Role of nigella sativa oil, thymoquinone with and without pyrimethamine in freund's adjuvant arthritis in rat

ABSTRACT

Nigella sativa oil and its active principal thymoquinone have been screened for their beneficialeffects that had been attributed to their cytoprotective, antioxidant actions and to their effect on many mediators ofinflammation. Similarly, pyrimethamine [PY], which is well known for its anti-parasitic action for a long time, hasbeen reported to have immunomodulating and apoptotic activities. The aim of the present study was to investigate the effect of Nigella sativa oil [NSO] andthymoquinone [TQ] in Freund's adjuvant arthritis [AA] in rats, an immunological experimental model of arthritiseither by sole administration of each of them or by their combination with pyrimethamine. The pain response and polyarthritis index were scored. Certain biochemical markers of inflammation,namely, interleukin-6 [IL-6], leukotriene B[4][LTB[4]], Matrix metalloproteinase-9 [MMP-9] were measured.Oxidative stress indices; reduced glutathione [GSH], erythrocytic superoxide dismutase [SOD] activity andmalondialdehyde [MDA] were also assayed in the sera of studied rats. The study demonstrated secondary inflammatory reactions in adjuvant arthritic rats [AA] as compared tothe control non- arthritic group. The study also revealed significant suppression of these secondary inflammatoryreactions as guided by reduction in the mean values of both polyarthritis index and pain response score in AA-treated rats. Significant reduction in IL-6, LTB[4], MMP-9 in the serum of treated groups was observed. This wasaccompanied with a significant increase in GSH serum level together with reduction of MDA levels in the treatedgroups. SOD activity did not change with the observed protection obtained by the studied drugs. PY + TQ, then PY + NSO, TQ and lastly NSO had reduced secondary reaction to Freund's adjuvantinoculation when used in the day of inoculation up to 20 days. It can be also concluded that combination with PYenhanced the chemoprotective effects of both TQ and NSO. Further experimental and clinical trials have to bedone for further screening of such combinations