RESEARCH ARTICLE Antioxidant, antinociceptive and anti-inflammatory activities of atorvastatin and rosuvastatin in various experimental models Mahesh M. Ghaisas • Prasad R. Dandawate • Suyash A. Zawar • Yogesh S. Ahire • Santosh P. Gandhi Received: 12 December 2009 / Accepted: 28 April 2010 / Published online: 8 June 2010 Ó Springer Basel AG 2010 Abstract The present study was planned to investigate the antioxidant, antinociceptive, and anti-inflammatory activities of atorvastatin and rosuvastatin (1, 3 and 10 mg/ kg, p.o.) in various animal models. The antinociceptive effect was assessed by chemically- (formalin, acetic acid) and thermally- (hot plate) induced nociception, while anti- inflammatory effect was evaluated using carrageenan-, formaldehyde-induced paw oedema and cotton pellet- induced granuloma. The effect of atorvastatin and rosu- vastatin on liver antioxidant enzymes like superoxide dismutase, glutathione, LPO, CAT along with the effect on lactate dehydrogenase (LDH) and alkaline phosphatase (ALP) was evaluated in the cotton pellet-induced granu- loma model. Atorvastatin and rosuvastatin showed significant decrease (p \ 0.05) in carrageenan- and form- aldehyde-induced rat paw oedema and reduced granuloma formation in the cotton pellet-induced granuloma method (p \ 0.01) while the levels of LDH and ALP were also significantly decreased (p \ 0.05). The liver antioxidant enzyme levels were found to be restored (p \ 0.05). Atorvastatin and rosuvastatin also showed antinociceptive activities (p \ 0.05 and p \ 0.01) in the acetic acid- and formalin-induced nociception in mice, while there was no significant activity in the hot plate method. The present findings suggest that atorvastatin and rosuvastatin possess dose-dependent antioxidant, analgesic, and anti-inflamma- tory activities. Keywords Atorvastatin  Rosuvastatin  Analgesic activity  Anti-inflammatory activity  Antioxidant activity Introduction Statins belong to a class of 3-hydroxy-3-methyl-glutaryl coenzyme A (HMGCoA) reductase inhibitors used for treatment of hypercholesterolemic conditions associated with hypertension (Downs et al. 1998). Most of the effects of statins other than lipid lowering activity have been cor- related with their anti-inflammatory effects as inflammation plays an important role in pathogenesis of various diseases like cancer, arthritis, and Alzheimer’s disease. Statins were found to inhibit C-reactive protein which is a major marker of inflammation (Taubes 2002). Various reviews were published in recent years underlining the evidence of anti- inflammatory effects of statins (Weitz-Schmidt 2002; Scho ¨ nbeck and Libby 2004; Merx and Weber 2008). Statins were found to show their anti-inflammatory activity by inhibition of various mediators of inflammation like inter- leukins (IL-1, 2, 4, 5, 10, 12), interferon-c, tumor necrosis factor-a (TNF-a), cyclo-oxygenase-2 (COX-2), thrombox- anes A 2 , thromboxanes B 2 , and enhanced synthesis of prostacyclin which may contribute to diminished platelet activation (Scho ¨nbeck and Libby 2004). Atorvastatin showed improvement in adjuvant-induced arthritis in rats (Barsante et al. 2005) and in artheroscle- rosis in apoE -/- mouse model via anti-inflammatory effects in vascular endothelium (Nachtigal et al. 2006). Atorvastatin showed anti-inflammatory action in apoE/ LDL (low density lipoprotein) receptor-double-knockout mice by inhibiting expression of monocyte chemotactic protein-1, vascular cell adhesion molecule-1 (VCAM-1), and intercellular cell adhesion molecule-1 (Nachtigal et al. M. M. Ghaisas (&) Indira College of Pharmacy, Tathawade, Pune, India e-mail: ghaisasmm@yahoo.com P. R. Dandawate  S. A. Zawar  Y. S. Ahire  S. P. Gandhi Department of Pharmacology, Pad. Dr. D. Y. Patil Institute of Pharmaceutical Sciences and Research, Pimpri, Pune, India Inflammopharmacol (2010) 18:169–177 DOI 10.1007/s10787-010-0044-6 Inflammopharmacology