Death from cardiac glycoside "pong-pong" following use as weight-loss supplement purchased on Internet.

Cerbera odollam or "pong-pong" tree contains cardiac glycosides similar to digoxin, oleander and yellow oleander. Cerbera odollam is a common method of suicide in South East Asia and has also been used as a weight loss supplement. We present a case of a 33-year-old female presenting with lethargy, vomiting, bradycardia, severe hyperkalemia of 8.9 mEq/L, slow atrial fibrillation followed by cardiovascular collapse following the ingestion of "pong-pong", the kernel of Cerbera odollam, as a weight loss supplement. Despite the administration of a total of nine vials of digoxin-specific Fab the patient could not be resuscitated. Clinicians should be aware of natural cardiac glycosides being uses as weight-loss agents and consider acute cardiac glycoside poisoning in patients with hyperkalemia, abnormal cardiovascular signs, symptoms and abnormal ECG findings.

Cerbera odollam toxicity: A review.

Cerbera odollam is a plant species of the Apocynaceae family. It is often dubbed the 'suicide tree' due to its strong cardiotoxic effects, which make it a suitable means to attempt suicide. The plant grows in wet areas in South India, Madagascar, and Southeast Asia; and its common names include Pong-Pong and Othalanga. The poison rich part of the plant is the kernel which is present at the core of its fruit. The bioactive toxin in the plant is cerberin, which is a cardiac glycoside of the cardenolide class. Cerberin has a mechanism of action similar to digoxin; hence, Cerbera odollam toxicity manifests similar to acute digoxin poisoning. Ingestion of its kernel causes nausea, vomiting, hyperkalemia, thrombocytopenia, and ECG abnormalities. Exposure to high doses of Cerbera odollam carries the highest risk of mortality. Initial management includes supportive therapy and administration of atropine followed by temporary pacemaker insertion. Administration of digoxin immune Fab may be considered in severe cases, although efficacy is variable and data limited to isolated case reports.

Toxicity of the spiny thick-foot Pachypodium.

PREMISE OF THE STUDY: Pachypodium (Apocynaceae) is a genus of iconic stem-succulent and poisonous plants endemic to Madagascar and southern Africa. We tested hypotheses about the mode of action and macroevolution of toxicity in this group. We further hypothesized that while monarch butterflies are highly resistant to cardenolide toxins (a type of cardiac glycoside) from American Asclepias, they may be negatively affected by Pachypodium defenses, which evolved independently. METHODS: We grew 16 of 21 known Pachypodium spp. and quantified putative cardenolides by HPLC and also by inhibition of animal Na+ /K+ -ATPase (the physiological target of cardiac glycosides) using an in vitro assay. Pachypodium extracts were tested against monarch caterpillars in a feeding bioassay. We also tested four Asclepias spp. and five Pachypodium spp. extracts, contrasting inhibition of the cardenolide-sensitive porcine Na+ /K+ -ATPase to the monarch's resistant form. KEY RESULTS: We found evidence for low cardenolides by HPLC, but substantial toxicity when extracts were assayed on Na+ /K+ -ATPases. Toxicity showed phylogenetic signal, and taller species showed greater toxicity (this was marginal after phylogenetic correction). Application of Pachypodium extracts to milkweed leaves reduced monarch growth, and this was predicted by inhibition of the sensitive Na+ /K+ -ATPase in phylogenetic analyses. Asclepias extracts were 100-fold less potent against the monarch compared to the porcine Na+ /K+ -ATPase, but this difference was absent for Pachypodium extracts. CONCLUSIONS: Pachypodium contains potent toxicity capable of inhibiting sensitive and cardenolide-adapted Na+ /K+ -ATPases. Given the monarch's sensitivity to Pachypodium, we suggest that these plants contain novel cardiac glycosides or other compounds that facilitate toxicity by binding to Na+ /K+ -ATPases.

Potato disc bioassay and cytotoxic effect of Leptadenia pyrotechnica: comparative study of diverse extracts.

Comparative acute toxicity studies of the latex and sequential extracts of Leptadenia pyrotechnica (Forsk.) Decne (Asclepiadaceae) were recorded using brine shrimp. The higher toxicities were exhibited in latex; methanol, methanol/dichloromethane (1:1), defatted methanol/dichloromethane (1:1), defatted methanol and dichloromethane extracts. The other extracts; aqueous, alkaloids, ethyl acetate and n-butanol exhibited less toxicities compared with the other extracts. The estimated LC50 and its 95% confidence limits for these extracts expressed in ppm were: methanol, latex 18.84 (11.22-31.61), methanol/dichloromethane 19.95 (7.76-53.70), defatted methanol/dichloromethane 21.38 (7.24-63.10), defatted methanol 28.19 (16.27-48.81) and dichloromethane 30.90 (11.75-79.43). The anti-tumor activities; potato disc assays of methanol, ethyl acetate and alkaloids extracts showed good activities as anti-tumor agent which represented-49.30,-43.20 an -33.60%, respectively. While latex and aqueous extract represented-30.80 and-28.17%, respectively.

Pathological effects of Cryptostegia venusta toxicity in goats and rats.

Here, we aimed to determine the toxicity of Cryptostegia venusta in goats and rats. We orally administered a single 60 g dose of shredded C. venusta leaves per kilogram of body weight to three goats. The animals were necropsied after death, and tissue sections were collected and routinely processed for histopathological analyses. Additionally, we separated 25 adult male Wistar rats (each weighing about 150 g) into five groups: an untreated control group and groups orally treated with 1, 3, 10, or 60 g/kg doses. Rats were sacrificed 72 h after administration of the C. venusta extract, and tissue sections collected for histopathological analyses. All goats presented signs of apathy, salivation, frequent urination, and eventually fatigue 4-6h after receiving C. venusta. Two goats died 20 h after administration, and the third was sacrificed in extremis. The only histopathological finding observed in the goats was lung edema. No rats died during the experimental period or presented any clinical signs or macroscopic lesions. However, both goats and rats exhibited degeneration and multifocal necrosis of cardiac muscle fibers. From our results, we conclude that the C. venusta plant is capable of promoting cardiotoxicity.

Evaluation of the toxicity and reversibility profile of the aqueous seed extract of Hunteria umbellata (K. Schum.) Hallier f. in rodents.

Hunteria umbellata (K. Schum.) Hallier f. (family: Apocynaceae) is reputed for the folkloric management of labour, pain and swellings, stomach ulcers, diabetes, obesity, and anaemia, with no scientific report of its toxicity and reversibility profile. The present study was, therefore, aimed at investigating the in vivo toxicity and reversibility profile of the aqueous seed extract of Hunteria umbellata (HU). The acute oral and intraperitoneal toxicity studies of HU were determined in Swiss albino mice while its 90-day oral toxicity and toxicity reversibility profile on anthropometric, biochemical, haematological and histopathological parameters were also assessed using standard procedures. Results showed that the LD50 values for the acute oral and intraperitoneal toxicity studies for HU were estimated to be 1000 mg/kg and 459.3 mg/kg, respectively. Visible signs of immediate and delayed toxicities including starry hair coat, respiratory distress, and dyskinesia were observed. For the chronic oral toxicity study, HU administered for 90 days produced significant (p < 0.001) reductions in the weight gain pattern and significant (p < 0.001) and dose related increases in the relative weights of liver, stomach, spleen, testis, lungs and heart, at the 100 and 500 mg/kg of HU. Chronic HU treatment also produced significant (p < 0.05, p < 0.001) dose related reductions in the serum levels of fasting blood glucose, bicarbonate, urea and creatinine while causing non-significant (p > 0.05) alterations in the serum levels of sodium, potassium, alaninine transaminase, aspartate transaminase, alkaline phosphatase, total and conjugated bilirubin, total protein and albumin. Also, chronic oral treatment with HU produced significant (p < 0.05, p < 0.01, p < 0.001) and dose-related increases in the red cell count, packed cell volume, haemoglobin concentration, platelet count, total leucocyte count and lymphocyte differential while producing significant (p < 0.05) reductions in neutrophil and granulocyte differentials. HU also produced histological features of proliferations of the stomach epithelia, lung tissues, splenic white and red pulps, and testicular spermatogenic series. Following 14 days of oral toxicity reversibility test, there was no significant (p>0.05) reversal in the serum levels of the biochemical and haematological parameters investigated, including the HU-induced histological lesions. Overall, results of this study showed that HU has a relatively low oral toxicity profile but its prolonged use, particularly, at high doses should be with great caution.

Evaluation of valuation of toxicity profile of an alkaloidal fraction of the stem bark of Picralima nitida (fam. Apocynacaes).

Dermal and acute toxicity evaluation of the basic alkaloidal fraction of the stem bark of Picralima nitida, which has been shown to have pronounced activity against causative organisms of dermatomycosis in man, was carried out in animals. Acute intraperitoneal toxicity tests showed a dose-dependent toxicity. There was inflammation and necrosis of liver hepatocytes accompanied by reduction in neutrophilic count and a corresponding increase in lymphocytic count. There was no sign of reddening or irritation when applied into the eye conjunctiva. Dermal tests also showed that the fraction caused no sensitization, inflammation or death in the animal models used.

Toxicity of Nerium oleander and Rhazya stricta in Najdi sheep: hematologic and clinicopathologic alterations.

The toxic effects of oral administration of 0.25 g/kg Nerium oleander leaves, 0.25 g/kg Rhazya stricta leaves or their mixture at 0.25 g/kg N. oleander leaves plus 0.25 g/kg R. stricta leaves on Najdi sheep were investigated. Daily oral dosing of R. stricta leaves for 42 days was not fatal to sheep while single oral doses of either N. oleander leaves or the mixture with R. stricta leaves proved fatal to animals within 24 hours with dyspnea, grunting, salivation, grinding of the teeth, ruminal bloat, frequent urination, ataxia and recumbency prior to death. The main lesions were widespread congestion or hemorrhage, pulmonary cyanosis, emphysema, bronchotracheal froths, and hepatonephropathy. The clinical and pathological changes were correlated with alterations in serum LDH and AST activities and concentrations of cholesterol, bilirubin, urea, total protein, albumin, and globulin and hematological values.