Behavioral toxicity of sodium cyanide following oral ingestion in rats: Dose-dependent onset, severity, survival, and recovery.

Sodium cyanide (NaCN) is a commonly and widely used industrial and laboratory chemical reagent that is highly toxic. Its availability and rapid harmful/lethal effects combine to make cyanide a potential foodborne/waterborne intentional-poisoning hazard. Thus, laboratory studies are needed to understand the dose-dependent progression of toxicity/lethality following ingestion of cyanide-poisoned foods/liquids. We developed an oral-dosing method in which a standard pipette was used to dispense a sodium cyanide solution into the cheek, and the rat then swallowed the solution. Following poisoning (4-128 mg/kg), overt toxic signs were recorded and survival was evaluated periodically up to 30 hours thereafter. Toxic signs for NaCN doses higher than 16 mg/kg progressed quickly from head burial and mastication, to lethargy, convulsions, gasping/respiratory distress, and death. In a follow-on study, trained operant-behavioral performance was assessed immediately following cyanide exposure (4-64 mg/kg) continuously for 5 h and again the following day. Onset of behavioral intoxication (i.e., behavioral suppression) occurred more rapidly and lasted longer as the NaCN dose increased. This oral-consumption method with concomitant operantbehavioral assessment allowed for accurate dosing and quantification of intoxication onset, severity, and recovery, and will also be valuable in characterizing similar outcomes following varying medical countermeasure drugs and doses.

In vivo studies on hepato-renal impairments in freshwater fish Cyprinus carpio following exposure to sublethal concentrations of sodium cyanide.

Reactive oxygen species is an inevitable composite of aerobic systems that could channelize their lethality by imparting oxidative stress under a stressful environment. Cyanide is an important environmental toxicant that could be responsible in the resulting detrimental health issues of aquatic fauna. The present effort investigates the possibilities of hepato-renal damage in freshwater fish Cyprinus carpio following exposure to sublethal concentrations of sodium cyanide (NaCN). Fish were exposed to 0.1 mg/L of NaCN for 10 days (E1) and 20 days (E2) and were further subjected to recovery for 14 days (R) in NaCN-free medium. Liver tissue exhibited a significant decline in activity of catalase, superoxide dismutase, glutathione peroxidase, and glutathione S-transferase enzymes in exposed fish, unlike in control (C). Subsequent levels of lipid peroxidation elevation at 'E1' and 'E2' suggested oxidative damage to hepatocytes. This was further confirmed through a histopathological evaluation which indicated important findings like lymphocytic infiltration and necrosis in liver and tubular and glomerular degeneration in renal organ. The investigation suggests biochemical and histopathological alterations in fish following exposure to NaCN. Nevertheless, fish upon the recovery period were known to exhibit incomplete recuperation which was indicated by partial restoration tendencies under biochemical and histopathological factions. The study clearly implicated the role of NaCN in emphasizing its toxicity to C. carpio, further suggesting lack of recovery transition at a limited tenure of 14 days. The study might contribute in the course of regulatory surveillance and monitoring of aquatic bodies and may also reflect the possibilities of NaCN contamination during aquaculture practices. Graphical Abstract ᅟ.

Sodium cyanide induced alteration in the whole animal oxygen consumption and behavioural pattern of freshwater fish Labeo rohita.

Sodium cyanide is a common environmental pollutant which is mainly used in many industries such as mining, electroplating, steel manufacturing, pharmaceutical production and other specialized applications including dyes and agricultural products. It enters aquatic environment through effluents from these industries. Static renewal bioassay test has been conducted to determine LC, of sodium cyanide on indigenous freshwater carp, Labeo rohita. The behavioural pattern and oxygen consumption were observed in fish at both lethal and sub lethal concentrations. Labeo rohita in toxic media exhibited irregular and erratic swimming movements, hyper excitability, loss of equilibrium and shrinking to the bottom, which may be due to inhibition of cytochrome C oxidase activity and decreased blood pH. The combination of cytotoxic hypoxia with lactate acidosis depresses the central nervous system resulting in respiratory arrest and death. Decrease in oxygen consumption was observed at both lethal and sub lethal concentrations of sodium cyanide. Mortality was insignificant at sub lethal concentration test when fishes were found under stress. Consequence of impaired oxidative metabolism and elevated physiological response by fish against sodium cyanide stress showed alteration in respiratory rate.

Noninvasive optical cytochrome c oxidase redox state measurements using diffuse optical spectroscopy.

A major need exists for methods to assess organ oxidative metabolic states in vivo. By contrasting the responses to cyanide (CN) poisoning versus hemorrhage in animal models, we demonstrate that diffuse optical spectroscopy (DOS) can detect cytochrome c oxidase (CcO) redox states. Intermittent decreases in inspired O2 from 100% to 21% were applied before, during, and after CN poisoning, hemorrhage, and resuscitation in rabbits. Continuous DOS measurements of total hemoglobin, oxyhemoglobin, deoxyhemoglobin, and oxidized and reduced CcO from muscle were obtained. Rabbit hemorrhage was accomplished with stepwise removal of blood, followed by blood resuscitation. CN treated rabbits received 0.166 mg/min NaCN infusion. During hemorrhage, CcO redox state became reduced concurrently with decreases in oxyhemoglobin, resulting from reduced tissue oxygen delivery and hypoxia. In contrast, during CN infusion, CcO redox state decreased while oxyhemoglobin concentration increased due to CN binding and reduction of CcO with resultant inhibition of the electron transport chain. Spectral absorption similarities between hemoglobin and CcO make noninvasive spectroscopic distinction of CcO redox states difficult. By contrasting physiological perturbations of CN poisoning versus hemorrhage, we demonstrate that DOS measured CcO redox state changes are decoupled from hemoglobin concentration measurement changes.

Memory deficits associated with sublethal cyanide poisoning relative to cyanate toxicity in rodents.

Food (cassava) linamarin is metabolized into neurotoxicants cyanide and cyanate, metabolites of which we sought to elucidate the differential toxicity effects on memory. Young 6-8 weeks old male rats were treated intraperitoneally with either 2.5 mg/kg body weight (bw) cyanide (NaCN), or 50 mg/kg bw cyanate (NaOCN), or 1 µl/g bw saline, daily for 6 weeks. Short-term and long-term memories were assessed using a radial arm maze (RAM) testing paradigm. Toxic exposures had an influence on short-term working memory with fewer correct arm entries (F(2, 19) = 4.57 p < 0.05), higher working memory errors (WME) (F(2, 19) = 5.09, p < 0.05) and longer RAM navigation time (F(2, 19) = 3.91, p < 0.05) for NaOCN relative to NaCN and saline treatments. The long-term working memory was significantly impaired by cyanide with fewer correct arm entries (F(2, 19) = 7.45, p < 0.01) and increased working memory errors (F(2, 19) = 9.35 p < 0.05) in NaCN relative to NaOCN or vehicle treated animals. Reference memory was not affected by either cyanide or cyanate. Our study findings provide an experimental evidence for the biological plausibility that cassava cyanogens may induce cognition deficits. Differential patterns of memory deficits may reflect the differences in toxicity mechanisms of NaOCN relative to NaCN. Cognition deficits associated with cassava cyanogenesis may reflect a dual toxicity effect of cyanide and cyanate.

Cerebral energy metabolism during mitochondrial dysfunction induced by cyanide in piglets.

BACKGROUND: Mitochondrial dysfunction is an important factor contributing to tissue damage in both severe traumatic brain injury and ischemic stroke. This experimental study explores the possibility to diagnose the condition bedside by utilising intracerebral microdialysis and analysis of chemical variables related to energy metabolism. METHODS: Mitochondrial dysfunction was induced in piglets and evaluated by monitoring brain tissue oxygen tension (PbtO2 ) and cerebral levels of glucose, lactate, pyruvate, glutamate, and glycerol bilaterally. The biochemical variables were obtained by microdialysis and immediate enzymatic analysis. Mitochondrial function was blocked by unilateral infusion of NaCN/KCN (0.5 mol/L) through the microdialysis catheter (N = 5). As a reference, NaCl (0.5 mol/L) was infused by intracerebral microdialysis in one group of animals (N = 3). RESULTS: PbtO2 increased during cyanide infusion and returned to baseline afterwards. The lactate/pyruvate (LP) ratio increased significantly following cyanide infusion because of a marked increase in lactate level while pyruvate remained within normal limits. Glutamate and glycerol increased after cyanide infusion indicating insufficient energy metabolism and degradation of cellular membranes, respectively. CONCLUSION: Mitochondrial dysfunction is characterised by an increased LP ratio signifying a shift in cytoplasmatic redox state at normal or elevated PbtO2 . The condition is biochemically characterised by a marked increase in cerebral lactate with a normal or elevated pyruvate level. The metabolic pattern is different from cerebral ischemia, which is characterised by simultaneous decreases in intracerebral pyruvate and PbtO2 . The study supports the hypothesis that cerebral ischemia and mitochondrial dysfunction may be identified and separated at the bedside by utilising intracerebral microdialysis.

Modulation in the protein metabolism by subacute sodium cyanide intoxication in the freshwater fish, Labeo rohita (Hamilton).

The effects of exposure to one-third and one-fifth sublethal concentrations (0.106 and 0.064 mg/L) of sodium cyanide on protein metabolism on freshwater carp, Labeo rohita, was studied. Three functionally different tissues, namely, the liver, muscle, and gills, were studied after 5, 10, and 15 days. Exposures produced marked changes in protein metabolic profile in all tissues studied. These changes were more pronounced in the one-third sublethal concentration, suggesting a cumulative action of toxicant. This investigation revealed that the total, structural, and soluble proteins and urea content in all the three tissues were decreased, whereas free amino acids, ammonia, and enzyme activity (i.e., protease, alanine aminotransferase, and aspartate aminotransferase) exhibited elevated levels at both sublethal concentrations. Variation in protein metabolism in the fish, induced by sodium cyanide, demonstrated its toxic effects on cellular metabolism, thereby leading to impaired protein synthetic machinery. The results of the present study indicate that a mechanism of impaired energy transformation has direct action on the fish, L. rohita, and its impact is clearly evident from the change in the nutritional content of the fish.

Acute toxicity, behavioral and nitrogen metabolism changes of sodium cyanide affected on tissues of Tilapia mossambica (Perters).

The toxicity of sodium cyanide to the freshwater fish, Tilapia mossambica, was studied using the static bioassay method. The LC(50) value at 96 hours was found to be 44.33 µg/L (normal concentration is 25 µg/L). Behavioral changes, when exposed to a lethal concentration of sodium cyanide, showed increased opercular movement, increased surface behavior, loss of equilibrium, change in body color, increased secretion of mucus, irregular swimming activity, rapid jerk movement, "S" jerk, partial jerk, and aggressiveness. A decrease in ammonia level of gill (67.56%), muscle (63.88%), and liver (53.29%) with increased levels in urea gill (75.83%), muscle (63.53%), and liver (107.49%) was observed in a lethal concentration of sodium cyanide at the end of day 4 of exposure. In a sublethal concentration (4.43 µg/L), a decreasing trend in ammonia level continued up to day 15. Urea level at days 1 and 5 decreased on days 1 and 5, but increased on days 10 and 15.

Inhibition of ATPase activity in the freshwater fish Labeo rohita (Hamilton) exposed to sodium cyanide.

Present study concerns the effect of sodium cyanide on the Indian major carp, Labeo rohita. Fishes were exposed to lethal (0.32 mg/L) and sublethal (0.064 mg/L) concentrations of sodium cyanide. The effect of intoxication was studied on Na(+)K(+)ATPase, Mg(+2)ATPase and Ca(2+)ATPase in various physiological tissues (gill, liver, and muscle) at the end of 1, 2, 3 and 4 days of lethal and 5, 10 and 15 days of sublethal exposure periods. Sodium cyanide induced significant inhibitory effects on the ATPase activity of the fish. Inhibition of the ATPase blocked the active transport system of the gill epithelial as well as chloride cells, and thus altered the osmo-regulatory mechanism of the fish. The value of the measured responses as an indicator of stress caused by water contamination discussed. The results confirm that ATPase levels significantly decreased in treated fish, indicating that ATPases could be used as sensitive and useful biomarkers for cyanide pollution.

Respiratory distress and behavioral changes induced by sodium cyanide in the fresh water TELEOST, Cyprinus carpio (Linnaeus).

An acute toxicity (LC50) test using a static renewal bioassay method was conducted to determine the toxicity of sodium cyanide in freshwater exotic carp, Cyprinus carpio exposed for 96 h to different concentrations of sodium cyanide. The acute toxicity value was found to be 1 mg/L; one third of the LC50 (0.33 mg/L) was selected as the sublethal concentration for subacute studies. Behavioral patterns were observed in lethal (1, 2, 3, and 4 d) and sublethal concentrations (1, 5, 10, and 15 d). Cyprinus carpio in toxic media exhibited irregular, erratic, and darting swimming movements, hyperexcitability, loss of equilibrium, and sinking to the bottom, which might be due to inhibition of cytochrome c oxidase activity and decreased blood pH. The combination of cytotoxic hypoxia with lactate acidosis depresses the central nervous system and myocardium, the most sensitive critical sites for anoxia, resulting in respiratory arrest and death. A decrease in oxygen consumption (-28.36 to -78.28%; -14.22 to -47.25%) was observed at both lethal and sublethal concentrations of sodium cyanide respectively. Fish at the sublethal concentration were found under stress, but that was not fatal.

Free cyanide-induced biochemical changes in nitrogen metabolism of the Indian major carp Cirrhinus mrigala.

We studied the effect of free cyanide on several aspects of nitrogen metabolism in the gills, liver, and muscle tissue of the Indian major carp, Cirrhinus mrigala. Free amino acid levels and protease activity were elevated following exposure to lethal and sublethal doses of free cyanide. At the lethal concentration, significant changes were noticed on day 4 for both parameters. The normal condition was restored only at the sublethal concentration.

Hypoxia in presence of blockers of excitotoxicity induces a caspase-dependent neuronal necrosis.

When excitotoxic mechanisms are blocked, severe or prolonged hypoxia and hypoxia-ischemia can still kill neurons, by a mechanism which is poorly understood. We studied this "non-excitotoxic hypoxic death" in primary cultures of rat dentate gyrus neurons. Many neurons subjected to hypoxia in the presence of blockers of ionotropic glutamate receptors developed the electron microscopic features of necrosis. They showed early mitochondrial swelling, loss of mitochondrial membrane potential and cytoplasmic release of cytochrome c, followed by activation of caspase-9, and by caspase-9-dependent activation of caspase-3. Caspase inhibitors were neuroprotective. These results suggest that "non-excitotoxic hypoxic neuronal death" requires the activation in many neurons of a cell death program originating in mitochondria and leading to necrosis.

Run down of GABAergic depolarization during metabolic inhibition of rat hippocampal CA1 neurons.

We investigated the effects of metabolic inhibition on both the shift in the equilibrium potential for Cl(-) (E(Cl)) and the run down of GABA(A) receptor responses, using nystatin- and gramicidin-perforated patch-clamp recordings from rat hippocampal CA1 neurons. Metabolic inhibition with NaCN decreased outward GABAergic currents while increasing inward GABAergic currents. E(Cl) showed a positive shift almost immediately after metabolic poisoning. This shift always occurred prior to GABA receptor run down, which was observed as decreases in whole cell conductance during application of a GABA(A) receptor agonist. The results indicate that GABAergic responses tend to become depolarizing during metabolic inhibition and the run down of the GABAergic response may therefore be neuroprotective against excitotoxicity. Furthermore the results illustrate the importance of considering both changes in receptor function and current driving force, and their temporal relationship, in order to understand the physiological response of the GABAergic system during metabolic stress.

Reflex cardioventilatory responses to hypoxia in the flathead gray mullet (Mugil cephalus) and their behavioral modulation by perceived threat of predation and water turbidity.

In hypoxia, gray mullet surface to ventilate well-oxygenated water in contact with air, an adaptive response known as aquatic surface respiration (ASR). Reflex control of ASR and its behavioral modulation by perceived threat of aerial predation and turbid water were studied on mullet in a partly sheltered aquarium with free surface access. Injections of sodium cyanide (NaCN) into either the bloodstream (internal) or ventilatory water stream (external) revealed that ASR, hypoxic bradycardia, and branchial hyperventilation were stimulated by chemoreceptors sensitive to both systemic and water O2 levels. Sight of a model avian predator elicited bradycardia and hypoventilation, a fear response that inhibited reflex hyperventilation following external NaCN. The time lag to initiation of ASR following NaCN increased, but response intensity (number of events, time at the surface) was unchanged. Mullet, however, modified their behavior to surface under shelter or near the aquarium edges. Turbid water abolished the fear response and effects of the predator on gill ventilation and timing of ASR following external NaCN, presumably because of reduced visibility. However, in turbidity, mullet consistently performed ASR under shelter or near the aquarium edges. These adaptive modulations of ASR behavior would allow mullet to retain advantages of the chemoreflex when threatened by avian predators or when unable to perceive potential threats in turbidity.

Rapid sodium cyanide depletion in cell culture media: outgassing of hydrogen cyanide at physiological pH.

During the course of in vitro studies on cyanide exposure with SH-SY5Y human neuroblastoma cells, we found that sodium cyanide (NaCN) up to a concentration of 10 mM had no significant toxic effect under our culture conditions. Further investigation of this apparent cyanide resistance revealed that the sodium cyanide was being rapidly depleted from the cell culture medium. Cyanide was interacting with constituents of the cell culture medium and was somehow being detoxified or removed from solution. The reaction of cyanide with cell culture media in 96-well culture plates reduced cyanide concentrations rapidly (80-90% in 2 h at 37 degrees C). Running the same reaction in capped tubes significantly reduced cyanide loss from solution. Incubation of cyanide with individual constituents of the cell culture medium in solution showed that glucose, phenol red, and amino acids all acted to detoxify or remove cyanide from solution. When amino acids or buffers were incubated with sodium cyanide in aqueous solution at pH 7.4, hydrogen cyanide (HCN) was found to degas from the solutions. We compared HCN outgassing over a range of pH values. As expected, HCN remained very soluble at high pH, but as the pH was reduced to 7.0, the rate of HCN formation and outgassing increased dramatically. Acid-base reactions involving cyanide and proton donors, such as amino acids and other cell culture media constituents, at physiological pH result in rapid HCN outgassing from solution at 37 degrees C. These results indicate that previous in vitro cyanide toxicity studies done in standard culture media with prolonged incubation times using gas-exchanging culture containers might have to be reevaluated in light of the fact that the effective cyanide concentrations in the culture media were significantly lower than reported.

Hypoxia-induced apoptosis in adult rat dorsal root ganglion neurons in vitro.

Following spinal root injury, dorsal root ganglia suffer mechanical trauma and compromised blood supply. Little is known about the consequences for neuronal survival. Here we used cyanide treatment in vitro to examine effects of moderate hypoxia on adult rat dorsal root ganglion cells identified by GAP-43 immunostaining. 400 microM-4 mM cyanide caused sustained increases in intracellular Ca2+. Cyanide at 2 mM led to a significant increase in apoptosis, detected using TUNEL labelling and confirmed by ultrastructural analysis, and a further increase when cultures were left overnight in fresh medium. Our study shows that dorsal root ganglion neurons die by apoptosis following hypoxia and that cell death increases over time. Cyanide response provides a simple assay for testing neuroprotective agents and examining underlying mechanisms.

Glutamate neurotransmission is not required for, but may modulate, hypoxic sensitivity of pre-Bötzinger complex in vivo.

Focal hypoxia in the pre-Bötzinger complex (pre-BötC) in vivo elicits excitation of inspiratory motor output by modifying the patterning and timing of phrenic bursts. Hypoxia, however, has been reported to enhance glutamate release in some regions of the brain, including the medullary ventral respiratory column; thus the pre-BötC-mediated hypoxic respiratory excitation may result from, or be influenced by, hypoxia-induced activation of ionotropic glutamate [i.e., excitatory amino acid (EAA)] receptors. To test this possibility, the effects of focal pre-BötC hypoxia [induced by sodium cyanide (NaCN)] were examined before and after blockade of ionotropic EAA receptors [using kynurenic acid (KYN)] in this region in chloralose-anesthetized, vagotomized, mechanically ventilated cats. Before blockade of ionotropic EAA receptors, unilateral microinjection of NaCN (1 mM; 10-20 nl) into the pre-BötC produced either phasic or tonic excitation of phrenic nerve discharge. Unilateral microinjection of KYN (50-100 mM; 40 nl) decreased the amplitude and frequency of basal phrenic nerve discharge; however, subsequent microinjection of NaCN, but not DL-homocysteic acid (DLH, a glutamate analog), still produced excitation of phrenic motor output. Under these conditions, the NaCN-induced excitation included frequency modulation (FM) of phasic phrenic bursts, and in many cases, augmented and/or fractionated phrenic bursts. These findings show that the hypoxia-sensing function of the in vivo pre-BötC, which produces excitation of phrenic nerve discharge, is not dependent on activation of ionotropic glutamate receptors, but ionotropic glutamate receptor activation may modify the expression of the focal hypoxia-induced response. Thus these findings provide additional support to the concept of intrinsic hypoxic sensitivity of the pre-BötC.

Cyanide hazards to plants and animals from gold mining and related water issues.

Cyanide extraction of gold through milling of high-grade ores and heap leaching of low-grade ores requires cycling of millions of liters of alkaline water containing high concentrations of potentially toxic sodium cyanide (NaCN), free cyanide, and metal-cyanide complexes. Some milling operations result in tailings ponds of 150 ha and larger. Heap leach operations that spray or drip cyanide onto the flattened top of the ore heap require solution processing ponds of about 1 ha in surface area. Puddles of various sizes may occur on the top of heaps, where the highest concentrations of NaCN are found. Solution recovery channels are usually constructed at the base of leach heaps, some of which may be exposed. All these cyanide-containing water bodies are hazardous to wildlife, especially migratory waterfowl and bats, if not properly managed. Accidental spills of cyanide solutions into rivers and streams have produced massive kills of fish and other aquatic biota. Freshwater fish are the most cyanide-sensitive group of aquatic organisms tested, with high mortality documented at free cyanide concentrations >20 microg/L and adverse effects on swimming and reproduction at >5 microg/L. Exclusion from cyanide solutions or reductions of cyanide concentrations to nontoxic levels are the only certain methods of protecting terrestrial vertebrate wildlife from cyanide poisoning; a variety of exclusion/cyanide reduction techniques are presented and discussed. Additional research is recommended on (1) effects of low-level, long-term, cyanide intoxication in birds and mammals by oral and inhalation routes in the vicinity of high cyanide concentrations; (2) long-term effects of low concentrations of cyanide on aquatic biota; (3) adaptive resistance to cyanide; and (4) usefulness of various biochemical indicators of cyanide poisoning. To prevent flooding in mine open pits, and to enable earth moving on a large scale, it is often necessary to withdraw groundwater and use it for irrigation, discharge it to rapid infiltration basins, or, in some cases, discharge it to surface waters. Surface waters are diverted around surface mining operations. Adverse effects of groundwater drawdown include formation of sinkholes within 5 km of groundwater drawdown; reduced stream flows with reduced quantities of wate available for irrigation, stock watering, and domestic, mining and milling, and municipal uses; reduction or loss of vegetation cover for wildlife, with reduced carrying capacity for terrestrial wildlife; loss of aquatic habitat for native fishes and their prey; and disruption of Native American cultural traditions. Surface discharge of excess mine dewatering water and other waters to main waterways may contain excess quantities of arsenic, total dissolved solids, boron, copper, fluoride, and zinc. When mining operations cease, and the water pumps are dismantled, these large open pits may slowly fill with water, forming lakes. The water quality of pit lakes may present a variety of pressing environmental problems.

Effect of NaCN on currents evoked by uremic retention solutes in dissociated mouse neurons.

Uremic retention solutes possibly contribute to neuronal hypoxia/ischemia and its consequences in patients with renal failure. We examined the in vitro effects of several uremic retention solutes on murine central neurons under chemically induced metabolic hypoxia by application of sodium cyanide (NaCN). Whole cell currents were recorded using the tight-seal whole-cell voltage clamp technique. Application of NaCN caused an inward whole-cell current. From all tested toxins, which included several indoles, guanidino compounds, polyamines, purines, phenols, DL-homocysteine, orotate and myoinositol, only creatinine (CTN), guanidine (G) and guanidinosuccinic acid (GSA) produced a significant current in control and hypoxic neurons. Current evoked by GSA was significantly increased in the chemical hypoxic condition, and a synergistic effect of GSA and spermine was observed in hypoxic neurons.

Protective effect of diltiazem on cyanide-induced neurotoxicity in Wistar strain rats.

Cyanide is a well-established poison known for its rapid lethal action and toxicity. The central nervous system is one of the main target sites for cyanide toxicity. Cyanide not only alters brain biogenic amine levels but also the intracellular calcium levels in the neuronal cells. In the present study the role of calcium channel blocker diltiazem (DIL) in cyanide induced biogenic amine changes was evaluated in the Wistar strain rats. The protective effect of diltiazem pretreatment and diltiazem treatment along with cyanide on the dopaminergic system and the serotonergic system in the corpus striatum were studied. Diltiazem pretreatment was found to prevent cyanide induced changes in both the amines in the corpus striatum. These results suggest that diltiazem may mitigate the harmful effects of cyanide by interfering with influx of calcium ions and release of the biogenic amines.