Effect of atorvastatin, a HMG-CoA reductase inhibitor in monosodium iodoacetate-induced osteoarthritic pain: implication for osteoarthritis therapy.
BACKGROUND
Oxidative stress is one of the main causes of pain and cartilage degradation in osteoarthritis. This study on atorvastatin, a HMG-CoA reductase inhibitor used in the treatment of hypercholesterolemia and prevention of coronary heart disease aimed to investigate its effect on hyperalgesia and cartilage damage in monosodium iodoacetate (MIA)-induced osteoarthritis model in rats.


METHODS
Osteoarthritis was induced by a single intra-articular injection of 3mg MIA. After daily administration of atorvastatin (3, 10 and 30 mg/kg) for 20 days by oral gavage, pain was assessed on days 0, 1, 3, 7, 14 and 21. Histopathology of ipsilateral knee joint; oxidative markers and antioxidants in plasma were assessed on day 21.


RESULTS
Atorvastatin attenuated hyperalgesia. The increased level of lipid peroxidation, superoxide, protein carbonyl; decreased activity of catalase, glutathione-S-transferase, reduced glutathione and total thiol levels in MIA rats were restored to the normal levels, however, superoxide dismutase and nitric oxide levels remained unaltered by atorvastatin. Further, atorvastatin reduced the MIA-induced histopathological alteration in the knee joint.


CONCLUSIONS
Our study demonstrated that atorvastatin attenuates MIA-induced osteoarthritic pain and protect cartilage degradation through inhibition of oxidative stress suggesting its importance in osteoarthritic pain management.
Division of Pharmacology and Toxicology, Bareilly, India.
Nitya N
NN
Pathak
Division of Pharmacology and Toxicology, Bareilly, India.
Venkanna
V
Balaganur
Division of Pharmacology and Toxicology, Bareilly, India.
Madhu C
MC
Lingaraju
Division of Pharmacology and Toxicology, Bareilly, India.
Vinay
V
Kant
Division of Pharmacology and Toxicology, Bareilly, India.
Dhirendra
D
Kumar
Division of Pharmacology and Toxicology, Bareilly, India.
Dinesh
D
Kumar
Division of Pathology, Indian Veterinary Research Institute, Bareilly, India.
Anil K
AK
Sharma
Division of Pharmacology and Toxicology, Bareilly, India. Electronic address: sktandan@ivri.res.in.
Surendra K
SK
Tandan
D000818:Animals; D000069059:Atorvastatin / Q000494:pharmacology / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D007270:Injections, Intra-Articular; D019807:Iodoacetic Acid / Q000633:toxicity*; D008297:Male; D010003:Osteoarthritis / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology; D010146:Pain / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology; D010147:Pain Measurement / Q000187:drug effects / Q000379:methods; D051381:Rats; D017208:Rats, Wistar; D016896:Treatment Outcome
D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D000069059:Atorvastatin; D019807:Iodoacetic Acid
Atorvastatin; Hyperalgesia; Monosodium iodoacetate; Osteoarthritis; Oxidative stress