EFFECT OF A FERMENTED NUTRACEUTICAL ON THIOREDOXIN LEVEL AND TNF-α SIGNALLING IN CIRRHOTIC PATIENTS
F. MAROTTA, D.H. CHUI(1), S. JAIN(2), A. POLIMENI, K. KOIKE(3), L. ZHOU(1), A. LORENZETTI, H. SHIMIZU(3) and H. YANG(1)
ReGenera Research Group for Aging-Intervention, Milan, Italy
(1)Neuroscience Research Institute, Peking University, Health Science Center, China
(2)Department of Food Science and Human Nutrition, University of Illinois, Urbana-Champaign, USA
(3)Osato Research Institute & Bioscience Lab., Gifu, Japan
The aim of this study is to gain further insights into the possible nutraceutical effect on redox balance via thioredoxin (Trx) modulation and on the intrinsic susceptibility of monocytes to generate an inflammatory response. The study group consisted of thirty-two patients with compensated Child A-C, HCV-related cirrhosis. The patients were supplemented for 6 months with 6g/day of a certified fermented papaya preparation (FPP). Fifteen unsupplemented, age/gender-matched healthy subjects served as controls. The patients filled in a detailed diet-life style questionnaire, and blood samples were collected to test routine biochemistry, Trx, redox status (GSH, GSSG, GSH/GSSG ratio, 4-HNE and α-tocopherol). Moreover, isolated monocytes were tested for ex-vivo LPS-stimulated TNFα production and TNFα mRNA. As compared to control, patients with liver cirrhosis showed a significantly higher serum level of Trx. A significant correlation occurred with GSH/GSSG ratio in Child B and C patients.
FPP supplementation brought about a significant reduction of Trx with levels comparable to the ones of healthy controls. Ten patients Child C (31.2%) showed borderline low levels of α-tocopherol while all cirrhotic patients, as a whole, showed a significantly abnormal redox balance. Supplementation with FPP did not modify α-tocopherol depletion but significantly improved redox balance parameters.
Patients with liver cirrhosis showed a significantly upregulated TNF-α production in a time-dependent manner and this effect was more pronounced in more advanced stages of the disease and showed a significant correlation with α-tocopherol level. Supplementation with FPP significantly, although partially, downregulated TNF-α production from monocytes. Taken altogether, it would appear that the typical oxidative-inflammatory biochemical milieu of these patients is mirrored by a significant TNF-α upregulation at a monocyte level while a targeted nutraceutical might be a potentially amenable intervention to be part of validated scheduled treatments.
Ex-vivo LPS-stimulation test of TNF-α production from monocytes and PCR-electrophoresis: nutraceutical modulation. Data were obtained at 3 months observation. A) dotted bars: healthy control: black bars: unsupplemented cirrhotics; grey bars: FPP-supplemented cirrhotics. FPP: fermented papaya preparation. Stimulated monocytes from unsupplemented cirrhotic showed a significant time-course increase of TNFα production, * p< 0.01 vs healthy control. Nutraceutical supplementation partly but significantly decreased such phenomenon, ** p<0.05 vs unsupplemented cirrhotics. Top part of figure A shows the PCR electrophoresis of TNFα expression in LPS-stimulated cells from FPPsupplemented cirrhotic patients (TNFα + FPP) and in unsupplemented patients (TNFα). B) white bars: Child A; black bars: Child C, *p<0.05 vs Child A
Journal of Biological Regulator & Homeostatic Agents vol.24 no.2(2010)
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