holthoff JH, Wang Z, Patil NK, Gokden N, Mayeux PR. Holthoff JH, et al. J Pharmacol Exp Ther. 2013 Nov;347(2):357-64. doi: 10.1124/jpet.113.208520. Epub 2013 Sep 9. J Pharmacol Exp Ther. 2013. PMID: 24018639 Free PMC article.
- Resveratrol improves renal microcirculation, protects the tubular epithelium, and prolongs survival in a mouse model of sepsis-induced acute kidney injury.Holthoff JH, Wang Z, Seely KA, Gokden N, Mayeux PR. Holthoff JH, et al. Kidney Int. 2012 Feb;81(4):370-8. doi: 10.1038/ki.2011.347. Epub 2011 Oct 5. Kidney Int. 2012. PMID: 21975863 Free PMC article.
- Polydatin Inhibits Mitochondrial Dysfunction in the Renal Tubular Epithelial Cells of a Rat Model of Sepsis-Induced Acute Kidney Injury.Gao Y, Zeng Z, Li T, Xu S, Wang X, Chen Z, Lin C. Gao Y, et al. Anesth Analg. 2015 Nov;121(5):1251-60. doi: 10.1213/ANE.0000000000000977. Anesth Analg. 2015. PMID: 26484460
- Association of Prior to Intensive Care Unit Statin Use With Outcomes on Patients With Acute Kidney Injury.Tu B, Tang Y, Cheng Y, Yang Y, Wu C, Liu X, Qian D, Zhang Z, Zhao Y, Qin Y, He J. Tu B, et al. Front Med (Lausanne). 2021 Dec 24;8:810651. doi: 10.3389/fmed.2021.810651. eCollection 2021. Front Med (Lausanne). 2021. PMID: 35004788 Free PMC article.
- Geniposide ameliorated sepsis-induced acute kidney injury by activating PPARγ.Liu J, Zhao N, Shi G, Wang H. Liu J, et al. Aging (Albany NY). 2020 Nov 10;12(22):22744-22758. doi: 10.18632/aging.103902. Epub 2020 Nov 10. Aging (Albany NY). 2020. PMID: 33197894 Free PMC article.
- Simvastatin Posttreatment Controls Inflammation and Improves Bacterial Clearance in Experimental Sepsis.de Jesus Oliveira FM, Gonçalves-de-Albuquerque CF, de Moraes IMM, Reis PA, Rocha VN, Bozza PT, Silva AR, de Castro Faria Neto HC. de Jesus Oliveira FM, et al. Mediators Inflamm. 2020 Oct 14;2020:1839762. doi: 10.1155/2020/1839762. eCollection 2020. Mediators Inflamm. 2020. PMID: 33110395 Free PMC article.
- Protective Effects of Simvastatin on Endotoxin-Induced Acute Kidney Injury through Activation of Tubular Epithelial Cells' Survival and Hindering Cytochrome C-Mediated Apoptosis.Nežić L, Škrbić R, Amidžić L, Gajanin R, Milovanović Z, Nepovimova E, Kuča K, Jaćević V. Nežić L, et al. Int J Mol Sci. 2020 Sep 30;21(19):7236. doi: 10.3390/ijms21197236. Int J Mol Sci. 2020. PMID: 33008033 Free PMC article.
- Serum irisin levels are decreased in patients with sepsis, and exogenous irisin suppresses ferroptosis in the liver of septic mice.Wei S, Bi J, Yang L, Zhang J, Wan Y, Chen X, Wang Y, Wu Z, Lv Y, Wu R. Wei S, et al. Clin Transl Med. 2020 Sep;10(5):e173. doi: 10.1002/ctm2.173. Clin Transl Med. 2020. PMID: 32997405 Free PMC article.
- Research Support, N.I.H., Intramural
- Acute Kidney Injury / drug therapy*
- Acute Kidney Injury / etiology
- Animals
- Antibodies / pharmacology
- Blood Vessels / drug effects
- Delayed-Action Preparations / administration & dosage
- Hypoxia / drug therapy
- Kidney Tubules / blood supply
- Kidney Tubules / drug effects
- Kidney Tubules / pathology
- Lipids / blood
- Male
- Mice
- Mice, Inbred C57BL
- Microcirculation / drug effects
- Permeability
- Renal Circulation / drug effects*
- Sepsis / complications
- Sepsis / drug therapy*
- Sepsis / metabolism
- Simvastatin / administration & dosage*
- Tumor Necrosis Factor-alpha / antagonists & inhibitors
- Tumor Necrosis Factor-alpha / metabolism
- Antibodies
- Delayed-Action Preparations
- Lipids
- Tumor Necrosis Factor-alpha
- Simvastatin
- Full Text Sources
- Other Literature Sources
- Medical
- Miscellaneous
NCBI Literature Resources
The PubMed wordmark and PubMed logo are registered trademarks of the U.S. Department of Health and Human Services (HHS). Unauthorized use of these marks is strictly prohibited.
National Library of Medicine
8600 Rockville Pike
Bethesda, MD 20894
![Figure 4. Effect of simvastatin on renal…](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/2377392/bin/nihms42391f4.jpg)
Figure 5. Effect of simvastatin on pimonidazole…
Figure 5. Effect of simvastatin on pimonidazole incorporation following surgery
Mice were treated as in…
Figure 6. Effect of simvastatin on renal…
Figure 6. Effect of simvastatin on renal microvascular perfusion following surgery
Mice were treated as…
Figure 7. Effect of simvastatin on serum…
Figure 7. Effect of simvastatin on serum TNF-alpha
Mice were treated as in Figure 1.…
Figure 8. Effect of TNF-alpha neutralizing antibody…
Figure 8. Effect of TNF-alpha neutralizing antibody on renal function following CLP surgery
TNF-alpha neutralizing…
- The Therapeutic Effects of Curcumin in Early Septic Acute Kidney Injury: An Experimental Study.Wang S, Zhao P, Zhang Y, Zhu L, Zhu J, Luo Y, Li Q. Wang S, et al. Drug Des Devel Ther. 2021 Oct 7;15:4243-4255. doi: 10.2147/DDDT.S332623. eCollection 2021. Drug Des Devel Ther. 2021. PMID: 34675487 Free PMC article.
- Xuebijing injection in septic rats mitigates kidney injury, reduces cortical microcirculatory disorders, and suppresses activation of local inflammation.Liu J, Wang Z, Lin J, Li T, Guo X, Pang R, Dong L, Duan M. Liu J, et al. J Ethnopharmacol. 2021 Aug 10;276:114199. doi: 10.1016/j.jep.2021.114199. Epub 2021 May 12. J Ethnopharmacol. 2021. PMID: 33989736
- Rolipram improves renal perfusion and function during sepsis in the mouse.Holthoff JH, Wang Z, Patil NK, Gokden N, Mayeux PR. Holthoff JH, et al. J Pharmacol Exp Ther. 2013 Nov;347(2):357-64. doi: 10.1124/jpet.113.208520. Epub 2013 Sep 9. J Pharmacol Exp Ther. 2013. PMID: 24018639 Free PMC article.
- Resveratrol improves renal microcirculation, protects the tubular epithelium, and prolongs survival in a mouse model of sepsis-induced acute kidney injury.Holthoff JH, Wang Z, Seely KA, Gokden N, Mayeux PR. Holthoff JH, et al. Kidney Int. 2012 Feb;81(4):370-8. doi: 10.1038/ki.2011.347. Epub 2011 Oct 5. Kidney Int. 2012. PMID: 21975863 Free PMC article.
- Polydatin Inhibits Mitochondrial Dysfunction in the Renal Tubular Epithelial Cells of a Rat Model of Sepsis-Induced Acute Kidney Injury.Gao Y, Zeng Z, Li T, Xu S, Wang X, Chen Z, Lin C. Gao Y, et al. Anesth Analg. 2015 Nov;121(5):1251-60. doi: 10.1213/ANE.0000000000000977. Anesth Analg. 2015. PMID: 26484460
- Association of Prior to Intensive Care Unit Statin Use With Outcomes on Patients With Acute Kidney Injury.Tu B, Tang Y, Cheng Y, Yang Y, Wu C, Liu X, Qian D, Zhang Z, Zhao Y, Qin Y, He J. Tu B, et al. Front Med (Lausanne). 2021 Dec 24;8:810651. doi: 10.3389/fmed.2021.810651. eCollection 2021. Front Med (Lausanne). 2021. PMID: 35004788 Free PMC article.
- Geniposide ameliorated sepsis-induced acute kidney injury by activating PPARγ.Liu J, Zhao N, Shi G, Wang H. Liu J, et al. Aging (Albany NY). 2020 Nov 10;12(22):22744-22758. doi: 10.18632/aging.103902. Epub 2020 Nov 10. Aging (Albany NY). 2020. PMID: 33197894 Free PMC article.
- Simvastatin Posttreatment Controls Inflammation and Improves Bacterial Clearance in Experimental Sepsis.de Jesus Oliveira FM, Gonçalves-de-Albuquerque CF, de Moraes IMM, Reis PA, Rocha VN, Bozza PT, Silva AR, de Castro Faria Neto HC. de Jesus Oliveira FM, et al. Mediators Inflamm. 2020 Oct 14;2020:1839762. doi: 10.1155/2020/1839762. eCollection 2020. Mediators Inflamm. 2020. PMID: 33110395 Free PMC article.
- Protective Effects of Simvastatin on Endotoxin-Induced Acute Kidney Injury through Activation of Tubular Epithelial Cells' Survival and Hindering Cytochrome C-Mediated Apoptosis.Nežić L, Škrbić R, Amidžić L, Gajanin R, Milovanović Z, Nepovimova E, Kuča K, Jaćević V. Nežić L, et al. Int J Mol Sci. 2020 Sep 30;21(19):7236. doi: 10.3390/ijms21197236. Int J Mol Sci. 2020. PMID: 33008033 Free PMC article.
- Serum irisin levels are decreased in patients with sepsis, and exogenous irisin suppresses ferroptosis in the liver of septic mice.Wei S, Bi J, Yang L, Zhang J, Wan Y, Chen X, Wang Y, Wu Z, Lv Y, Wu R. Wei S, et al. Clin Transl Med. 2020 Sep;10(5):e173. doi: 10.1002/ctm2.173. Clin Transl Med. 2020. PMID: 32997405 Free PMC article.
- Research Support, N.I.H., Intramural
- Acute Kidney Injury / drug therapy*
- Acute Kidney Injury / etiology
- Animals
- Antibodies / pharmacology
- Blood Vessels / drug effects
- Delayed-Action Preparations / administration & dosage
- Hypoxia / drug therapy
- Kidney Tubules / blood supply
- Kidney Tubules / drug effects
- Kidney Tubules / pathology
- Lipids / blood
- Male
- Mice
- Mice, Inbred C57BL
- Microcirculation / drug effects
- Permeability
- Renal Circulation / drug effects*
- Sepsis / complications
- Sepsis / drug therapy*
- Sepsis / metabolism
- Simvastatin / administration & dosage*
- Tumor Necrosis Factor-alpha / antagonists & inhibitors
- Tumor Necrosis Factor-alpha / metabolism
- Antibodies
- Delayed-Action Preparations
- Lipids
- Tumor Necrosis Factor-alpha
- Simvastatin
- Full Text Sources
- Other Literature Sources
- Medical
- Miscellaneous
NCBI Literature Resources
The PubMed wordmark and PubMed logo are registered trademarks of the U.S. Department of Health and Human Services (HHS). Unauthorized use of these marks is strictly prohibited.
National Library of Medicine
8600 Rockville Pike
Bethesda, MD 20894
![Figure 5. Effect of simvastatin on pimonidazole…](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/2377392/bin/nihms42391f5.jpg)
Figure 6. Effect of simvastatin on renal…
Figure 6. Effect of simvastatin on renal microvascular perfusion following surgery
Mice were treated as…
Figure 7. Effect of simvastatin on serum…
Figure 7. Effect of simvastatin on serum TNF-alpha
Mice were treated as in Figure 1.…
Figure 8. Effect of TNF-alpha neutralizing antibody…
Figure 8. Effect of TNF-alpha neutralizing antibody on renal function following CLP surgery
TNF-alpha neutralizing…
- The Therapeutic Effects of Curcumin in Early Septic Acute Kidney Injury: An Experimental Study.Wang S, Zhao P, Zhang Y, Zhu L, Zhu J, Luo Y, Li Q. Wang S, et al. Drug Des Devel Ther. 2021 Oct 7;15:4243-4255. doi: 10.2147/DDDT.S332623. eCollection 2021. Drug Des Devel Ther. 2021. PMID: 34675487 Free PMC article.
- Xuebijing injection in septic rats mitigates kidney injury, reduces cortical microcirculatory disorders, and suppresses activation of local inflammation.Liu J, Wang Z, Lin J, Li T, Guo X, Pang R, Dong L, Duan M. Liu J, et al. J Ethnopharmacol. 2021 Aug 10;276:114199. doi: 10.1016/j.jep.2021.114199. Epub 2021 May 12. J Ethnopharmacol. 2021. PMID: 33989736
- Rolipram improves renal perfusion and function during sepsis in the mouse.Holthoff JH, Wang Z, Patil NK, Gokden N, Mayeux PR. Holthoff JH, et al. J Pharmacol Exp Ther. 2013 Nov;347(2):357-64. doi: 10.1124/jpet.113.208520. Epub 2013 Sep 9. J Pharmacol Exp Ther. 2013. PMID: 24018639 Free PMC article.
- Resveratrol improves renal microcirculation, protects the tubular epithelium, and prolongs survival in a mouse model of sepsis-induced acute kidney injury.Holthoff JH, Wang Z, Seely KA, Gokden N, Mayeux PR. Holthoff JH, et al. Kidney Int. 2012 Feb;81(4):370-8. doi: 10.1038/ki.2011.347. Epub 2011 Oct 5. Kidney Int. 2012. PMID: 21975863 Free PMC article.
- Polydatin Inhibits Mitochondrial Dysfunction in the Renal Tubular Epithelial Cells of a Rat Model of Sepsis-Induced Acute Kidney Injury.Gao Y, Zeng Z, Li T, Xu S, Wang X, Chen Z, Lin C. Gao Y, et al. Anesth Analg. 2015 Nov;121(5):1251-60. doi: 10.1213/ANE.0000000000000977. Anesth Analg. 2015. PMID: 26484460
- Association of Prior to Intensive Care Unit Statin Use With Outcomes on Patients With Acute Kidney Injury.Tu B, Tang Y, Cheng Y, Yang Y, Wu C, Liu X, Qian D, Zhang Z, Zhao Y, Qin Y, He J. Tu B, et al. Front Med (Lausanne). 2021 Dec 24;8:810651. doi: 10.3389/fmed.2021.810651. eCollection 2021. Front Med (Lausanne). 2021. PMID: 35004788 Free PMC article.
- Geniposide ameliorated sepsis-induced acute kidney injury by activating PPARγ.Liu J, Zhao N, Shi G, Wang H. Liu J, et al. Aging (Albany NY). 2020 Nov 10;12(22):22744-22758. doi: 10.18632/aging.103902. Epub 2020 Nov 10. Aging (Albany NY). 2020. PMID: 33197894 Free PMC article.
- Simvastatin Posttreatment Controls Inflammation and Improves Bacterial Clearance in Experimental Sepsis.de Jesus Oliveira FM, Gonçalves-de-Albuquerque CF, de Moraes IMM, Reis PA, Rocha VN, Bozza PT, Silva AR, de Castro Faria Neto HC. de Jesus Oliveira FM, et al. Mediators Inflamm. 2020 Oct 14;2020:1839762. doi: 10.1155/2020/1839762. eCollection 2020. Mediators Inflamm. 2020. PMID: 33110395 Free PMC article.
- Protective Effects of Simvastatin on Endotoxin-Induced Acute Kidney Injury through Activation of Tubular Epithelial Cells' Survival and Hindering Cytochrome C-Mediated Apoptosis.Nežić L, Škrbić R, Amidžić L, Gajanin R, Milovanović Z, Nepovimova E, Kuča K, Jaćević V. Nežić L, et al. Int J Mol Sci. 2020 Sep 30;21(19):7236. doi: 10.3390/ijms21197236. Int J Mol Sci. 2020. PMID: 33008033 Free PMC article.
- Serum irisin levels are decreased in patients with sepsis, and exogenous irisin suppresses ferroptosis in the liver of septic mice.Wei S, Bi J, Yang L, Zhang J, Wan Y, Chen X, Wang Y, Wu Z, Lv Y, Wu R. Wei S, et al. Clin Transl Med. 2020 Sep;10(5):e173. doi: 10.1002/ctm2.173. Clin Transl Med. 2020. PMID: 32997405 Free PMC article.
- Research Support, N.I.H., Intramural
- Acute Kidney Injury / drug therapy*
- Acute Kidney Injury / etiology
- Animals
- Antibodies / pharmacology
- Blood Vessels / drug effects
- Delayed-Action Preparations / administration & dosage
- Hypoxia / drug therapy
- Kidney Tubules / blood supply
- Kidney Tubules / drug effects
- Kidney Tubules / pathology
- Lipids / blood
- Male
- Mice
- Mice, Inbred C57BL
- Microcirculation / drug effects
- Permeability
- Renal Circulation / drug effects*
- Sepsis / complications
- Sepsis / drug therapy*
- Sepsis / metabolism
- Simvastatin / administration & dosage*
- Tumor Necrosis Factor-alpha / antagonists & inhibitors
- Tumor Necrosis Factor-alpha / metabolism
- Antibodies
- Delayed-Action Preparations
- Lipids
- Tumor Necrosis Factor-alpha
- Simvastatin
- Full Text Sources
- Other Literature Sources
- Medical
- Miscellaneous
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![Figure 6. Effect of simvastatin on renal…](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/2377392/bin/nihms42391f6.jpg)
![Figure 7. Effect of simvastatin on serum…](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/2377392/bin/nihms42391f7.jpg)
Figure 8. Effect of TNF-alpha neutralizing antibody…
Figure 8. Effect of TNF-alpha neutralizing antibody on renal function following CLP surgery
TNF-alpha neutralizing…
- The Therapeutic Effects of Curcumin in Early Septic Acute Kidney Injury: An Experimental Study.Wang S, Zhao P, Zhang Y, Zhu L, Zhu J, Luo Y, Li Q. Wang S, et al. Drug Des Devel Ther. 2021 Oct 7;15:4243-4255. doi: 10.2147/DDDT.S332623. eCollection 2021. Drug Des Devel Ther. 2021. PMID: 34675487 Free PMC article.
- Xuebijing injection in septic rats mitigates kidney injury, reduces cortical microcirculatory disorders, and suppresses activation of local inflammation.Liu J, Wang Z, Lin J, Li T, Guo X, Pang R, Dong L, Duan M. Liu J, et al. J Ethnopharmacol. 2021 Aug 10;276:114199. doi: 10.1016/j.jep.2021.114199. Epub 2021 May 12. J Ethnopharmacol. 2021. PMID: 33989736
- Rolipram improves renal perfusion and function during sepsis in the mouse.Holthoff JH, Wang Z, Patil NK, Gokden N, Mayeux PR. Holthoff JH, et al. J Pharmacol Exp Ther. 2013 Nov;347(2):357-64. doi: 10.1124/jpet.113.208520. Epub 2013 Sep 9. J Pharmacol Exp Ther. 2013. PMID: 24018639 Free PMC article.
- Resveratrol improves renal microcirculation, protects the tubular epithelium, and prolongs survival in a mouse model of sepsis-induced acute kidney injury.Holthoff JH, Wang Z, Seely KA, Gokden N, Mayeux PR. Holthoff JH, et al. Kidney Int. 2012 Feb;81(4):370-8. doi: 10.1038/ki.2011.347. Epub 2011 Oct 5. Kidney Int. 2012. PMID: 21975863 Free PMC article.
- Polydatin Inhibits Mitochondrial Dysfunction in the Renal Tubular Epithelial Cells of a Rat Model of Sepsis-Induced Acute Kidney Injury.Gao Y, Zeng Z, Li T, Xu S, Wang X, Chen Z, Lin C. Gao Y, et al. Anesth Analg. 2015 Nov;121(5):1251-60. doi: 10.1213/ANE.0000000000000977. Anesth Analg. 2015. PMID: 26484460
- Association of Prior to Intensive Care Unit Statin Use With Outcomes on Patients With Acute Kidney Injury.Tu B, Tang Y, Cheng Y, Yang Y, Wu C, Liu X, Qian D, Zhang Z, Zhao Y, Qin Y, He J. Tu B, et al. Front Med (Lausanne). 2021 Dec 24;8:810651. doi: 10.3389/fmed.2021.810651. eCollection 2021. Front Med (Lausanne). 2021. PMID: 35004788 Free PMC article.
- Geniposide ameliorated sepsis-induced acute kidney injury by activating PPARγ.Liu J, Zhao N, Shi G, Wang H. Liu J, et al. Aging (Albany NY). 2020 Nov 10;12(22):22744-22758. doi: 10.18632/aging.103902. Epub 2020 Nov 10. Aging (Albany NY). 2020. PMID: 33197894 Free PMC article.
- Simvastatin Posttreatment Controls Inflammation and Improves Bacterial Clearance in Experimental Sepsis.de Jesus Oliveira FM, Gonçalves-de-Albuquerque CF, de Moraes IMM, Reis PA, Rocha VN, Bozza PT, Silva AR, de Castro Faria Neto HC. de Jesus Oliveira FM, et al. Mediators Inflamm. 2020 Oct 14;2020:1839762. doi: 10.1155/2020/1839762. eCollection 2020. Mediators Inflamm. 2020. PMID: 33110395 Free PMC article.
- Protective Effects of Simvastatin on Endotoxin-Induced Acute Kidney Injury through Activation of Tubular Epithelial Cells' Survival and Hindering Cytochrome C-Mediated Apoptosis.Nežić L, Škrbić R, Amidžić L, Gajanin R, Milovanović Z, Nepovimova E, Kuča K, Jaćević V. Nežić L, et al. Int J Mol Sci. 2020 Sep 30;21(19):7236. doi: 10.3390/ijms21197236. Int J Mol Sci. 2020. PMID: 33008033 Free PMC article.
- Serum irisin levels are decreased in patients with sepsis, and exogenous irisin suppresses ferroptosis in the liver of septic mice.Wei S, Bi J, Yang L, Zhang J, Wan Y, Chen X, Wang Y, Wu Z, Lv Y, Wu R. Wei S, et al. Clin Transl Med. 2020 Sep;10(5):e173. doi: 10.1002/ctm2.173. Clin Transl Med. 2020. PMID: 32997405 Free PMC article.
- Research Support, N.I.H., Intramural
- Acute Kidney Injury / drug therapy*
- Acute Kidney Injury / etiology
- Animals
- Antibodies / pharmacology
- Blood Vessels / drug effects
- Delayed-Action Preparations / administration & dosage
- Hypoxia / drug therapy
- Kidney Tubules / blood supply
- Kidney Tubules / drug effects
- Kidney Tubules / pathology
- Lipids / blood
- Male
- Mice
- Mice, Inbred C57BL
- Microcirculation / drug effects
- Permeability
- Renal Circulation / drug effects*
- Sepsis / complications
- Sepsis / drug therapy*
- Sepsis / metabolism
- Simvastatin / administration & dosage*
- Tumor Necrosis Factor-alpha / antagonists & inhibitors
- Tumor Necrosis Factor-alpha / metabolism
- Antibodies
- Delayed-Action Preparations
- Lipids
- Tumor Necrosis Factor-alpha
- Simvastatin
- Full Text Sources
- Other Literature Sources
- Medical
- Miscellaneous
![Figure 8. Effect of TNF-alpha neutralizing antibody…](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/2377392/bin/nihms42391f8.jpg)
Source: PubMed