'Methyl palmitate attenuates adjuvant induced arthritis in rats by decrease of CD68 synovial macrophages

The study was designed to investigate the potential anti-arthritic effects of methyl palmitate in an adjuvant arthritis model in rats that shares many histopathological similarities with human RA. The underlying mechanism and its effect on CD68 macrophages were investigated, as a further argument to its possible efficacy in RA treatment. A normal control group was injected only with saline, arthritic group, and three treatment groups with CFA induced arthritis received methyl palmitate (MP) at three different doses (75, 150, 300 mg/kg/week for 3 weeks, intraperitoneal). The degree of ipsilateral paw swelling, ankle diameter, spleen index, thymus index and the expression levels of tumor necrosis factor (TNF)-α, interleukin (IL)-1β were measured. In addition, the underlying molecular mechanism was investigated using CD68 expression. Methyl palpitate significantly and dose dependently decreased the arthritic symptoms as measured by ipsilateral paw volume and ankle diameter. It showed no effect on body weight but significantly decreased splenic, thymus index, serum TNF-α and IL-1β. CD68 macrophages expression and the overall synovial inflammatory cellularity were halted. Methyl palmitate exhibits significant anti-inflammatory and exerts a potential anti-arthritic effect in a rat model of adjuvant induced arthritis. Furthermore, it inhibits expression of synovial CD68 macrophage that validate its therapeutic potential adjuvant arthritis

Thymoquinone blocks lung injury and fibrosis by attenuating bleomycin-induced oxidative stress and activation of nuclear factor Kappa-B in rats

Pulmonary fibrosis is one of the most common chronic interstitial lung diseases with high mortality rate after diagnosis and limited successful treatment. The present study was designed to assess the potential antifibrotic effect of thymoquinone (TQ) and whether TQ can attenuate the severity of oxidative stress and inflammatory response during bleomycin-induced pulmonary fibrosis. Male Wister rats were treated intraperitoneally with either bleomycin (15 mg/kg, 3 times a week for 4 weeks) and/or thymoquinone (5 mg/kg/day, 1 week before and until the end of the experiment). Bleomycin significantly increased lung weight and the levels of Lactate dehydrogenase, total leucocytic count, total protein and mucin in bronchoalveolar lavage and these effects were significantly ameliorated by TQ treatment. As markers of oxidative stress, bleomycin caused a significant increase in the levels of lipid peroxides and nitric oxide accompanied with a significant decrease in the antioxidant enzyme activity of superoxide dismutase and glutathione transferase. TQ treatment restored these markers toward normal values. TQ also coun- teracted emphysema in air alveoli, inflammatory cell infiltration, lymphoid hyperplastic cells activation surrounding the bronchioles and the over expression of activated form of nuclear factor kappa-B (NF-B) in lung tissue that was induced by bleomycin. Fibrosis was assessed by measuring hydroxyproline content, which increased markedly in the bleomycin group and significantly reduced by concurrent treatment with TQ. Furthermore, histopathological examination confirmed the antifibrotic effect of TQ. Collectively these findings indicate that TQ has potential antifibrotic effect beside its antioxidant activity that could be through NF- B inhibition

Effect of bee venom on pharmacokinetic parameters and constants of a single dose of methotrexate.

<p>-Data is represented as means ± SD (n = 15), normal rats injected with single dose of methotrexate (Single MTX), normal rats injected with bee venom for 3 weeks followed by single dose of methotrexate (Single MTX+BV),</p>*<p>means significantly different from the corresponding (single MTX) group at P<0.05 using unpaired student's t-test.</p

Bee venom effect on plasma concentrations, synovial fluid and tissue concentrations of methotrexate single dose.

<p>Panel A: plasma concentrations of methotrexate, panel B: different tissue concentrations of methotrexate. Data are represented as mean ± SD or percentage change of MTX group (n = 15).* means significantly different from the corresponding MTX group at P<0.05 using unpaired student's t-test.</p

Methotrexate and/or BV effect on Tissue necrosis factor-alpha expression in synovial membrane of hind paw.

<p>Immunohistochemical staining (×100) of paw sections of A: normal rat shows almost negative immunostaining for TNF-α, B: arthritic non-treated rat shows massive immunostaining, C: MTX treated rat shows moderate immunostaining, D: BV treated rat shows mild immunostaining and E: concurrently treated rat with MTX and BV shows minimal TNF-α expression. F: mean optical density of synovial membrane stained with TNF-α immunostaining in different studied groups. Data are represented as mean ± SD (n = 10). a, b, c or d: significantly different from the corresponding Normal, Arth, MTX or BV group respectively at P<0.05 using one-way ANOVA followed by Tukey-Kramer Multiple comparison test.</p

Effect of methotrexate and/or BV on ankle diameter, paw volume and paw withdrawal latency.

<p>Panel A: percentage change in ankle diameter, panel B: paw volume changes and panel C: percentage inhibition of paw withdrawal latency (PWL) from pre-injection values in adjuvant induced arthritic rats over a period of 21 days. Data are represented as mean ± SD. a or b: significantly different from the corresponding Arth or MTX group, respectively at P<0.05 using repeated measures of ANOVA followed by Tukey-Kramer Multiple Comparison Test.</p

Photomicrographs of liver sections stained by H & E (×400).

<p>A: liver section of normal rat shows normal central vein (CV) and surrounding hepatocytes (h). B: liver section of arthritic non-treated rat shows degeneration in hepatocytes (d). C and D: liver sections of arthritic rat treated with MTX alone shows severe fatty change (f), degeneration (d) of hepatocytes, congested portal tract (PT) and lost cell boundaries with distortion of normal architecture (circle). E: liver section of arthritic rat treated with BV alone shows normal hepatic architecture. F: liver section of arthritic rat concurrently treated with MTX and BV showing mild congestion in the central vein (CV) with diffuse kupffer cells proliferation (arrow) in between hepatocytes.</p

Methotrexate and/or BV effect on NF-κB (p65) expression in liver.

<p>Immunohistochemical staining (×400) of liver sections of A: normal rat shows almost negative immunostaining, B: arthritic non-treated rat shows moderate immunostaining, C: MTX treated rat shows intense immunostaining, D: BV treated rat shows mild immunostaining and E: concurrently treated rat with MTX and BV shows minimal NF-κB p65 expression. F: mean optical density of liver tissue sections immunostained with NF-κB p65 in different studied groups. Data are represented as mean ± SD (n = 10). a, b, c or d: significantly different from the corresponding Normal, Arth, MTX or BV group respectively at P<0.05 using one-way ANOVA followed by Tukey-Kramer Multiple comparison test.</p