New Zealand green-lipped mussel Verna canaliculus possesses an anti-inflammatory activity in the rat adjuvant arthritis with no ulcerogenic effect: the role of cytokines and antioxidant mechanisms

ABSTRACT

This study investigated the possible prophylactic and therapeutic anti-inflammatory effect of New Zealand green-lipped mussel [NZGLM] in adjuvant arthritis [AA] as well as its probable ulcerogenic activity in comparison with other NSAIDs used in arthritic disorders and the likely mechanisms underlying these potential effects. Arthritis was induced by s.c. injection of Freund's complete adjuvant into the right hind paw of Wistar rats of all groups except the normal one. The adjuvant was injected in one of the footpads to allow study of the acute inflammatory reaction in that local area of the injected paw as well as the immunological reaction that develops approximately 9 days later in the contralateral paw. Treatments with diclofenac [2 mg/kg/po] and NZGLM [250, 1000 mg/kg/po] were initiated on day 0, which is the day of adjuvant injection [prophylactic model dosing] or day 9 [therapeutic model] and continued once daily till day 21. The normal group and a control arthritic group were given oral 1% Tween 80. Both the injected and the contralateral paws' volumes were measured before adjuvant inoculation and then every 2-3 days by volume displacement. After the last measurement, blood samples were collected and were used for serum determination of tumor necrosis factor-a [TNF-alpha], interleukin-1 p [IL-1[3], malondialdehyde and nitrite. In the ulcerogenicity study, rats were injected with the adjuvant in the hind paw and at day 16 post-induction, the A A rats were then divided into 3 groups, 2 groups were treated daily for 5 days with indomethacin [3 mg/kg/po] or NZGLM [1000 mg/kg/po], while the 3rd group served as control. The animals were fasted for 20 hrs on day 4 prior to the final dose and then sacrificed 4 hrs after the, final dose of drug and their stomachs were removed, and examined for the total lesion score. Gastric mucosal homogenates were used for the estimation of lipid peroxides and myeloperoxidase activity. NZGLM exerted a significant dose-dependent anti-inflammatory effect in the AA model, its higher dose being comparable to that of diclofenac and that this effect is likely to be mediated by inhibiting the proinflammatory cytokines; TNF-alpha and IL-lp and through its antioxidant properties. In contrast to indomethacin, NZGLM did not produce any significant ulcerogenic effect