Cleistanthus collinus poisoning affects mitochondrial respiration and induces oxidative stress in the rat kidney.

Cleistanthus collinus is a poisonous shrub used for deliberate self-harm in rural areas of South India and intake of boiled decoction of leaves is a common method of self-harm. Distal renal tubular acidosis (dRTA) is an important clinical symptom observed in C. collinus poisoning, and renal V-ATPases may be potential targets of damage. However, a lack of understanding of molecular mediators involved hampers medical management, which is mainly supportive. We hypothesized that C. collinus poisoning induces renal oxidative stress; probably by inducing mitochondrial uncoupling, which compromises V-ATPase activity to ultimately produce dRTA. This was tested by exposing renal BBMV, kidney cells in culture, and Wistar rats to C. collinus poisoning. Exposure to C. collinus aqueous extract resulted in significant elevations in the lipid peroxidation marker, conjugated dienes, in cell culture and in vivo. A significant decrease in mitochondrial respiratory control ratio was observed in kidneys from C. collinus-treated animals suggesting that mitochondrial oxidative phosphorylation is uncoupled. This was accompanied by significant increase in ADP levels and a decrease in proton pump activity. Thus, these results demonstrate that C. collinus poisoning induces oxidative stress which influences proton pump activity, probably due to feedback inhibition by elevated ADP levels because of mitochondrial dysfunction in the rat kidney.

Fatal Cleistanthus collinus toxicity: a case report and review of literature.

Cleistanthus collinus is an extremely toxic plant poison. We report a case of suicidal ingestion of boiled water decoction of C. collinus where the patient presented with abdominal pain and giddiness. There was persistent metabolic acidosis and fluctuation in the level of serum potassium. The ECG changes indicated a probable myocardial injury with conduction abnormality. At autopsy, the viscera were found to be congested. The toxins were detected in the viscera and blood by TLC and HPLC. Cleistanthin A and B, collinusin, and diphyllin are the principal toxic constituents of the plant. Consumption of a boiled decoction of leaves is highly toxic and, medical management of patients is mainly supportive because the molecular mechanisms of toxin action are unknown. In the recent years, C. collinus has created a considerable amount of interest because of its complex metabolites and their cytotoxic activities. Through this study, the authors have tried to highlight different properties pertaining to C. collinus.

Pattern and outcome of Cleistanthus collinus (Oduvanthalai) poisoning in a tertiary care teaching hospital in South India.

There is paucity of information on human studies about Cleistanthus collinus (Oduvanthalai) poisoning at global level. The present study was done to find out the pattern and outcomes with acute poisoning of this plant poison. Retrospective record based study was conducted among acute C. collinus (Oduvanthalai) poisoning cases admitted between January 2010 and December 2010 in a tertiary care teaching hospital in South India. A total of 51 cases were analyzed with 52.9% of them being females and 51% belonged to 21-40 years age group. Interpersonal conflict was the stressor for poisoning in 76% cases. Mortality rate was 17.6% with a median duration of 3.5 days from time of ingestion. Majority of the patients who died during hospitalization had ingested decoction (77.8%), and had neurological manifestations (77.8%), hypokalemia (77.8%), neutrophilia (66.7%), leucocyotosis (55.6%) and elevated blood urea (77.8%). It was found that lower potassium level, white blood cell and neutrophil count were significantly associated with mortality due to poisoning.

Mechanisms of toxicity of Cleistanthus collinus: vacuolar ATPases are a putative target.

Ingestion of Cleistanthus collinus, a shrub native to South India, either intentionally or accidentally, is a common cause of death in the area. Consumption of a boiled decoction of leaves is highly toxic, but medical management of patients is mainly supportive because the molecular mechanisms of toxin action are unknown. Distal renal tubular acidosis is one of the symptoms of poisoning in patients and adenosine triphosphate (ATP) requiring proton pumps is important for acid secretion in the kidney. Hence, we hypothesized that these may be putative targets for C. collinus action and we tested this by exposing rat renal brush border membrane (BBM) as well as cultured kidney cells to a boiled decoction of C. collinus. Exposure to the C. collinus decoction resulted in significant inhibition of vacuolar type H(+)-ATPase (V-ATPase) activity in renal BBM as well as blocking of the proton pump in renal BBM vesicles. C. collinus decoction was also found to inhibit acidification of intracellular organelles in cells in culture, similar to the effect seen with either bafilomycin or concanamycin - specific inhibitors of the V-ATPase. This was accompanied by a decrease in V-ATPase activity, but an increase in protein levels. These results demonstrate that the V-ATPase in renal cells is a putative target for the toxins in C. collinus and the inhibition of this important proton pump probably plays a role in the development of distal renal tubular acidosis and subsequent renal failure seen in poisoned patients.

A clinical study of renal tubular dysfunction in Cleistanthus collinus (Oduvanthalai) poisoning.

INTRODUCTION: Self-poisoning through the ingestion of Oduvanthalai is common in South India. Mortality may occur because of arrhythmias, renal failure, shock, and respiratory distress. The mechanisms of toxicity are unclear. This prospective, clinical study was designed to assess renal tubular dysfunction because of Oduvanthalai poisoning. METHODS: Thirty-two consecutive patients admitted with Oduvanthalai poisoning at a tertiary care hospital in South India, from June 2007 to August 2009 (26 months), were evaluated through history, physical examination, and laboratory studies. Following an interim analysis, additional studies of renal tubular function were performed on a subcohort of eight patients. These included the following: (1) urinary pH, daily serum, and urine anion gap; (2) 24-h urine protein and potassium; and (3) assessment of urine hexosaminidase and amino acid levels. RESULTS: Metabolic acidosis (100%), which persisted at discharge (65.6%), hypokalemia (62.5%), and renal failure (15.6%), was apparent in the total cohort. Tests of renal tubular function on the subcohort revealed a normal anion gap, hyperchloremic, metabolic acidosis of renal etiology, defective urinary acidification, and hypokalemia with kaliuresis, indicative of distal renal tubular acidosis in six patients. Urinary hexosaminidase and amino acid levels, markers of proximal tubular dysfunction, were elevated in seven and two patients, respectively. CONCLUSIONS: Distal renal tubular acidosis is an important feature of Oduvanthalai poisoning. Proximal tubular injury and, in more severe forms, global tubular dysfunction with diminished glomerular filtration rate may occur.

Epidemiology of Cleistanthus collinus (oduvan) poisoning: clinical features and risk factors for mortality.

Cleistanthus collinus (local name: oduvan) poisoning is a common suicidal poisoning method used in rural southern India. There are few studies on this issue and they have small sample sizes. This study examines the epidemiology of oduvan poisoning in a large sample, highlighting socio-demographic and clinical profile, complications, and risk factors for mortality. This study is a retrospective case series of 127 oduvan intentionally poisoned patients presenting at a tertiary care teaching hospital between the years 1990-1999. Descriptive statistics, cumulative case fatality rates and time to death from ingestion of poison were calculated. Cox regression adjusting for left truncation was used to investigate the effects of covariates on death. Patients' average (sd) age was 29.1 (10.9), 62% were female, 76% were married and 49% were housewives. The cumulative case fatality rate was 30%. The median time to death after oduvan ingestion was 3 days. Common signs and symptoms included hypokalaemia, vomiting, hyponatraemia, altered sensorium, bradycardia and abnormal ECG. There was a 58% risk reduction (95% CI: 29-75) in death with each 1 mmol/l increase in plasma potassium level. Patient's age was associated with an increased risk of death and the estimated hazard ratio for an increase of 10 years in age was 1.56 (95% CI: 1.18-2.07). Use of boiled oduvan extract was associated with an increased mortality (HR: 2.71, 95% CI: 1.17-6.32) compared to ingesting fresh leaves. Risk factors for oduvan poisoning mortality were hypokalaemia, older age, mode of consumption and an elevated risk for death with presence of chronic disease. When consumed as a boiled extract, oduvan is more lethal. We recommend close monitoring, correction of plasma potassium and appropriate supportive measures.

Hepatotoxicity caused by Breynia officinalis.

Breynia officinalis has the Chinese proprietary name, Chi R Yun, which means dizziness or vertigo for 7 d. In daily practice, it has been used to treat venereal diseases, contusion, heart failure, growth retardation and conjunctivitis in combination with other traditional Chinese medicines. Two hospital-based cases of Breynia officinalis poisoning have been reported to the Poison Control Center. Case 1 was a 43-y-old female who consumed a mixture of 1500 g lower stem and root of Ji Mu Ju in boiled water in a suicide attempt. Her AST reached 264 and ALT reached 2443. Case 2 was a 51-y-old female who consumed 20 pieces of lower stem and root of Ji Mu Ju stewed with meat and 100 ml of wine to treat chronic contact dermatitis. Her AST reached 3815 and ALT reached 6625. In both cases Breynia officinalis was identified as the cause of poisoning. Poisoning in humans involves the neurologic, gastrointestinal, hepatic, urinary and respiratory systems. Hepatotoxic effects have been reported for some Chinese herbal medicines, but not Breynia officinalis: Breynia officinalis poisoning causes hepatocellular liver injury rather than cholestatic liver injury.

The spectrum of ocular inflammation caused by euphorbia plant sap.

OBJECTIVE: To report the spectrum of clinical findings in patients with ocular inflammation caused by plant sap from Euphorbia species. DESIGN: Clinical case series. SETTING: Ophthalmology emergency referrals in the United Kingdom. PATIENTS: We examined 7 patients, all of whom gave a history of recent ocular exposure to the sap of Euphorbia species. INTERVENTIONS: All patients were treated with antibiotic drops or ointment (chloramphenicol). Cycloplegic and steroid drops were also used for some patients. Patients were observed until all signs and symptoms had resolved. MAIN OUTCOME MEASURES: Symptoms, visual acuity, and clinical signs of inflammation. All patients provided a specimen of the plant for formal identification. RESULTS: Initial symptoms were generally burning or stinging pain with blurred vision. In most cases, visual acuity was reduced between 1 and 2 Snellen lines. In 1 patient with age-related maculopathy, acuity dropped from 20/80 to hand motions before recovering. Clinical findings varied from a mild epithelial keratoconjunctivitis to a severe keratitis with stromal edema, epithelial sloughing, and anterior uveitis. All signs and symptoms had resolved by 1 to 2 weeks. CONCLUSIONS: These cases illustrate the range of severity of Euphorbia sap keratouveitis. The condition seems to be self-limiting when managed supportively. People who work with Euphorbia plant species should wear eye protection. Clinicians managing keratopathy caused by Euphorbia species should be aware of the danger of sight-threatening infection and uveitis, particularly during the first few days.