Star fruit

Soy phytoestrogensf Jering fruit Pennyroyal oil Squirting cucumberf Star fruit... 

In 2000 Chang JM et al [5] reported 19 patients with renal failure under dialysis and one also with renal failure but in supportive treatment who after star fruit ingestion developed signs and symptoms of intoxication such as hiccups, mental confusion, paresis, muscular weakness and convulsions. Eight of those patients died (including the patient in supportive treatment)... 

Star fruit intoxication can be classified into three levels according to signs and symptoms that might provide a useful guideline for institution of proper treatment mild, moderate and severe (Table 2). 

Certain cases of mild intoxication progress to a severe level if patients are not treated and the velocity of progression is extremely variable, depending on the characteristics of each patient. In some cases this progression happens with less than 24 hours after star fruit ingestion [5, 13, 9, 10, 15, 17, 18, 19]. Therefore,... 

Table 2. Clinical levels of star fruit intoxication.

Although star fruit has enriched potassium content, hyperkalemia has not been suggested as causing of death in reported cases [5,13]. 

Seizures are present in 30% of patients with star fruit intoxication [17], and most patients have convulsive [6, 8,10,11,13,14,17,18,19] or non-convulsive [16] status epilepticus. The mortality rate of patients with seizures occurring after star fruit intoxication (severe intoxication) is significantly higher than of patients without seizures [13, 17]. Phenytoin, midazolam, diazepam and phenobarbital seem to have little or no effect on the control of persistent seizures provoked by star fruit toxicity. However, significant clinical improvement of seizure was demonstrated in one patient after the use of profofol [20]. 

Seven patients who were in supportive treatment (without need for dialysis) at the time of star fruit ingestion had rruld intoxication presenting hiccups or diarrhea. Six patients improved without dialysis. Time to improve was up to 24 hours in 4 patients, 5 days in another one, and there is no information in one patient. One patient improved after IPD (intermittent peritoneal dialysis) [13,14]. Peritoneal dialysis was not an efficient method of treatment although 1 patient with signs and symptoms of moderate intoxication and 2 with mild intoxication changed from CAPD to IPD (intermittent peritoneal dialysis) and improved [13]. Two patients that remained in CAPD also improved [7, 12]. In one case [13] patient presented diplopia that continued for 6 weeks after improvement of the acute intoxication episode. Patients with severe intoxication did not benefit from peritoneal dialysis treatment [13]. 

Hemoperfusion was used for the first time as an option of treatment in a severe case by Chen LL et al [18] and patient consciousness returned to normal without subsequent mental confusion. Wu MY et al [19] submitted 2 patients with severe intoxication to 20 hours and 8 hours of hemoperfusion and also had good and fast improvement of the intoxication condition. In this 3 cases, 2 hemodialysis sessions in the first described patient, 1 hemodialysis session and 2 daily hemodialysis session in the patients of the second report failed to counterbalance neurotoxicity however consciousness improved dramatically after hemoperfusion [19]. A dramatic decrease in comatose time and rapid weaning from the ventilator may help reduce morbidity and mortality [19]. Hemoperfusion seems to be a promising kind of treatment to severe cases of star fruit intoxication. However this issue requires further analysis with large trials [19]. 

Fang HC et al [24] in their report intended to establish a connection between star fruit and acute oxalate nephropathy. They administered star fruit juice, 4 mL/100 g of body weight, in male Sprague-Dawley rats of 180 to 200 g, with an oxalate concentration of 2.4g/dL, approximately 1 g/kg. The authors established a strong relationship between star fruit and acute oxalate nephropathy. This relationship was found only in the experimental group under both fasting and water deprivation conditions. 

Although there are not many other cases of star fruit oxalate nephrotoxicity described, it seems reasonable to avoid consumption of large amounts of star fruit juice especially on an empty stomach and chronic consumption in patients with underlying chronic renal disease. 

Despite the recent reports of neurotoxicity of star fruit in uremic patients, the first one on star fruit toxicity was described by Muir and Lam [27] in 1980. They related toxic effects of star fruit extract after its intraperitoneal administration in mice. This extract induced seizures and death. In 1993, Martin LC et al. reported the outcome of intractable hiccups in uremic patients associated to star fruit consume [3]. However, the first report of neurotoxicity in human beings was performed by Moyses-Neto M et al (4). Subsequently, many similar case reports were described, but only in 2002 an etiological agent was proposed oxalic acid would be the star fruit neurotoxin [28]. 

Figure 2. Examples of chemical constituents presenting on star fruit juice.

When behavioral recordings are coupled with electroencephalography, in a digital format, the so-called Video-EEG, allows to prove, in freely moving animals, the behavioral and EEG effects after star fruit ingestion or after local apphcation in specific brain regions of either, the crude or the purified toxin. In the first case the hypothesis that experimentally uremic animals, induced by HgCl, a known model of renal failure [48], will reproduce the star fruit intoxication effects found in the patients can be tested (see above). In the second case, the hypothesis that the crude or purified toxin per se will be able to induce behavioral and EEG activity compatible with brain hyperexcitability, possibly associated to seizures is tested. As a positive effect, the latter experimental protocol (with not relationships with renal alterations) will even validate the potential of this neurotoxin as a new tool in the neuroscience field. 

A preliminary characterization of the video-EEG after crude star fruit juice had been given to animals... 

Star fruit juice also induced seizures when applied to cortical areas, showing that convulsant activity is present in crude star fruit extracts. The present data confirm the excitatory profile of AcTx and star fruit extracts. The progressive and sustained EEG epileptiform activity induced by AcTx is a characteristic of known... 

In fhe case of patienfs, fhe only reporf in which the authors claim that star fruit intoxication induce brain lesions (in this case thalamic and cortical) is the one from Chan YL ef al [11]. Unfortimafely fhere is no neurological follow up of fhe evenfual neurological sequelae thaf patienfs who survive will display in fheir future hves after the treatment s rescue. 

It is interesting to notice that the characterization of the cellular and molecular mechanisms of the star fruit intoxication needs to pass through a group of different experimental protocols among them in vivo and the in vitro bioassays. The correlation between in vivo and in vitro models is then more complex that we should think it is [53]. Thus, the particular case of synaptosomes and GABA and glutamate release and re-uptake, shows neurochemical dynamics associated to star fruit intoxication mechanisms in a preparation which consists of isolated synaptic terminals (44). However, additional studies are needed with brain slices from control brains treated with the AcTx and even the use of ex vivo models in vitro bioassays from tissue after in vivo experiments), for example, in our case, brain slices from treated animals. 

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