Protective effect of ethanolic and water extracts of sea buckthorn (Hippophae rhamnoides L.) against the toxic effects of mustard gas.

Ethanolic extract of H. rhamnoides L. leaf (HL-EOH), water and ethanolic extract of H. rhamnoides fruit (HF-W and HF-EOH), and H. rhamnoides flavone from fruit (HR-flavone) were evaluated against percutaneously administered sulphur mustard (SM), a chemical warfare agent. The animals administered with SM (9.7, 19.3 and 38.7 mg/kg) died at various days depending upon the dose and there was a significant reduction in the body weight. The H. rhamnoides extracts (1 g/kg; 3 doses; po) significantly protected the lethality, with a protective index of 2.4, 1.7, 1.7 and 2.2 for HL-EOH, HF-W, HF-EOH and HR-flavone respectively. Reduced glutathione (GSH) and oxidized glutalthione (GSSG) levels were reduced, and malondialdehyde (MDA) was elevated after percutaneous administration of SM. Oral administration of HL-EOH and HR-flavone significantly protected the body weight loss. Recovery in the levels of GSH, GSSG and MDA were also observed following oral administration of HL-EOH and HR-flavone. All the extracts were non-toxic and the LD50 was more than 5 g/kg. The present study shows that percutaneous administration of SM induces oxidative stress and ethanolic extract of leaf of H. rhamnoides and H. rhamnoides flavone from fruit can significantly protect it.

Mechanism of cardiotoxicity induced by a marine toxin isolated from Ptychodiscus brevis.

An organophosphate toxin of marine origin isolated from red tide dinoflagellate P. brevis produced a dose-dependent dual effect on rat atria, i.e. positive inotropic effect at low concentrations (2.8 x 10(-8) to 8.4 x 10(-7) M) and negative inotropic and chronotropic responses at an elevated dose (4.8 x 10(-6) to 7.2 x 10(-4) M). The negative chronotropic and inotropic responses of the toxin were potentiated with physostigmine and ouabain whereas antagonized by atropine and hemicholinium-3 pretreatments and those effects remained unaltered by isoproterenol, phenylephrine and ouabain pretreatments. The results indicate that the toxin induced negative inotropic and chronotropic effects are mediated through release of acetylcholine from the nerve endings and consequent activation of muscarinic receptor. In atria exposed to guanethidine, bretylium, propranolol and tyramine tachyphylaxis, the positive inotropic response of the toxin was not modified. However, the response was antagonized by EGTA, nifedipine, ryanodine, calcium-free ringer and potentiated with caffeine and amiloride pretreatments. The results suggest that the positive inotropic effect of the toxin is mediated through Ca2+ influx and impairment of Na+/Ca2+ exchange process.