S. Das Gupta

Effect of topically applied sulphur mustard on antioxidant enzymes in blood cells and body tissues of rats

The effect of sulphur mustard (0.5 LD50, percutaneous) on antioxidant enzymes (superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GSH‐Px)) in blood cells (erythrocytes (RBC), leucocytes (WBC) and platelets) and body tissues (liver, kidney, spleen and brain) of rats has been investigated 24 h post exposure. The SOD activity was significantly decreased in WBC, platelets, spleen and brain as compared to control. The CAT activity was significantly inhibited in RBC, WBC and spleen as compared to control. The GSH‐Px activity was significantly depressed in WBC, spleen and liver as compared to control. It is concluded that sulphur mustard at a sublethal dose inhibited antioxidant enzyme activities in WBC and spleen. Thus, antioxidant enzymes in lymphatic tissues may be used as suitable models for assessing mustard toxicity. The study suggests the formation of reactive oxygen species in sulphur mustard intoxication.

Combined exposure to lead and ethanol on tissue concentration of essential metals and some biochemical indices in rat

The effect of daily oral administration of ethanol (2.5, 5, or 10% in drinking water for 8 wk), lead (10 mg/kg, po, once daily for 8 wk), or their combination on tissue trace-metal concentration and hematopoietic and hepatic biochemical indices was investigated in male rats. Ethanol (10%) ingestion enhanced the hepatic lipid peroxidation and decreased the calcium and magnesium content of blood and liver. Coexposure to lead and ethanol (5 and 10%) produced a more pronounced elevation of blood zinc protoporphyrin (ZPP) and hepatic lipid peroxidation. Combined lead-ethanol exposure also lowered the concentration of blood and hepatic magnesium and calcium and increased the amount of lead in the blood, liver, and brain compared to a group treated with lead alone. The results suggest that chronic alcohol ingestion results in calcium and magnesium loss. However, coexposure to lead and ethanol could result in more serious depletion of calcium and magnesium, and this could be the cause of suspected synergism between alcohol consumption and lead poisoning.

Mobilization and Distribution of Beryllium Over the Course of Chelation Therapy with Some Polyaminocarboxylic Acids in the Rat

The efficacy of three common polyaminocarboxylic acids in the treatment of experimental beryllium intoxication was investigated in male rats. N-(2-hydroxyethyl) ethylene diamine triacetic acid (HEDTA) was more effective than calcium disodium ethylenediamine tetraacetic acid (CaNa2EDTA) in reducing the beryllium concentration of the blood, kidneys and spleen and reducing beryllium-induced inhibition of hepatic alkaline phosphatase activity. HEDTA was also most effective in reducing histopathological lesions in the liver and spleen. Compared to these two chelators, the third amino chelator, calcium trisodium diethylene triaminepenta acetic acid (CaNa3DTPA) produced severe deleterious effects in the liver and systemic toxicity. The results suggest that HEDTA is a promising chelator for beryllium toxicity while DTPA enhances the toxic manifestation of beryllium.

Protection against cyanide poisoning by the co-administration of sodium nitrite and hydroxylamine in rats.

1 The protectiveness of combined treatment with sodium nitrite (SN) and hydroxylamine (HA) in cyanide intoxication was investigated in male rats. 2 Pretreatment with equimolar dose of SN or HA produced a significant protection against cyanide poisoning as shown by the protection index (LD50 of cyanide in protected rats/LD50 of cyanide in saline-treated rats). 3 The co-administration of SN and HA as a split dose produced an optimal and sustained methaemoglobinaemia. 4 Pretreatment with combined SN and HA administration at different time intervals offered sustained protection against cyanide and resultant cytochrome oxidase inhibition. 5 Adjunction of sodium thiosulphate (STS) in the SN + HA regimen further augmented the protection against cyanide poisoning. 6 The results suggest that pretreatment with SN + HA co-administration could significantly reduce the toxic manifestation of cyanide.

Relative potency of synthetic analogs of Ptychodiscus brevis toxin in depressing synaptic transmission evoked in neonatal rat spinal cord in vitro.

Effects of Ptychodiscus brevis toxin (PbTx) analogs on the spinal synaptic transmission in neonatal rats in vitro were evaluated. PbTx1/PbTx2 had aromatic groups and PbTx3/PbTx4 had aliphatic groups. All the analogs depressed monosynaptic reflex (MSR) and polysynaptic reflex (PSR) in a concentration-dependent manner. The maximal depression of MSR (75% from initial) and PSR (96%) was at 84 microM for PbTx1. Concentration to produce 25% inhibition from initial (IC25) by PbTx1 for MSR and PSR was < or =2.8 microM. The maximal depression of MSR (80%) was at 96 microM and PSR (100%) was at 32 microM by PbTx2. IC25 for MSR and PSR were 5.5 microM and <3.2 microM, respectively. PbTx3 decreased MSR by 25% maximally (=IC25) at 36 microM. The depression of PSR fluctuated and was maximal (75%) at 108 microM and IC25 was 6.2 microM. PbTx4 depressed MSR and PSR at the maximum of 35% at 32 microM and IC25 for MSR was 8.3 microM and for PSR was 35 microM. Rank order of potency of toxins for depressing MSR was PbTx1>PbTx2>>PbTx4>PbTx3; and for PSR it was PbTx2>PbTx1>PbTx3>>PbTx4. Results indicate that the toxins having aromatic groups exhibited greater neurotoxicity.

Actions and Interactions of Cholinolytics and Cholinesterase Reactivators in the Treatment of Acute Organophosphorus Toxicity

Different drug combinations consisting of cholinolytic and a cholinesterase (ChE) reactivator provide greater therapeutic efficacy in acute organophosphorus (OP) poisoning in mice than when used alone. Maximum protection, as determined by a shift of the LD50 for the two OP agents, was observed with the cholinolytic benactyzine. A protection index (P.I.) of 42 was obtained when benactyzine was given along with obidoxime in diisopropylphosphorofluoridate (DFP) intoxication. With the more toxic OP agent soman (o-pinacolylmethylphosphonofluoridate), the same cholinolytic only offered a maximum P.I. of 3.2 when administered with HS-6, another bispyridinium ChE reactivator. This beneficial effect of benactyzine is possibly due to its greater antimuscarinic effect in the central nervous system than atropine or dexetimide.

Cyanide Antagonism in a Rodent Model

The prophylactic experimental approach to counter cyanide poisoning involves pretreatment with methemoglobin producers viz. sodium nitrite (NaNO2) and aminophenols (Kiese and Weger 1965). 4-Dimethylaminophenol (DMAP), a rapid methemoglobin former was suggested to give greater protection than nitrite (Kiese and Weger 1969). However, its clinical application is limited because of its toxicity (Szinicz et al 1979) and inability to offer a sustained protection for longer duration, when personnel are at risk to cyanide exposure while negotiating an industrial disaster. A protracted methemoglobinemia is presumed to offer sustained protection against cyanide poisoning. Hence, in the present study, the efficacy of sustained methemoglobinemia was studied in rats as a result of co-administration of NaNO2 (slow methemoglobin producer) and DMAP in appropriate doses. A reduction in DMAP dosages is also envisaged based on methemoglobin kinetics.

Effect of thiamine hydrochloride on the blood level of 2-formyl 1-methyl pyridinium oxime chloride (2-PAM.Cl) in rats

The biological half-life of 2-PAM.Cl was found to increase in female rats pretreated with thiamine hydrochloride (10 mg/kg i.m.). No such effect was observed in the male rats.

Studies on urine and tissues of rats, guineapigs and mice exposed to sulphur mustard using mass spectrometry

Urine and tissues (brain, liver, kidney, fat and triceps muscles) from rodents (rats, guinea pigs and albino mice) treated with sulphur mustard percutaneously were examined for the presence of sulphur mustard and/or metobolites using electron impact direct inlet and GC-mass spectrometry. Sulphur mustard and thiodiglycol sulphoxide were not detected in these samples even after application of massive doses. However, thiodiglycol was identified in urine only

Diisopropylphosphorofluoridate-induced depression of compound action potential of frog sciatic nerve in vitro is mediated through the inhibition of cholinesterase activity

Effect of diisopropylphosphorofluoridate (DFP), an irreversible cholinesterase (ChE) inhibitor, on compound action potential (CAP) of sciatic nerve in vitro was examined. Further, the role of cholinesterase reactivator (1 acetyl‐4‐hydroxy imino methyl pyridinium bromide; SPK‐3) in reversing DFP‐induced changes was also evaluated. Diisopropylphosphorofluoridate produced a dose‐dependent depression of the CAP. A concentration as low as 0.01 μM DFP produced a 5% depression (P < 0.05) and the maximal depression (30% of control) was observed with 1 μM. The SPK‐3 (up to 10 μM) had no effect on the CAP; SPK‐3 (10 μM) antagonized the DFP‐induced depression of the CAP partially but not after 1 μM DFP. However, the inhibitory concentration of DFP to produce 50% of the maximal depression (ic50) was 0.38 ± 0.025 μM in the presence of SPK‐3 (10 μM; n = 4), against 0.15 ± 0.05 μM for DFP alone (n = 7).These ic50 values were significantly different (P < 0.05, Students t‐test). The DFP decreased nerve ChE activity by 41% in t he absence of SPK‐3 and by 31% in the presence of SPK‐3. Although SPK‐3 could not completely reactivate the inhibited enzyme, it seems reasonable to conclude that the DFP‐induced depression of the action potential of sciatic nerve was mediated by inhibiting the ChE activity.