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Oleanolic acid protects against gastrointestinal disturbances in the experimental autoimmune encephalomyelitis model of multiple sclerosis

AuthorsGutiérrez, Beatriz; Gallardo, Isabel; Hernández, Marita CSIC ORCID CVN ; Cabero, M. I.; Alvarez, Yolanda CSIC ORCID; Simon, Inmaculada; Téllez, Nieves; Nieto, María Luisa CSIC ORCID
Issue Date2018
Citation34th Congress of The European Committee for Treatment and Research in Multiple Sclerosis (2018)
Abstract[Background]: Multiple sclerosis (MS) is a chronic inflammatory demyelinating disease of the CNS, in which oxidative stress play important roles. Characteristic symptoms include motor and sensory deficits in addition to gastrointestinal (GI) disturbances which etiology is less understood. The triterpene, oleanolic acid (OA), has proven effective attenuating neurological signs and histopathological features of disease on a MS mice model (experimental autoimmune encephalomyelitis, EAE) via anti-oxidant and immunomodulatory mechanisms. Herein, we investigate GI manifestations associated to EAE as potential therapeutic target of OA.
[Aims]: To determine the efficacy of OA in the prevention of GI disturbances in EAE, with a focus on oxidative-stress.
[Methods]: C57/BL6 mice were MOG35-55-inmunized and treated with OA (25 mg/kg/day, i.p). On day 21, in selected sample, we performed s: i) macroscopic intestinal analysis, ii) fecal and cecal evaluation, iii) GI hormone quantification: motilin, and iv) oxidant/antioxidant status analysis: TBARS, FRAP and sestrin-3, a ROS disruptor.
[Results]: Histopathological analysis did not reveal significant differences in the relative colon length among mice of the different experimental groups (p>0.05). The fecal water content was lower in the EAE group (13% decrease, p< 0.001) than in the control group. Full caecum and cecal content were significantly increased in EAE mice in comparison with those of the control one. Low motilin levels were detected in serum from EAE mice, compared to healthy mice (161±18 and 538±45pg/ml, respectively; p<0.001); and a similar pattern was observed in colon samples. An inverse correlation was found between motilin and the clinical signs score (r=-0.6294, p<0.001). We found that OA treatment to EAE mice had a protective effect attenuating all these alterations. In addition, colon from OA-treated EAE mice showed 4.3 times more non-enzymatic antioxidants and 1.9 times more of the ROS disruptor sestrin-3, than untreated-EAE mice. Interestingly, in healthy mice, high levels of FRAP and sestrin-3 were observed in the OA-treated group, compared with untreated animals (p<0.001). These markers correlated with the lipid peroxidation levels (r=-0.694, p=0.0007; r=-0.696, p=0.0007; respectively) as well as with the clinical signs score.
[Conclusion]: Our data contribute to the idea that GI dysfunction influences MS pathogenesis, and provides new findings regarding the beneficial activity of OA in EAE.
DescriptionResumen del trabajo presentado al 34th Congress of The European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS), celebrado en Berlin (Alemania) del 10 al 12 de octubre de 2018.
Appears in Collections:(IBGM) Comunicaciones congresos
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