Lack of effect of oral administration of resveratrol in LPS-induced systemic inflammation
The high mortality index due to sepsis and the lack of an effective treatment requires the search for new compounds that can serve as therapy for this disease. Resveratrol, a well-known anti-inflammatory natural compound, might be a good candidate for the treatment of sepsis. The aim of this work was to study the effects of oral administration of resveratrol, before and after sepsis initiation, on inflammation markers in a murine model of endotoxin-induced sepsis.
Sprague–Dawley male rats were treated with resveratrol the 3 days prior to LPS administration and 45 min later. Hematological parameters, TNF-α, IL-1β and CINC-1, FRAP and TBARS levels were determined. Resveratrol and resveratrol-derived metabolites profile in plasma was compared after oral and intraperitoneal administration.
Oral treatment with resveratrol had no apparent systemic protective effects. However, resveratrol reduced the levels of lipid peroxidation in the small intestine and colon. Importantly, the administration of LPS caused a decrease in resveratrol absorption. When resveratrol bioavailability after i.p. administration was compared to that observed after oral administration, a different profile of resveratrol metabolites was found in plasma.
These results highlight the importance of studying the bioavailability of the assayed compounds in the experimental models used to be able to choose the best route of administration depending on the target organ and to determine which compounds or derived metabolites are effective treating the studied disease.
KeywordsPolyphenol Lipopolysaccharide endotoxin Sepsis Cytokines Bioavailability
- 3.Winters BD, Eberlein M, Leung J, Needham DM, Pronovost PJ, Sevransky JE (2010) Long-term mortality and quality of life in sepsis: a systematic review. Crit Care Med 38:1276–1283Google Scholar
- 7.Larrosa M, Yañéz-Gascón MJ, Selma MV, González-Sarrías A, Toti S, Cerón JJ, Tomás-Barberán F, Dolara P, Espín JC (2009) Effect of a low dose of dietary resveratrol on colon microbiota, inflammation and tissue damage in a DSS-induced colitis rat model. J Agric Food Chem 57:2211–2220CrossRefGoogle Scholar
- 14.Kubota S, Kurihara T, Mochimaru H, Satofuka S, Noda K, Ozawa Y, Oike Y, Ishida S, Tsubota K (2009) Prevention of ocular inflammation in endotoxin-induced uveitis with resveratrol by inhibiting oxidative damage and nuclear factor-kappaB activation. Invest Ophthalmol Vis Sci 50:3512–3519CrossRefGoogle Scholar
- 16.Larrosa M, González-Sarrías A, Yáñez-Gascón MJ, Selma MV, Azorín-Ortuño M, Toti S, Tomás-Barberán F, Dolara P, Espín JC (2010) Anti-inflammatory properties of a pomegranate extract and its metabolite urolithin-A in a colitis rat model and the effect of colon inflammation on phenolic metabolism. J Nutr Biochem 21:717–725CrossRefGoogle Scholar
- 17.Pyles LA, Stejskal EJ, Einzig S (1993) Spectrophotometric measurement of plasma 2-thiobarbituric acid-reactive substances in the presence of hemoglobin and bilirubin interference. Proc Soc Exp Biol Med 202:407–419Google Scholar
- 25.Ayala A, Herdon CD, Lehman DL, Ayala CA, Chaudry IH (1996) Differential induction of apoptosis in lymphoid tissues during sepsis: variation in onset, frequency, and the nature of the mediators. Blood 87:4261–4275Google Scholar
- 29.Birrell MA, McCluskie K, Wong S, Donnelly LE, Barnes PJ, Belvisi MG (2005) Resveratrol, an extract of red wine, inhibits lipopolysaccharide induced airway neutrophilia and inflammatory mediators through an NF-kappaB-independent mechanism. FASEB J 19:840–851Google Scholar
- 31.Breedveld P, Pluim D, Cipriani G, Dahlhaus F, van Eijndhoven MA, de Wolf CJ, Kuil A, Beijnen JH, Scheffer GL, Jansen G, Borst P, Schellens JH (2007) The effect of low pH on breast cancer resistance protein (ABCG2)-mediated transport of methotrexate, 7-hydroxymethotrexate, methotrexate diglutamate, folic acid, mitoxantrone, topotecan, and resveratrol in in vitro drug transport models. Mol Pharmacol 71:240–249CrossRefGoogle Scholar