Propionyl-L-Carnitine is Efficacious in Ulcerative Colitis Through its Action on the Immune Function and Microvasculature
Authors: Daniela Passeri
Gaetana Costanza
Silvia Pace
Elena Doldo
Katia Lombardo
Roberto Camerini
Paolo Fociani
Gaetano Arcuri
Maria Antonietta Stasi
Augusto Orlandi
Maria Giovanna Scioli
Franco Borsini
Journal: Clinical and Translational Gastroenterology (2014)
Discipline: CLINICAL MEDICINE
Keywords: Microvascular endothelial dysfunction; Ulcerative colitis; Propionyl-L-carnitine; Inflammation; Cell adhesion molecules
Affiliations: Anatomic Pathology, Tor Vergata University, Rome, Italy., Sigma-Tau, Pomezia, Rome, Italy., Anatomic Pathology, Luigi Sacco Hospital, Milan, Italy., Experimental Medicine and Biochemical Sciences, Tor Vergata University of Rome, Rome, Italy.

Abstract:  Objectives: Microvascular endothelial dysfunction characterizes ulcerative colitis (UC), the most widespread form of inflammatory bowel disease. Intestinal mucosal microvessels in UC display aberrant expression of cell adhesion molecules (CAMs) and increased inflammatory cell recruitment. Propionyl-L-carnitine (PLC), an ester of L-carnitine required for the mitochondrial transport of fatty acids, ameliorates propionyl-CoA bioavailability and reduces oxidative stress in ischemic tissues. The present study aimed to document the efficacy of anti-oxidative stress properties of PLC in counteracting intestinal microvascular endothelial dysfunction and inflammation. Methods: To evaluate the efficacy in vivo, we analyzed the effects in intestinal biopsies of patients with mild-to-moderate UC receiving oral PLC co-treatment and in rat TNBS-induced colitis; in addition, we investigated antioxidant PLC action in TNF-Œ±-stimulated human intestinal microvascular endothelial cells (HIMECs) in vitro. Results: Four-week PLC co-treatment reduced intestinal mucosal polymorph infiltration and CD4(+) lymphocytes, ICAM-1(+) and iNOS(+) microvessels compared with placebo-treated patients with UC. Oral and intrarectal administration of PLC but not L-carnitine or propionate reduced intestinal damage and microvascular dysfunction in rat TNBS-induced acute and reactivated colitis. In cultured TNF-Œ±-stimulated HIMECs, PLC restored Œ≤-oxidation and counteracted NADPH oxidase 4-generated oxidative stress-induced CAM expression and leukocyte adhesion. Inhibition of Œ≤-oxidation by L-aminocarnitine increased reactive oxygen species production and PLC beneficial effects on endothelial dysfunction and leukocyte adhesion. Finally, PLC reduced iNOS activity and nitric oxide accumulation in rat TNBS-induced colitis and in HIMEC cultures. Conclusions: Our results show that the beneficial antioxidant effect of PLC targeting intestinal microvasculature restores endothelial Œ≤-oxidation and function, and reduces mucosal inflammation in UC patients. 

Retracted: No

PubPeer comments:
 image duplication  Disclaimer: These potential image duplications have been detected automatically using ImageTwin http: dx.doi.org 10.1145 3019612.3019875 Although results have been curated, the automatic algorithm may have generated false positive results and cannot take into account all scientific explanations for apparent duplications like stripped and reprobed blots, time series, serial sections and reused controls. ,