Prophylactic role of acetyl-l-carnitine on knee lesions and associated pain in a rat model of osteoarthritis.
OBJECTIVE
in the present study, our aim was to validate in vivo the prophylactic role of acetyl-l-carnitine (ALC) using an established knee osteoarthritis (OA) animal model which mimics the pathological changes of OA in humans, targeting cartilage and causing chondrocyte death.


METHODS
animal model was obtained by an intra-articular injection of monosodium iodoacetate (MIA) into rat femorotibial joint space. Pain was measured in animals submitted to MIA model by paw pressure and compression behavioral tests in the presence or absence of ALC.


RESULTS
morphological analysis of knee-joint from MIA and ALC co-treated rats showed that the total pathological score attributed to histological findings was dramatically lower in rats treated with MIA in the presence of ALC. OA chondrocyte overexpression of pathogenic collagenase matrix-metallopeptidase-13 (MMP13) could be decreased in knee-cartilage from MIA/ALC rats; whereas type II collagen (COL2) expression level could be partially increased to control value. ALC twice daily treatment was able to attenuate pain in OA rat knee as revealed by mechanical behavioral tests.


CONCLUSIONS
in our experiments, pain that is usually associated with OA, was correlated with the severity of histopathological findings. Our findings show that there is a place for ALC as chondroprotective agents in cartilage degradation and strongly support the prophylactic and therapeutic potentials of ALC in knee-OA patients.
Department of Medicine, Surgery and Neuroscience, University of Siena, Siena, Italy; Siena University Medical School, Siena, Italy.
Enrica
E
Bianchi
Department of Neurosciences, Psychology, Drug Area and Child Health, NEUROFARBA, Pharmacology Unit, University of Florence, Florence, Italy.
Lorenzo
L
Di Cesare Mannelli
Siena University Medical School, Siena, Italy.
Cristina
C
Menicacci
Department of Medicine, Surgery and Neuroscience, University of Siena, Siena, Italy.
Paola
P
Lorenzoni
Department of Medicine, Surgery and Neuroscience, University of Siena, Siena, Italy.
Margherita
M
Aglianò
Department of Neurosciences, Psychology, Drug Area and Child Health, NEUROFARBA, Pharmacology Unit, University of Florence, Florence, Italy.
Carla
C
Ghelardini
D000108:Acetylcarnitine / Q000008:administration & dosage*; D000818:Animals; D019902:Chondrocytes / Q000187:drug effects / Q000473:pathology; D004195:Disease Models, Animal; D008297:Male; D020370:Osteoarthritis, Knee / Q000188:drug therapy* / Q000473:pathology; D010146:Pain / Q000188:drug therapy* / Q000473:pathology; D010147:Pain Measurement / Q000187:drug effects* / Q000379:methods; D051381:Rats; D017207:Rats, Sprague-Dawley
D000108:Acetylcarnitine
Acetyl-l-carnitine; Animal model; Chondrocyte; Osteoarthritis; Pain