Antinarcotic effects of the velvet antler water extract on morphine in mice.

The present study was undertaken to investigate the antinarcotic effects of velvet antler water extract (VAWE) from Cervus elaphus on morphine. Morphine-induced analgesic action was measured by tail-flick method. Morphine-induced hyperactivity and reverse tolerance were evidenced by measuring the enhanced ambulatory activity using a tilting-type ambulometer. Dopamine (DA) receptor supersensitivity in mice displaying morphine-induced reverse tolerance was evidenced by the enhanced response in ambulatory activity to the DA agonist, apomorphine. The repeated administration of VAWE significantly inhibits the development of morphine-induced analgesic tolerance, physical dependence, reverse tolerance and postsynaptic DA receptor supersensitivity. But a single administration of VAWE did neither antagonize morphine-induced analgesia nor inhibit morphine-induced hyperactivity. From the above results, it is presumed that VAWE may be useful for prevention and therapy of the adverse actions of morphine caused by the repeated administration of morphine.

The bisbenzylisoquinoline alkaloids, tetrandine and fangchinoline, enhance the cytotoxicity of multidrug resistance-related drugs via modulation of P-glycoprotein.

The occurrence of resistance to chemotherapeutic drugs is a major problem for successful cancer treatment and reducing drug accumulation by P-glycoprotein (P-gp) is one of the major mechanisms of multidrug resistance (MDR). The present study was performed to evaluate the MDR-reversal abilities of two bisbenzylisoquinoline alkaloids, tetrandine (TET) and fangchinoline (FAN), compared with verapamil (VER), a well-known P-gp modulator. TET (3.0 microM), FAN (3.0 microM) and VER (10.0 microM) reduced the paclitaxel (TAX) concentration required to achieve 50% inhibition of cell growth (EC50) to HCT15 (P-gp-positive) cells about 3100-, 1900- and 410-fold, and these compounds also reduced the EC50 value of actinomycin D (AMD) about 36.0-, 45.9- and 18.2-fold in the cells, respectively. Meanwhile, TET, FAN and VER had no effect on the cytotoxicity of the drugs to SK-OV-3 (P-gp-negative) cells. On the other hand, TET (3.0 microM), FAN (3.0 microM) and VER (10.0 microM) similarly enhanced the accumulation rates of rhodamine 123, a well known P-gp substrate, in HCT15 cells (200-250%). After efflux for 2 h with fresh medium, TET and FAN also enhanced the residual rate of rhodamine 123 about 5.0- and 2.6-fold in comparison with control, respectively. TET, FAN and VER could not affect the accumulation and residual rate of rhodamine 123 in SK-OV-3 cells. From the result, we conclude that TET and FAN enhanced the cytotoxicity of MDR-related drugs via modulation of P-gp.

Effects of ginseng total saponin on morphine-induced hyperactivity and conditioned place preference in mice.

A single or repeated administration of morphine in mice produced hyperactivity, conditioned place preference (CPP) and postsynaptic dopamine (DA) receptor supersensitivity. The hyperactivity induced by morphine was evidenced by measuring the enhanced ambulatory activity using a tilting-type ambulometer. CPP effects were evaluated assessing the increased time spent by the mice to morphine and the inhibition of CPP by the decreased time spent by the mice in the white compartment. Postsynaptic DA receptor supersensitivity in mice displaying a morphine-induced CPP was evidenced by the enhanced response in ambulatory activity to the DA agonist, apomorphine (2 mg/kg, s.c.). The intraperitoneal injection of ginseng total saponin (GTS) from the root of Panax ginseng C.A. Meyer (Araliaceae), prior to and during the morphine treatment in mice inhibited morphine-induced hyperactivity and CPP. GTS inhibited the development of postsynaptic DA receptor supersensitivity. A single dose administration of GTS also inhibited apomorphine-induced climbing behavior, showing the antidopaminergic action of GTS at the postsynaptic DA receptor. These results suggest that the development of morphine-induced CPP may be associated with the enhanced DA receptor sensitivity and that GTS inhibition of the morphine-induced hyperactivity and CPP may be closely related with the inhibition of dopaminergic activation induced by morphine.

Blockade by ginseng total saponin of methamphetamine-induced hyperactivity and conditioned place preference in mice.

Ginseng total saponin (GTS) inhibited methamphetamine-induced hyperactivity and conditioned place preference (CPP). Dopamine (DA) receptor supersensitivity was developed in methamphetamine-induced CPP mice and it was inhibited by GTS. GTS also inhibited apomorphine-induced climbing behavior, showing the antidopaminergic activity of GTS. These results suggest that GTS inhibition of the methamphetamine-induced hyperactivity and CPP may be closely related with the inhibition of dopaminergic activation induced by methamphetamine.

Microscopic localization of mercury-selenium interaction products in liver, kidney, lung and brain of Mediterranean striped dolphins (Stenella Coeruleoalba) by silver enhancement kit.

Microscopic observation, using physical development of silver, was carried out to localize the mercury-selenium interaction products in the organs of Mediterranean striped dolphins. The silver-metal reaction products were located mainly in hepatocytes and macrophages for liver, in proximal tubules for kidney. They were less abundant in lung than in liver and kidney. The result of semi-quantitative histochemistry tests showed that silver staining deposits were more abundant at relatively high metal concentrations than low metal contents, but independent of the metal contents. Comparisons with the most concentrated metal contents suggested that there might be a new complex of mercury and selenium, which could not be stainable by physical silver development.

Mercury, zinc and selenium bioaccumulation in tissues and organs of Mediterranean striped dolphins Stenella coeruleoalba meyen. Toxicological result of their interaction.

Neutron activation analysis of 13 Mediterranean striped dolphins Stenella coeruleoalba showed high mercury and selenium contaminations of main tissues and organs of these cetaceans. The mercuric contents were excessive, particularly in liver (from 68 to 2272 micrograms/g dry wt. basis), then in kidney, lung, muscle, heart and brain. The selenium concentrations were also high in liver (from 45 to 1320 micrograms/g dry wt. basis), then in kidney, lung, muscle, skin and heart. The main way of contamination seems to be the food through trophic network, but skin and lung are also able to play a part which must be elucidated. The average Hg/Se ratios in liver and kidney were respectively 1.82 and 1.59. Linear relationship between mercury and selenium concentrations in tissues and organs, particularly in liver and kidney, were confirmed. The mercury and selenium interaction on a toxicological point of view was established by a statistical approach; in the same way, intervention of zinc, metallothioneins and glutathiones have been discussed.