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Low-dose treatment with atorvastatin leads to anti-oxidative and anti-inflammatory effects in diabetes mellitus.
Eur J Pharmacol. 2007 Aug 27; 569(3):204-11.EJ

Abstract

We investigated whether atorvastatin, given in a dose to low to influence the lipid profile, has any effect on oxidative stress, inflammation and endothelial function under streptozotocin-induced diabetic conditions. Diabetes mellitus was induced in male Sprague Dawley rats by a single injection of streptozotocin. Rats were treated chronically with atorvastatin (50 mg/kg/day; p.o.) or vehicle until day 48 and compared with controls. NAD(P)H activity, protein expression nuclear factor-kappaBp65 (NF-kappaBp65) and phosphorylation of the extracellular signal-regulated kinase (ERK1/2) were assessed in the quadriceps muscle. Protein and mRNA levels of intracellular and vascular adhesion molecules (ICAM-1, VCAM-1) and cytokines were measured by Taqman or immunohistochemistry staining, respectively. Endothelial function was investigated in vivo using the autoperfused hind limb model. Diabetic groups displayed similar severe hyperglycemia. Untreated diabetic rats showed enhanced NAD(P)H activity, activation of the ERK1/2/NF-kappaBp65-pathway, enhanced expression of cytokines and cellular adhesion molecules and impaired vascular function. Low-dose therapy by atorvastatin did not alter the lipid profile but led to a reduction of NAD(P)H activity (-28%, P<0.05) associated with reduced protein expression of NF-kappaBp65 (-53%, P<0.05) and phosphorylation of its regulator mitogen-activated protein kinase (MAPK) ERK1/2 in diabetic rats. Also inflammatory markers were reduced after atorvastatin treatment indexed by reduced mRNA expression of VCAM-1 (-24%), tumor necrosis factor alpha (-59%) and interleukin 1beta (-50%) and reduced ICAM-1 (-81%) and VCAM-1 (-74%) positive staining. These beneficial effects were associated with improved endothelium-dependent vasodilatation (maximal vasodilatation: +101%; P<0.05). Lipid-independent anti-oxidative and anti-inflammatory effects of low-dose atorvastatin involving the ERK1/2/NF-kappaB-pathway are sufficient to improve endothelial function under experimental diabetic conditions.

Authors+Show Affiliations

Department of Cardiology and Pneumology, Charité - Universitätsmedizin Berlin, Campus Benjamin Franklin, Hindenburgdamm 30, 12206 Berlin, Germany.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

17669395

Citation

Riad, Alexander, et al. "Low-dose Treatment With Atorvastatin Leads to Anti-oxidative and Anti-inflammatory Effects in Diabetes Mellitus." European Journal of Pharmacology, vol. 569, no. 3, 2007, pp. 204-11.
Riad A, Du J, Stiehl S, et al. Low-dose treatment with atorvastatin leads to anti-oxidative and anti-inflammatory effects in diabetes mellitus. Eur J Pharmacol. 2007;569(3):204-11.
Riad, A., Du, J., Stiehl, S., Westermann, D., Mohr, Z., Sobirey, M., Doehner, W., Adams, V., Pauschinger, M., Schultheiss, H. P., & Tschöpe, C. (2007). Low-dose treatment with atorvastatin leads to anti-oxidative and anti-inflammatory effects in diabetes mellitus. European Journal of Pharmacology, 569(3), 204-11.
Riad A, et al. Low-dose Treatment With Atorvastatin Leads to Anti-oxidative and Anti-inflammatory Effects in Diabetes Mellitus. Eur J Pharmacol. 2007 Aug 27;569(3):204-11. PubMed PMID: 17669395.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Low-dose treatment with atorvastatin leads to anti-oxidative and anti-inflammatory effects in diabetes mellitus. AU - Riad,Alexander, AU - Du,Jing, AU - Stiehl,Sebastian, AU - Westermann,Dirk, AU - Mohr,Zarah, AU - Sobirey,Meike, AU - Doehner,Wolfram, AU - Adams,Volker, AU - Pauschinger,Matthias, AU - Schultheiss,Heinz Peter, AU - Tschöpe,Carsten, Y1 - 2007/05/24/ PY - 2007/01/05/received PY - 2007/04/24/revised PY - 2007/04/25/accepted PY - 2007/8/3/pubmed PY - 2007/12/27/medline PY - 2007/8/3/entrez SP - 204 EP - 11 JF - European journal of pharmacology JO - Eur J Pharmacol VL - 569 IS - 3 N2 - We investigated whether atorvastatin, given in a dose to low to influence the lipid profile, has any effect on oxidative stress, inflammation and endothelial function under streptozotocin-induced diabetic conditions. Diabetes mellitus was induced in male Sprague Dawley rats by a single injection of streptozotocin. Rats were treated chronically with atorvastatin (50 mg/kg/day; p.o.) or vehicle until day 48 and compared with controls. NAD(P)H activity, protein expression nuclear factor-kappaBp65 (NF-kappaBp65) and phosphorylation of the extracellular signal-regulated kinase (ERK1/2) were assessed in the quadriceps muscle. Protein and mRNA levels of intracellular and vascular adhesion molecules (ICAM-1, VCAM-1) and cytokines were measured by Taqman or immunohistochemistry staining, respectively. Endothelial function was investigated in vivo using the autoperfused hind limb model. Diabetic groups displayed similar severe hyperglycemia. Untreated diabetic rats showed enhanced NAD(P)H activity, activation of the ERK1/2/NF-kappaBp65-pathway, enhanced expression of cytokines and cellular adhesion molecules and impaired vascular function. Low-dose therapy by atorvastatin did not alter the lipid profile but led to a reduction of NAD(P)H activity (-28%, P<0.05) associated with reduced protein expression of NF-kappaBp65 (-53%, P<0.05) and phosphorylation of its regulator mitogen-activated protein kinase (MAPK) ERK1/2 in diabetic rats. Also inflammatory markers were reduced after atorvastatin treatment indexed by reduced mRNA expression of VCAM-1 (-24%), tumor necrosis factor alpha (-59%) and interleukin 1beta (-50%) and reduced ICAM-1 (-81%) and VCAM-1 (-74%) positive staining. These beneficial effects were associated with improved endothelium-dependent vasodilatation (maximal vasodilatation: +101%; P<0.05). Lipid-independent anti-oxidative and anti-inflammatory effects of low-dose atorvastatin involving the ERK1/2/NF-kappaB-pathway are sufficient to improve endothelial function under experimental diabetic conditions. SN - 0014-2999 UR - https://www.unboundmedicine.com/medline/citation/17669395/Low_dose_treatment_with_atorvastatin_leads_to_anti_oxidative_and_anti_inflammatory_effects_in_diabetes_mellitus_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0014-2999(07)00532-8 DB - PRIME DP - Unbound Medicine ER -