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Toxic potential of oleander derived compost and vegetables grown with oleander soil amendments.

California recycles 50% of previously disposed trash. Increased use of yardwastes and composts has raised concern about toxic materials in these products. Oleander is a toxic shrub common to CA landscapes and is frequently clipped and disposed of in greenwaste containers, resulting in concerns about the toxicity of oleander-contaminated yardwastes and composts from these wastes. Information about breakdown of oleandrin (one of the glycoside toxicants of oleander) during composting or the ability of plants to absorb this molecule has not been reported. In separate experiments, we documented the apparent first-order disappearance of oleandrin from composts of pure oleander, with a disappearance half-life of 15 d. Within 50 d, 90% of the oleandrin was removed during aerobic composting in a turned pile. In an amendment study with fresh uncomposted oleander, no oleandrin was detected in tomato and zuchinni fruit, snap beans, carrot tubers, or green lettuce. Oleandrin was found in red leaf lettuce growing in soils mulched with oleander, but oleandrin concentrations were near the detection limit of the assay. Soil from oleander mulched and amended plots contained low levels of oleandrin at the time of harvest.

California↗

Oleander toxicity: an examination of human and animal toxic exposures.

The oleander is an attractive and hardy shrub that thrives in tropical and subtropical regions. The common pink oleander, Nerium oleander, and the yellow oleander, Thevetia peruviana, are the principle oleander representatives of the family Apocynaceae. Oleanders contain within their tissues cardenolides that are capable of exerting positive inotropic effects on the hearts of animals and humans. The cardiotonic properties of oleanders have been exploited therapeutically and as an instrument of suicide since antiquity. The basis for the physiological action of the oleander cardenolides is similar to that of the classic digitalis glycosides, i.e. inhibition of plasmalemma Na+,K+ ATPase. Differences in toxicity and extracardiac effects exist between the oleander and digitalis cardenolides, however. Toxic exposures of humans and wildlife to oleander cardenolides occur with regularity throughout geographic regions where these plants grow. The human mortality associated with oleander ingestion is generally very low, even in cases of intentional consumption (suicide attempts). Experimental animal models have been successfully utilized to evaluate various treatment protocols designed to manage toxic oleander exposures. The data reviewed here indicate that small children and domestic livestock are at increased risk of oleander poisoning. Both experimental and established therapeutic measures involved in detoxification are discussed.

Animals↗

Activated charcoal is effective but equilibrium dialysis is ineffective in removing oleander leaf extract and oleandrin from human serum: monitoring the effect by measuring apparent digoxin concentration.

Accidental poisoning from oleander leaf or oleander tea can be life threatening. The authors studied the effectiveness of activated charcoal and equilibrium dialysis in removing oleander leaf extract and commercially available oleandrin as well as oleandrigenin, the active components of oleander plant, from human serum. Oleander leaf extract was prepared in distilled water and drug-free serum was supplemented with the extract. Then serum was treated with activated charcoal at room temperature and an aliquot was removed at 0 minutes, 10 minutes, 20 minutes, and finally 30 minutes to study the presence of oleander extract by measuring the apparent digoxin concentration using the FPIA for digoxin. The authors observed effective removal of oleander extract by activated charcoal. When the authors supplemented other drug-free serum pools with pure oleandrin or oleandrigenin and then subsequently treated them with activated charcoal, the authors observed complete removal of digoxin-like immunoreactivity at the end of 30 minutes' treatment. When drug-free serum pool supplemented with either oleander leaf extract, oleandrin, or oleandrigenin was passed through a small column packed with activated charcoal, the authors observed almost no apparent digoxin concentration following the passage through the column indicating that activated charcoal is very effective in removing oleander from human serum in vitro. In contrast, when serum pools containing either oleander leaf extract or oleandrin were subjected to equilibrium dialysis against phosphate buffer at pH 7.4, the authors observed no significant reduction in apparent digoxin concentration even after 24 hours. The authors conclude that activated charcoal is effective but equilibrium dialysis is ineffective in removing oleander leaf extract from human serum.

Cardenolides↗

Effect of selected insecticides on Homalodisca coagulata (Homoptera: Cicadellidae) and transmission of oleander leaf scorch in a greenhouse study.

Homalodisca coagulata (Say) is a recent introduction to California. It is known to spread a strain of the bacterium Xylella fastidiosa Wells, Raju, Hung, Weisberg, Mandelco-Paul & Brenner that induces oleander leaf scorch disease in oleander, Nerium oleander L. Oleander leaf scorch is lethal to oleander and threatens to decimate one of the most important landscape shrubs in California. Towards developing a management strategy for H. coagulata-spread oleander leaf scorch, we documented the affects of selected insecticides on H. coagulata mortality, feeding behavior, and disease transmission in a greenhouse study. Oleanders treated with fenpropathrin, fenpropathrin + acephate, and imidacloprid caused significant mortality to caged H. coagulata within 4 h of exposure. Within 24 h, these pesticides caused nearly 100% mortality 3 wk after treatment. In other experiments, acetamiprid and fenpropathrin treatments reduced time spent feeding and total time on plants. H. coagulata on fenpropathrin-, acetamiprid-, and imidacloprid-treated oleander died in less than 13 min on average. Oleander leaf scorch transmission by H. coagulata was blocked by applications of foliar-applied acetamiprid, and soil-applied imidacloprid and thiamethoxam.

Animals↗

Effects of the sap of the common oleander Nerium indicum (Apocyanaceae) on male fertility and spermatogenesis in the oriental tobacco budworm Helicoverpa assulta (Lepidoptera, Noctuidae).

We investigated the effects of sap of the common oleander Nerium indicum (Apocyanaceae) on male fertility and spermatogenesis in the oriental tobacco budworm Helicoverpa assulta. We found that continuous feeding of oleander sap during the larval period significantly affects fertility in males but not in females. This effect was also induced by direct injection of oleander sap into the hemocoel of 2-day-old pupae. Histological analyses of developing testes following oleander injection revealed a developmental delay and progressively more severe morphological abnormalities in the later stages of development. The effects of oleander sap on spermatogenesis in H. assulta were associated with greatly reduced levels of the two major polyamines, spermidine and spermine, in testis compared with saline-injected controls. In contrast, levels of putrescine, which is a precursor of both spermidine and spermine, and the activities of the enzymes ornithine decarboxylase and arginine decarboxylase, which are involved in the biosynthesis of putrescine, were initially elevated following oleander injection, but subsequently failed to undergo the induction that normally occurs during late pupal development. The effects of oleander sap on spermidine and spermine levels could be the result of direct inhibition by chemical constituents of the oleander sap of one of the enzymes used in common in the conversions of putrescine to spermidine and spermidine to spermine; alternatively, these effects on polyamine metabolism could be secondary to the disruption of a more fundamental process in the developmental program guiding spermatogenesis in H. assulta.

Animals↗

Fructose-1,6-diphosphate in the treatment of oleander toxicity in dogs.

Oleander, a flowering plant that grows in the Mediterranean and southern US, contains the cardiac glycosides oleandrin, digitoxigenin and nerium, which inhibit Na(+)-K+ ATPase. Clinical manifestations of oleander toxicity include gastrointestinal irritation, marked hyperkalemia, A-V block, ventricular dysrhythmia, and not uncommonly death. Because fructose-1,6-diphosphate (FDP) has been shown to attenuate digoxin toxicity, we determined whether this agent would be effective in the treatment of the toxicity of these similarly-structured cardiac glycosides. Anesthetized dogs (n = 12) were infused i.v. for 5 min with 40 mg oleander extract/kg and then 6 dogs randomly selected from that group received a 50 mg/kg bolus of 10% FDP followed by a constant infusion. The other control animals received the same dosage of 10% dextrose. Within 5 min after oleander administration, all dogs developed dysrhythmias. The FDP-treated animals reverted to sinus rhythm within 1.58 +/- 0.15 h; none in the control group returned to sinus rhythm. One control dog died at 3 h from ventricular fibrillation. Marked hyperkalemia was observed in the control group; plasma K+ remained unchanged in the FDP group. Throughout the 4 h experimental period the FDP group maintained normal arterial pressures; in the control dextrose group, pressures were profoundly depressed. Cardiac output declined in both groups but remained higher in the FDP group. To determine the mechanism whereby FDP attenuates oleander toxicity, we studied the in vitro effect of FDP on oleander poisoned myocardial sarcolemmal membranes. At concentrations of 1 and 2 mg oleander inhibited Na(+)-K+ ATPase activity and addition of 500 microM FDP restored myocardial sarcolemmal Na(+)-K+ ATPase function. FDP effectively prevented hyperkalemia, reversed dysrhythmias and improved hemodynamics in vivo in this canine model of oleander toxicity and also restored sarcolemmal Na(+)-K+ ATPase activity in vitro.

Animals↗

Oleander poisoning.

The two common oleanders, Thevetia peruviana and Nerium oleander, contain a mixture of poisons including cardiac glycosides, and are extremely toxic. They are cultivated universally throughout Australia, and rank equally with mushrooms as the major cause of children's admission to hospital after accidental plant ingestions. A seven-year total population survey from south-east Queensland has revealed that, in practice, the rate of clinical poisoning due to oleander is inconsequential, and mortality is negligible. The annual age-specific admission rate for children (aged from birth to 12 years of age), for all plant ingestions is 2.33 per 100 000, and 0.62 per 100 000 specifically for oleander. Oleander ingestion causes a syndrome of combine cardiac and gastrointestinal symptoms and signs. A case series of 13 children is described, and the clinical features summarized. After accidental oleander ingestion, current experience indicates that the prognosis is excellent.

Antidotes↗

Characterisation of acyl-ACP desaturases from Macadamia integrifolia Maiden & Betche and Nerium oleander L.

The seed oil in Macadamia integrifolia contains about 30% palmitoleic acid (16:1(Delta9)) and Nerium oleander about 12% isoricinoleic acid (Delta9-hydroxy-18:1(Delta12)). It has been shown that palmitoleic acid can be produced by acyl-acyl carrier protein (ACP) desaturases and it has also been shown that fatty acid hydroxylation can occur via direct substitution of a hydrogen atom. Therefore it seemed possible that the enzymes responsible for the making of these unusual fatty acids in M. integrifolia and N. oleander were of acyl-ACP desaturase type. Extracts from developing M. integrifolia developing seeds showed a relative ratio of 16:0-ACP to 18:0-ACP desaturation that was about 13 times higher than in sunflower seeds. N. oleander seed extracts catalysed conversion of 18:0-ACP to 18:1(Delta9) but only trace amounts of Delta9-hydroxy fatty acids were formed. A total of four cDNAs were isolated from developing seeds, of both species, using a fragment isolated with PCR amplification. The M. integrifolia acyl-ACP desaturase cDNA was expressed in Escherichia coli. A partly purified fraction of the enzyme showed a 16:0-ACP to 18:0-ACP desaturation ratio about 90-fold less than that in the Macadamia extracts. Expressed N. oleander acyl-ACP desaturase cDNAs showed predominantly 18:0-ACP desaturase activity and no hydroxylase activity. Thus it is not likely that any of the four acyl-ACP desaturases cloned from M. integrifolia or N. oleander is involved in the production of unusual fatty acids.

Journal Article↗

Oleander tea: herbal draught of death.

A woman died after drinking herbal tea prepared from oleander (Nerium oleander) leaves. This case demonstrates the cross-reactivity between the cardiac glycosides in oleander and the digoxin radioimmunoassay. Digoxin-specific Fab antibody fragments have not been used in oleander poisoning, but these might prove to be lifesaving. Treatment of oleander toxicity is aimed at controlling arrhythmias and hyperkalemia; inactivation of the Na-K ATPase pump, however, can make treatment difficult.

Adult↗

Rapid detection of oleander poisoning using fluorescence polarization immunoassay for digitoxin. Effect of treatment with digoxin-specific Fab antibody fragment (ovine).

Poisoning from the oleander plant is common. Taking advantage of the high cross-reactivity of oleandrin, the major cardiac glycoside found in the oleander plant, we demonstrated that the serum digitoxin assay can be successfully used for the rapid diagnosis of oleander poisoning. Digitoxin is rarely used for treatment of cardiac disorders in the United States and has a therapeutic range of 19.7 to 39.3 nmol/L. In a typical oleander poisoning, serum oleandrin concentrations may reach 174 mmol/L or more. A serum specimen supplemented with 174 mmol/L of oleandrin containing no digitoxin showed an apparent digitoxin concentration of 1,272.1 nmol/L, a very high value compared with the range of the serum digitoxin assay, which is 2.6 to 104.8 nmol/L. Moreover, the response of the serum digitoxin assay with serum specimens containing various concentrations of oleandrin (and no digitoxin) is linear. Therefore, the oleandrin concentration in serum can be calculated from the apparent digitoxin concentration to access the severity of poisoning. Recently, the usefulness of the digoxin-specific Fab antibody fragment in the treatment of oleander poisoning has been described; however, no laboratory test was performed to demonstrate the progress of therapy. We demonstrated that the digoxin-specific Fab antibody can bind oleandrin in vitro, thus reducing the pharmacologically active free oleandrin. Because Fab and oleandrin bound to Fab are absent in the protein-free ultrafiltrates, monitoring the activity of free oleandrin in the ultrafiltrates can be used for monitoring the effectiveness of therapy.

Cardenolides↗

Acute toxicity of various oral doses of dried Nerium oleander leaves in sheep.

The acute toxicity of dried Nerium oleander leaves to Najdi sheep is described in 12 sheep assigned as untreated controls, N. oleander-treated once at 1 and 0.25 g/kg body weight and N. oleander-treated daily at 0.06 g/kg body weight by drench. Single oral doses of 1 or 0.25 g of dried N. oleander leaves/kg body weight caused restlessness, chewing movements of the jaws, dyspnea, ruminal bloat, incoordination of movements, limb paresis, recumbency and death 4-24 hr after dosing. Lesions were widespread congestion or hemorrhage, pulmonary cyanosis and emphysema, hepatorenal fatty change and catarrhal abomasitis and enteritis. The daily oral doses of 0.06 g dried N. oleander leaves/kg body weight caused less severe signs and death occurred between days 3 and 14. In these animals, the main lesions were hepatonephropathy and gelatinization of the renal pelvis and mesentry and were accompanied by significant increases in serum AST and LDH activities, in bilirubin, cholesterol and urea concentrations and significant decreases in total protein and albumin levels, anemia and leucopenia.

Acute Disease↗

Diagnosis of oleander poisoning in livestock.

Since mid-1989, 37 cases of oleander poisoning in livestock have been diagnosed at the California Veterinary Diagnostic Laboratory System. The most frequent source for oleander exposure was plant clippings. Sudden death was the most common presenting complaint. Other signs reported included diarrhea, pulmonary edema, tachycardia, cardiac arrhythmias, colic, and lethargy. In the past, a presumptive diagnosis of oleander poisoning could be based only on matching clinical signs with evidence of consumption of oleander. A new 2 dimensional Thin-layer chromatography analysis of ingesta for oleandrin and an awareness of lesions in heart muscle have greatly improved the ability to diagnose oleander toxicosis.

Animal Feed↗

Oleander interference in the digoxin radioimmunoassay in a fatal ingestion.

An elderly woman allegedly ingested oleander leaves and died. Ventricular arrhythmias and asystole were unresponsive to cardiopulmonary resuscitation, pharmacologic agents, and cardioversion. The patient, who had no access to digoxin, had an initial serum digoxin concentration of 5.8 ng/mL. Cross-reactivities between oleander extract and pure oleandrin and digoxin in the digoxin radioimmunoassay were 100:1 and 29,000:1, respectively. We postulate that glycosides in oleander leaves produced the elevated serum digoxin concentration. Based on an assumed volume of distribution of the oleander glycosides of 1 L/kg, the calculated lethal dose absorbed by our patient was 200 times greater than lethal doses in several animal species and corresponded to the absorption of 4 g of oleander leaves.

Aged↗

Transitory complete atrioventricular block associated to ingestion of Nerium oleander.

BACKGROUND: Self-medication with plants can lead to severe poisoning. Oleander (Nerium oleander) is an ornamental plant whose toxicity to man is due to a mixture of nondigitalis cardiac glycosides. The clinical manifestations of oleander poisoning combine cardiac and gastrointestinal symptoms, and are similar to those of a digitalis overdose. CASE REPORT: Following the ingestion of tea made of the leaves of oleander, a 33-year-old woman developed dizziness, vomiting and abdominal cramps as main symptoms, and complete atrioventricular block that reverted within 24 hours. She remained with bradycardia, dizziness and diarrhea for about 6 days. On admission she had a serum potassium of 6.7 mEq/L and a serum creatinine of 2.3 mg%, that progressively returned to normal levels. CONCLUSION: Clinicians must include oleander poisoning in the differential diagnosis of bradyarrhythmias, particularly in children and young people without known cardiovascular disease, in areas where this plant either is used as a herbal medicine or is known as poisonous.

Adult↗