Q96246727
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Rheumatoid arthritis (RA) and its animal model adjuvant arthritis (AA) are inflammatory diseases characterized by chronic inflammation, systemic oxidative stress and disturbed mitochondrial bioenergetics of skeletal muscle. The present study aimed to evaluate the effects of coenzyme Q10 - CoQ10 (100 mg/kg b.w.), omega-3-polyunsaturated fatty acids - omega-3-PUFA (400 mg/kg b.w.) and their combined treatment in AA on impaired skeletal muscle mitochondrial bioenergetics, inflammation and changes in levels CoQ9 and CoQ10 in plasma. Markers of inflammation (C-reactive protein, monocyte-chemotactic protein-1), antioxidant capacity of plasma, respiratory chain parameters of skeletal muscle mitochondria and concentrations of CoQ9 and CoQ10 in plasma and in muscle tissue were estimated. Treatment of the arthritic rats with CoQ10, omega-3-PUFA alone and in combination partially reduced markers of inflammation and increased antioxidant capacity of plasma, significantly increased concentrations of coenzyme Q in mitochondria and improved mitochondrial function in the skeletal muscle. Combined treatment has similar effect on the mitochondrial function as monotherapies; however, it has affected inflammation and antioxidant status more intensively than monotherapies. Long-term supplementary administration of coenzyme Q10 and omega-3-PUFA and especially their combination is able to restore the impaired mitochondrial bioenergetics and antioxidant status in AA.
- MeSH
- antioxidancia metabolismus MeSH
- artritida experimentální krev dietoterapie MeSH
- C-reaktivní protein metabolismus MeSH
- chemokin CCL2 krev MeSH
- omega-3 mastné kyseliny terapeutické užití MeSH
- potkani inbrední LEW MeSH
- potravní doplňky MeSH
- revmatoidní artritida krev dietoterapie MeSH
- svalové mitochondrie metabolismus MeSH
- ubichinon analogy a deriváty metabolismus terapeutické užití MeSH
- zvířata MeSH
- Check Tag
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- hodnotící studie MeSH
Salidroside, as a chemical compound from the group of phenylpropanoids, and rosavin are used for the standardization of dry extracts from the underground stem and root of Rhodiola rosea. In this study we monitored two different extracts from Rhodiola rosea, which differ in content of active compounds, colour, technological and physico-chemical properties (e.g. flow properties). These extracts were mixed with excipients and the flow characteristics of mixture – bulk volume and tapped volume – were determined. After formulating the tablets by compression, qualitative parameters like disintegration, resistance to crushing, friability, mass uniformity and texturometric parameters were tested. Also, dissolution profiles were evaluated using first order kinetic model, Korsmeyer-Peppas model and Weibull model for correlation. In some formulations, the impact of the properties of dry extracts on various technological properties of final tablets was more marked. We suggest that in case of a higher extract:excipients ratio, these properties manifest themselves by an even higher impact.
In this study, two extracts from Fatsia japonica-FatsiphloginumTM (extract of triterpene glycosides containing 45-50 % of fatsiosides (FS)) and purified triterpene-rich extract of saponins with code name PS-551 (PS) were administered in combination with methotrexate (MTX) and in monotherapy to rats suffering adjuvant arthritis (AA). The anti-inflammatory activities of extracts were evaluated as monotherapies in comparison with untreated AA. PS administered in higher dose showed on day 28 effective decrease of hind paw volume (HPV), decreased activity of gamma-glutamyl transferase (GGT) in joints, and also interleukin-17A was decreased significantly on day 14. The higher dose of PS was more effective than both doses of FS. Further, we evaluated the higher doses of PS and FS in combination with MTX. PS improved the effect of MTX in combination more effective than FS (HPV, body weight and activity of GGT in joint). However, FS was more effective in reducing the level of IL-17A on day 14 and activity of GGT in spleen than PS. In conclusion, our study showed that generally FS has higher anti-arthritic activity comparing to PS. Thus, the novel combination of FatsiphloginumTM and methotrexate could be interesting for future clinical studies in patients suffering auto-immune diseases.
- MeSH
- antiflogistika aplikace a dávkování MeSH
- aralkovité chemie MeSH
- artritida experimentální farmakoterapie MeSH
- gama-glutamyltransferasa metabolismus MeSH
- interleukin-17 krev MeSH
- krysa rodu rattus MeSH
- methotrexát aplikace a dávkování MeSH
- potkani inbrední LEW MeSH
- rostlinné extrakty terapeutické užití MeSH
- saponiny aplikace a dávkování MeSH
- triterpeny aplikace a dávkování MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
Rheumatoid arthritis (RA) is a chronic inflammatory disease, leading to progressive destruction of joints and extra-articular tissues, including organs such as liver and spleen. The purpose of this study was to compare the effects of a potential immunomodulator, natural polyphenol N-feruloylserotonin (N-f-5HT), with methotrexate (MTX), the standard in RA therapy, in the chronic phase of adjuvant-induced arthritis (AA) in male Lewis rats. The experiment included healthy controls (CO), arthritic animals (AA), AA given N-f-5HT (AA-N-f-5HT), and AA given MTX (AA-MTX). N-f-5HT did not affect the body weight change and clinical parameters until the 14th experimental day. Its positive effect was rising during the 28-day experiment, indicating a delayed onset of N-f-5HT action. Administration of either N-f-5HT or MTX caused reduction of inflammation measured as the level of CRP in plasma and the activity of LOX in the liver. mRNA transcription of TNF-α and iNOS in the liver was significantly attenuated in both MTX and N-f-5HT treated groups of arthritic rats. Interestingly, in contrast to MTX, N-f-5HT significantly lowered the level of IL-1β in plasma and IL-1β mRNA expression in the liver and spleen of arthritic rats. This speaks for future investigations of N-f-5HT as an agent in the treatment of RA in combination therapy with MTX.
- MeSH
- arachidonátlipoxygenasy genetika metabolismus MeSH
- artritida experimentální farmakoterapie genetika patologie MeSH
- biologické markery MeSH
- C-reaktivní protein MeSH
- časové faktory MeSH
- cytokiny krev genetika metabolismus MeSH
- játra účinky léků metabolismus MeSH
- krysa rodu rattus MeSH
- mediátory zánětu * MeSH
- methotrexát farmakologie MeSH
- modely nemocí na zvířatech MeSH
- orgánová specificita MeSH
- regulace genové exprese účinky léků MeSH
- serotonin analogy a deriváty farmakologie MeSH
- stupeň závažnosti nemoci MeSH
- transkriptom * MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
Carnosine (CARN) is an anti-glycating agent able to quench superoxide, and to neutralize 4-hydroxynonenal. Trolox-carnosine (CARN-T) was synthesized because of its resistance against degradation and to improve CARN antioxidant capacity. We evaluated the impact of trolox (TRO), CARN and its derivative CARN-T on oxidative stress (OS) in brain during rat adjuvant arthritis (AA). The experiments were done on healthy, control arthritic and arthritic animals with administration of CARN 150 mg/kg b.w., TRO 41 mg/kg b.w. and CARN-T 75 mg/kg b.w. in a daily dose during 28 days. Antioxidants did not affect the body weight on day 14, but on day 28 TRO enhanced the weight reduction. On day 14 and 28 CARN-T and TRO reduced arthritic score. IL-1beta, MCP-1 and MMP-9 were measured in plasma on day 14. MCP-1 was decreased by CARN-T and TRO. All antioxidants reduced IL-1beta and MMP-9 levels. Malondialdehyde, 4-hydroxynonenal and protein carbonyls were increased in brain. CARN, CARN-T and TRO prevented higher lipid and protein oxidation in brain. CARN and CARN-T caused no weight reduction like TRO that has an advantage in inflammatory arthritis. Moreover the antioxidants administered had a similar therapeutic effects on arthritic score, markers of inflammation in plasma and OS in brain.
- MeSH
- antioxidancia farmakologie terapeutické užití MeSH
- artritida experimentální farmakoterapie metabolismus MeSH
- chromany (dihydrobenzopyrany) farmakologie terapeutické užití MeSH
- karnosin analogy a deriváty farmakologie terapeutické užití MeSH
- krysa rodu rattus MeSH
- mozek účinky léků metabolismus MeSH
- oxidační stres účinky léků fyziologie MeSH
- potkani inbrední LEW MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
There is evidence that a higher serum level of bilirubin (BIL) may be a protective factor for autoimmune diseases. We examined the effect of BIL supplementation in adjuvant-induced arthritis (AIA) where oxidative stress, inflammation and inadequate immune response are present. Male Lewis rats were randomized into groups: CO - control, AIA - untreated adjuvant-induced arthritis, AIA-BIL - adjuvant-induced arthritis administrated BIL (200 mg/kg b.w. daily i.p. during 14 days). Change of hind paw volume in the AIA-BIL group in comparison to the AIA group was significantly decreased after BIL administration. In CO and AIA groups we found almost untraceable levels of BIL. In the AIA-BIL group hyperbilirubinemia was observed. BIL administration significantly decreased plasma levels of C-reactive protein and ceruloplasmin in the AIA-BIL group in comparison to the AIA group. The values of white and red blood cells, hemoglobin and hematocrit were significantly decreased in AIA-BIL after BIL supplementation. Organs like spleen and thymus had a lower weight in AIA-BIL than in AIA. Histological findings showed decreased or even absent damage in hind paw joint of AIA-BIL animals. We observed an immunomodulatory effect of BIL on AIA development, which may also have a novel pharmacological impact.
- MeSH
- artritida experimentální krev patologie MeSH
- bilirubin krev MeSH
- biologické markery krev MeSH
- hyperbilirubinemie krev patologie MeSH
- krysa rodu rattus MeSH
- potkani inbrední LEW MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
It has been demonstrated that pterostilbene inhibits reactive oxygen species production in neutrophils in vitro. However, little is known about its effects on neutrophils during inflammation in vivo. In this study, the effect of pterostilbene on neutrophil activity was investigated in experimental arthritis model. Lewis rats were injected by a single intradermal injection of heat-killed Mycobacterium butyricum in Freund's adjuvant to develop arthritis. Another group of arthritic animals received pterostilbene 30 mg/kg, daily, p.o. The number and activity of neutrophils in blood were measured on a weekly basis during the whole experiment. Moreover, the total radical trapping potential in plasma was measured at the end of the experiment. In the pterostilbene treated arthritic group, the treatment significantly lowered the number of neutrophils in blood on days 14 and 21 without significant downregulation of neutrophil oxidative burst. Pterostilbene nonsignificantly increased total radical trapping potential in arthritic animals. These results indicate that the promising effects of pterostilbene on reactive oxygen species operate by different mechanisms in vitro and in the animal model of inflammation. In conclusion, the positive effects of pterostilbene in the model of arthritis may be attributed to regulation of neutrophil number.
- MeSH
- artritida experimentální farmakoterapie patologie MeSH
- down regulace účinky léků MeSH
- krysa rodu rattus MeSH
- modely nemocí na zvířatech MeSH
- nepřímá aktivace účinky léků imunologie MeSH
- neutrofily cytologie účinky léků patologie MeSH
- peroxidy metabolismus MeSH
- počet leukocytů MeSH
- potkani inbrední LEW MeSH
- reaktivní formy kyslíku metabolismus MeSH
- stilbeny chemie farmakologie terapeutické užití MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
