ArticlePDF Available

Vitamin E as a novel therapy in the treatment of acute aluminum phosphide poisoning

Authors:
  • Tehran University of Medical Sciences (TUMS)

Abstract and Figures

Background/aim: Aluminum phosphide (AlP) is commonly used as a fumigant in developing countries. Induction of oxidative stress is one of the most important mechanisms of its toxicity. In this regard, and considering that there is no specific antidote for its treatment, the aim of this study was to evaluate the effect of vitamin E in the treatment of acute AlP poisoning. Materials and methods: This was a clinical trial on acute AlP poisoned patients. All patients received supportive treatment. In addition, the treatment group received vitamin E (400 mg/BD/IM). Level of malondialdehyde (MDA) and total antioxidant capacity of plasma were measured. Results: There was no significant difference between the treatment and control groups with regard to demographic, clinical, or paraclinical data or Simplified Acute Physiology Score II (SAPSII) on admission. Systolic blood pressure significantly increased during the first 24 h in the treatment group (P < 0.05). The plasma MDA level significantly decreased in the treatment group (P < 0.05). Vitamin E administration decreased the necessity (30% vs. 62%, P < 0.05) and duration of intubation and mechanical ventilation (P < 0.05). It significantly reduced the mortality rate in the treatment group compared to the control group (15% vs. 50%, respectively, P < 0.05). Conclusion: Vitamin E along with supportive treatment could have a therapeutic effect in acute AlP poisoning.
Content may be subject to copyright.
795
http://journals.tubitak.gov.tr/medical/
Turkish Journal of Medical Sciences
Turk J Med Sci
(2017) 47: 795-800
© TÜBİTAK
doi:10.3906/sag-1512-6
Vitamin E as a novel therapy in the treatment of acute aluminum phosphide poisoning
Zahra HALVAEI1, Hiva TEHRANI1, Kambiz SOLTANINEJAD2, Mohammad ABDOLLAHI3,4, Shahin SHADNIA5,*
1Faculty of Pharmacy, Islamic Azad University of Medical Sciences, Tehran, Iran
2Department of Forensic Toxicology, Legal Medicine Research Center, Legal Medicine Organization, Tehran, Iran
3Department of Toxicology and Pharmaceutical, Faculty of Pharmacy, and Pharmaceutical Sciences Research Center,
Tehran University of Medical Sciences, Tehran, Iran
4Toxicological and Diseases Group, Pharmaceutical Sciences Research Group, Tehran Unviversity of Medical Sciences, Tehran, Iran
5Toxicological Research Center, Excellent Center of Clinical Toxicology, Department of Clinical Toxicology, Loghman Hakim Hospital
Poison Center, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
* Correspondence: shahin1380@yahoo.com
1. Introduction
Aluminum phosphide (AlP) is used widely throughout
the world as a pesticide and fumigant because of
its ecacy and low cost (1). AlP is one of the most
frequently reported causes of acute chemical poisoning
in Asia (2–4). In Iran, it is available in 3-g tablets
containing 1 g of AlP and known as “rice tablet”; it
causes acute poisoning with a high mortality rate (5–7).
AlP toxicity is due to liberating phosphine (PH3) gas
aer its reaction with moisture, water, or hydrochloric
acid in the stomach (8,9). e major of mortality occurs
during the rst 12–24 h aer exposure and is mostly
due to cardiovascular and respiratory involvement
(8,9).
e exact mechanism of phosphine toxicity is not
clear and some mechanisms are reported (8,9). Previous
studies suggested that the induction of oxidative stress
has the main role in AlP toxicity (10,11), which is
emphasized by recent studies (12–15).
As there is no specic antidote for acute AlP poisoning,
its treatment is mainly supportive and symptomatic
(1,8,9). By considering the induction of oxidative stress as
the main mechanism of AlP toxicity and with regard to
the role of vitamin E in the enzymatic antioxidants defense
and function as a free radical scavenger (16–18), its use
may have a therapeutic eect in the treatment of AlP-
poisoned patients.
e aim of the present study was to investigate the
therapeutic eects of vitamin E in acute human AlP
poisoning.
2. Materials and methods
2.1. Patients
is was a prospective, randomized, control open label
trial on acute AlP intoxicated patients that were treated in
the intensive care unit (ICU) over a 1-year period.
Acute AlP-intoxicated patients above the age of 12
years who were admitted during the rst 6 h aer exposure
Background/aim: Aluminum phosphide (AlP) is commonly used as a fumigant in developing countries. Induction of oxidative stress is
one of the most important mechanisms of its toxicity. In this regard, and considering that there is no specic antidote for its treatment,
the aim of this study was to evaluate the eect of vitamin E in the treatment of acute AlP poisoning.
Materials and methods: is was a clinical trial on acute AlP poisoned patients. All patients received supportive treatment. In addition,
the treatment group received vitamin E (400 mg/BD/IM). Level of malondialdehyde (MDA) and total antioxidant capacity of plasma
were measured.
Results: ere was no signicant dierence between the treatment and control groups with regard to demographic, clinical, or
paraclinical data or Simplied Acute Physiology Score II (SAPSII) on admission. Systolic blood pressure signicantly increased during
the rst 24 h in the treatment group (P < 0.05). e plasma MDA level signicantly decreased in the treatment group (P < 0.05). Vitamin
E administration decreased the necessity (30% vs. 62%, P < 0.05) and duration of intubation and mechanical ventilation (P < 0.05). It
signicantly reduced the mortality rate in the treatment group compared to the control group (15% vs. 50%, respectively, P < 0.05).
Conclusion: Vitamin E along with supportive treatment could have a therapeutic eect in acute AlP poisoning.
Key words: Aluminum phosphide, oxidative stress, poisoning, vitamin E
Received: 03.12.2015 Accepted/Published Online: 22.01.2017 Final Version: 12.06.2017
Research Article
796
HALVAEI et al. / Turk J Med Sci
with no advanced medical management for AlP poisoning
in any medical center before admission were included in
this study. e exclusion criteria were history of diabetes
mellitus, cardiovascular, respiratory, renal, and hepatic
failure, substance abuse, and co-ingestion.
e diagnosis was conrmed based on history of
exposure, clinical manifestations, laboratory ndings,
and other circumstantial evidence such as availability of a
poison bottle or a label. In fatal cases, toxicological analysis
and a histopathological examination were performed.
A positive silver nitrate test for PH3 gas on stomach
contents and tissues along with the liver postmortem
histopathological ndings conrmed the AlP poisoning.
According to the mentioned criteria, 36 patients were
included in the study consecutively. Each patient with an
even le number was included in the vitamin E treatment
group (n = 20) and the patients with odd le numbers were
included in the control group (n = 16).
2.2. Study design and treatments
All the patients received gastric decontamination with
sodium bicarbonate (44 mEq), permanganate potassium
(1:10,000), and activated charcoal (1 g/kg) in the rst
6 h aer exposure. All the patients were admitted to the
ICU, as they needed intubation, mechanical ventilation,
and intensive monitoring. ey were treated with the
same protocol (magnesium sulfate 4–6 g by IV infusion
daily, calcium gluconate 4 g by IV infusion daily,
adequate hydration, and norepinephrine 10 µg/min as
vasopressor) under the supervision of the same physicians
and nurses. e described treatments were based on the
clinical toxicology department protocols. In the vitamin
E treatment group, vitamin E (as DL-alpha tocopheryl
acetate, 100 IU/mL, OSVAH Pharmaceutical Co. Tehran,
Iran; 400 mg/IM, every 12 h) was administered up to 72 h.
We followed the patients up to discharge from the hospital
or death.
e protocol of the study was approved by the ethical
committee of Shahid Beheshti University of Medical
Sciences, Tehran, Iran.
2.3. Sampling and bioanalysis
Blood sampling was performed at the admission on
hospital and repeated each 24 h up to 72 h of hospitalization
in the ICU. Venous blood samples (5 mL) were collected in
dierent heparinized tubes and then plasma samples were
separated via centrifugation at 3500 rpm for 10 min and
frozen at –80 °C. On average, the time interval between
sampling and analysis was 1 week. Lipid peroxidation in the
plasma in two groups was evaluated by the thiobarbituric
acid reactive substances (TBARS) method (19). First
250 µL of 20% trichloroacetic acid (TCA) in 10 mL of
sodium sulfate (2 M) was added to 0.5 mL of plasma. Aer
precipitation of the protein with TCA, washing with 300
µL of sulfuric acid (0.05 M) was performed. en 300 µL of
thiobarbituric acid (TBA) (0.67% w/v) solution was added
to the mixture. e mixture was incubated in a boiling
water bath for 30 min. Aer cooling, the samples were
extracted with n-butanol and centrifuged at 3500 rpm.
e absorbance was read at 530 nm by ELISA microplate
reader (Synergy, BioTech Instruments Inc, Germany).
1,1,3,3-Tetramethoxy propane was used for drawing the
calibration curve. Malondialdehyde (MDA) was expressed
as micromoles of MDA per liter of plasma.
e total antioxidant capacity (TAC) of plasma was
evaluated using the ferric reducing ability of plasma
(FRAP) assay (20). Ferric tripyridyltirazine (Fe3+-TPTZ)
complex is reduced to the blue color marker ferrous (Fe2+)
form at acidic pH. To 50 µL of plasma was added 1500
µL of freshly prepared FRAP reagent [25 mL of acetate
buer (pH = 3.6, 300 mmol/L), 2.5 mL of FeCl3, 6H2O
(20 mmol/L), 2.5 mL of TPTZ (10 mmol/L TPTZ in 40
mmol/L HCl)]. Aer 15 min incubation at 37 °C in a water
bath, absorbance was determined by ELISA microplate
reader (Synergy, BioTech Instruments Inc, Germany) at
593 nm. en samples were placed at 37 °C in the water
bath and absorption was measured aer 4 min. FRAP
values were measured by calculation of the absorbance
change in plasma sample compared with that of trolox
standard (20).
2.4. Data collection and statistical analysis
We collected patients’ information regarding sex, age, cause
of poisoning, number of ingested AlP tablets, time interval
between exposure and beginning of treatment, route of
exposure, clinical and laboratory ndings at admission
and during the rst 24 h of hospitalization, duration of
hospitalization, and outcome and prepared qualifying case
records. All data were kept condential during the study.
e Glasgow Coma Scale (GCS) and Simplied Acute
Physiology Score II (SAPSII) were calculated at admission
(21,22). All data were analyzed with SPSS version 12. Data
were expressed as mean ± SD for quantitative variables
and as frequency and percentage for qualitative variables.
e chi-square test was used for statistical comparison
of qualitative variables. e normal distribution of
quantitative variables was tested by Kolmogorov–
Smirnov test. e Mann–Whitney U-test was used for
nonparametric variables and the independent Student’s
t-test was used for parametric variables. P values of 0.05 or
less were considered statistically signicant.
3. Results
In the present study, 36 patients (13 men, 23 women) with
acute AlP poisoning were included, of whom 20 (5 men,
15 women) were in the treatment group and 16 (8 men, 8
women) were controls. e route of exposure was deliberate
ingestion in all patients. e main clinical manifestation
was vomiting, observed in the most of the patients in the
treatment and control groups (90% vs. 87.5%, respectively).
Table 1 summarizes the demographic, clinical, and
797
HALVAEI et al. / Turk J Med Sci
Table 1. Distribution of the AlP intoxicated patients according to demographic, clinical, and paraclinical characteristics at admission.
Parameter (normal range, unit) All patients (n = 36)
(%) Mean ± SD (range)
Treatment group (n = 20)
(%) Mean ± SD (range)
Control group (n = 16)
(%) Mean ± SD (range) P-value
Sex Male 13 (26) 5 (25) 8 (50) 0.17
Female 23 (64) 15 (75) 8 (50)
Age (years) 25.56 ± 8.37 (14–50) 24.95 ± 8.11 (15–44) 26.31 ± 8.90 (14–50) 0.46
Number of AlP tablets 1.40 ± 0.86 (0.25–4) 1.28 ± 0.75 (0.25–3) 1.57 ± 1 (0.5–4) 0.48
TBOPAH$ (min) 87.50 ± 64.36 (15–300) 98.25 ± 76.66 (15–300) 74.06 ± 43.29 (15–180) 0.52
Level of consciousness consciousness 20 (56) 11 (55) 9 (56) 1
unconsciousness 16 (44) 9 (45) 7 (44)
Systolic blood pressure (≤120 mmHg) 89.46 ± 15.76 (56–130) 89.16 ± 17.95 (56–130) 89.81 ± 13.29 (60–110) 0.90
Diastolic blood pressure (≤80 mmHg) 57.79 ± 11.06 (37–80) 55.76 ± 11.03 (37–80) 60.67 ± 10.91 (40–70) 0.25
Pulse rate (60–100 beats/min) 92.46 ± 15.94 (65–130) 90.50 ± 16.68 (65–130) 95.07 ± 15.04 (70–122) 0.41
Respiratory rate (16–24 breaths/min) 19.25 ± 4.08 (12–30) 19.95 ± 4.16 (14–30) 18.38 ± 3.93 (12–26) 0.32
Electrocardiogram Normal 20 (56) 13 (65) 7 (44) 0.31
Abnormal 16 (44) 7 (35) 9 (56)
pH (7.35–7.45) 7.39 ± 0.08 (7.22–7.49) 7.40 ± 0.07 (7.24 ± 7.48) 7.38 ± 0.09 (7.22–7.49) 0.50
PCO2 (35–45 mmHg) 30.03 ± 7.35 (16.90–43.10) 31.81 ± 7.06 (16.90–42.20) 27.81 ± 7.30 (18.10–43.10) 0.11
Serum HCO3 (22–26 mEq/L) 18.64 ± 5.15 (9–29.1) 20.06 ± 5.47 (9.90–29.10) 16.88 ± 4.24 (9–24.5) 0.06
Blood glucose (70–110 mg/dL) 148.75 ± 55.73 (74–282) 125.25 ± 48 (74–242) 178.13 ± 51.70 (101–282) 0.003**
Blood urea nitrogen (7–18 mg/dL) 27.25 ± 11.61 (12–60) 29.45 ± 12.85 (12–60) 24.50 ± 9.51 (12–40) 0.20
Creatinine (0.6–1.2 mg/dL) 0.94 ± 0.21 (0.60–1.40) 0.91 ± 0.21 (0.70–1.40) 1 ± 0.21 (0.60–1.30) 0.20
Sodium (135–145 mEq/L) 143.94 ± 5.07 (135–156) 143.40 ± 4.89 (137–155) 144.67 ± 5.38 (135–156) 0.48
Potassium (3.5–5 mEq/L) 3.94 ± 0.46 (3–5.10) 3.86 ± 0.41 (3–4.60) 4.05 ± 0.53 (3.20–5.10) 0.52
Calcium (8.4–10.2 mg/dL) 8.82 ± 0.79 (7.50–10.50) 8.74 ± 0.86 (7.50–10.40) 8.91 ± 0.72 (8–10.50) 0.55
Magnesium (1.9–2.5 mg/dL) 2.18 ± 0.58 (1.40–4) 2.08 ± 0.58 (1.40–4) 2.41 ± 0.56 (1.90–3.50) 0.07
White blood cell count (7–10 × 1000/µL) 15.55 ± 22.61 (3.20–141) 17.47 ± 29.42 (3.20–141) 12.81 ± 4.35 (5.80–20.60) 0.44
Hematocrit (35–45%) 38.53 ± 5.58 (27.50–48.10) 37.04 ± 6.05 (27.50–48.10) 40.65 ± 4.16 (32–46.60) 0.06
Platelet (150–450 × 1000/µL) 268.76 ± 110.01 (95–609) 289.85 ± 122.86 (95–609) 238.64 ± 83.68 (101–374) 0.19
Serum total protein (6.6–8.8 g/dL) 6.35 ± 0.78 (5.10–8.20) 6.54 ± 0.80 (5.10–8.20) 5.92 ± 0.58 (5.10–7.00) 0.08
Albumin (3.5–5.3 g/dL) 4.00 ± 0.64 (3.10–5.10) 4.16 ± 0.63 (3.20–5.10) 3.71 ± 0.60 (3.10–4.60) 0.15
Aspartate transaminase (up to 37 U/L) 26.48 ± 14.96 (10–64) 28 ± 15.53 (10–64) 24.38 ± 14.47 (11–62) 0.44
Alanine transaminase (up to 41 U/L) 49.96 ± 75.35 (5–298) 46.11 ± 61.91 (12–242) 55.30 ± 93.34 (5–298) 0.31
Alkaline phosphatase (80–306 U/L) 157.54 ± 37.53 (95–233) 143.38 ± 32.08 (95–187) 178 ± 36.83 (113–233) 0.03*
Total bilirubin (0.1–1.2 mg/dL) 1.2 ± 0.52 (0.50–2.70) 1.17 ± 0.61 (0.50–2.70) 1.23 ± 0.37 (0.60–1.90) 0.29
Lactate dehydrogenase (up to 513 U/L) 457.32 ± 135.85 (279–752) 445.45 ± 131.81 (298–740) 474.28 ± 144.66 (279–752) 0.55
Creatine phosphokinase (24–195 U/L) 170.18 ± 64.69 (53–305) 190.15 ± 59.74 (56–305) 139.46 ± 61.84 (53–295) 0.03*
$ Time between onset of poisoning and admission to hospital, SD = Standard deviation
* e dierence between the two groups is signicant at P < 0.05
** e dierence between the two groups is signicant at P < 0.005
Chi-square test was used for statistical analysis
Mann–Whitney U-test was used for statistical analysis
t-test was used for statistical analysis
798
HALVAEI et al. / Turk J Med Sci
laboratory results. SAPSII was determined in the treatment
(4.7 ± 2) and control groups (5.05 ± 3.13). e results
showed no signicant dierence (P = 0.68).
Systolic blood pressure (SBP) signicantly increased
during the rst 24 h in the treatment group (89.16 ± 17.95
mmHg at admission vs. 98.95 ± 15.45 mmHg 24 h aer
onset of poisoning, P < 0.05). e results also showed that
there was no signicant dierence between the two groups
due to SBP 24 h aer the onset of poisoning (98.95 ± 15.45
mmHg in the treatment group vs. 89.21 ± 20.25 mmHg in
the control group, P = 0.13).
We observed signicant increases in diastolic blood
pressure (DBP) in the treatment group (55.76 ± 11.03
mmHg at admission vs. 60.63 ± 13.58 mmHg 24 h aer the
onset of poisoning, P < 0.05) and signicant decreases in
DBP in the control group (60.67 ± 10.91 mmHg at admission
vs. 50.43 ± 12 mmHg 24 h aer the onset of poisoning,
P < 0.05). e data showed a signicant dierence between
the two groups with regard to DBP 24 h aer the onset of
poisoning (P < 0.05).
e results showed a signicant dierence in blood
pH between the treatment and control groups (7.43 ± 0.04
vs. 7.33 ± 0.1, P < 0.001) 24 h aer onset of poisoning.
In addition, there was no signicant dierence between
the two groups due to PCO2 (36.24 ± 7.57 mmHg in the
treatment group vs. 34.19 ± 6.91 mmHg in the control
group, P = 0.4). We observed a signicant dierence in
serum bicarbonate between the two groups 24 h aer the
onset of poisoning (24.22 ± 6.55 mEq/L in the treatment
group vs. 18.91 ± 5.62 mEq/L in the control group, P <
0.05).
ere was no signicant dierence in the TAC of
plasma in the treatment and control groups at admission
(Table 2). Twenty-four hours aer the onset of poisoning,
the TAC of plasma in the control group was signicantly
higher than that in the treatment group (Table 2).
At admission, the plasma MDA level was not signicantly
dierent between the treatment and control groups. e
plasma MDA level signicantly decreased in the treatment
group and it signicantly increased in the control group. e
plasma MDA level in the treatment group was signicantly
lower than that in the control group 24 h aer the onset of
poisoning (Table 2).
e percentage of patients who required intubation
and mechanical ventilation was signicantly lower in the
treatment group than in the control group (30% vs. 62%, P <
0.05). In addition, the duration of intubation and mechanical
ventilation in the treatment group was signicantly
lower compared to the control group. e total dose of
norepinephrine was not signicantly dierent between the
two groups (Table 3).
Although the duration of hospitalization was not
signicantly dierent between the two groups (Table 3), the
results showed that most of the fatality occurred during the
rst 12 h aer admission in the control group, and in the
treatment group most of the fatality was observed 20 h aer
admission (Figure). In addition, the data showed that the
mortality rate was signicantly lower in the treatment group
than in the control group (15% vs. 50%, P = 0.02).
4. Discussion
AlP poisoning is a major health problem with a high mortality
rate in Iran and other countries (2–4,6). Unfortunately, to
date, there is not a specic antidote for treatment of this type
of fatal poisoning and the only therapeutic measures are
supportive and symptomatic (9). In this regard, performing
studies that evaluate other therapeutic protocols is necessary.
ere are many suggested mechanisms for AlP poisoning.
One of the most important mechanisms is involvement
of oxidative stress (10–14). From this viewpoint, the
antioxidants may have a therapeutic role in the treatment of
AlP poisoning (10,12).
Table 2. Comparison of plasma TAC and MDA levels at admission and 24 h aer the onset of
poisoning in the treatment and control groups.
Parameters Group At admission
Mean ± SD
24 h aer onset of
poisoning Mean ± SD P-value
MDA (µmol/L) Treatment 130.91 ± 14.11124.88 ± 8.230.02*
Control 142.45 ± 29.28 151.51 ± 37.34 0.04*
TAC (mmol/L) Treatment 11.57 ± 6.0510.45 ± 3.480.23
Control 12.79 ± 3.63 13.26 ± 4.02 0.57
* e dierence between two groups is signicant at P < 0.05
ere is no signicant dierence between the treatment and control groups at admission
ere is a signicant dierence between the treatment and control groups 24 h aer the onset of
poisoning at P < 0.05
Mann–Whitney U-test was used for all the statistical analysis
799
HALVAEI et al. / Turk J Med Sci
Previous studies showed that vitamin E had a protective
role in the in vivo or in vitro toxicity of some poisons
through its antioxidant activity and lowering cell death
by decreased the levels of MDA, reactive oxygen species
production, and lipid peroxidation (18,23–25).
In the present study, we aimed to evaluate the ecacy
of intramuscular administration of vitamin E as an
antioxidant agent in patients with acute AlP poisoning.
e results showed signicant rises in SBP and DBP
in the treatment group 24 h aer the onset of poisoning,
which could be due to the role of vitamin E in reduction of
myocardial and vessels injury through the decrease in lipid
peroxidation (26,27).
e results in the control group showed progressive
metabolic acidosis during the rst 24 h aer the onset of
poisoning, which could be due to tissue hypoperfusion.
In the present study, the TAC and MDA levels at
admission showed no signicant dierence between the
two groups. In addition, the results showed that the serum
levels of MDA were signicantly decreased aer 24 h in
the treatment group, while in the control group they were
signicantly increased. ese results are in concordance of
our previous study, in which the administration of N-acetyl
cysteine as an antioxidant resulted in similar ndings (12).
Vitamin E administration decreased the necessity for
intubation and mechanical ventilation and was associated
with a decrease in duration of intubation and mechanical
ventilation. is result was similar to that of our previous
study (12). Although in the previous studies mortality
rates of 60%–80% were reported in the AlP poisoning
cases with conventional supportive and symptomatic
treatment (7,28,29), in the present study administration of
vitamin E signicantly reduced the mortality rate in the
treatment group compared to the control group (15% vs.
50%, respectively).
In conclusion, the present study showed that the
administration of vitamin E along with supportive
treatment decreased the mortality rate and so it could
be considered in the treatment of acute AlP poisoning in
combination with other therapeutic protocols.
e limitations of this study were small sample size and
lack of blinding in the study design.
Acknowledgment
is study was supported by a grant from the Toxicological
Research Center of Shahid Beheshti University of Medical
Sciences Tehran, Iran (Grant number: 90-M.T-12-306).
Table 3. Comparison of treatment and control groups according to duration of intubation, ventilation, hospitalization,
and dose of vasopressor
Parameters Treatment group (n = 20)
Mean ± SD (range)
Control group (n = 16)
Mean ± SD (range) P-value
Duration of intubation and ventilation (h) 4.15 ± 9 (0–32) 18.36 ± 28.37 (0–85.5) 0.04*
Total dose of norepinephrine (mg) 10.34 ± 14.35 (0–50.40) 10.15 ± 12.79 (0–43.20) 0.42
Duration of hospitalization (h) 69.09 ± 35.19 (21–159) 62.53 ± 68.87 (3.25–229) 0.16
*e dierence between the two groups is signicant at P < 0.05
t-test was used for all the statistical analysis
0
1
2
3
4
2-6 6-12 12-18 18-24 24-30 30-36
Duration of hospitalization in nonsurvivors
(h)
Number of fatal cases
Control group
Treatment group
Figure. Comparison of the duration of hospitalization between
nonsurvivors in the treatment and control groups.
800
HALVAEI et al. / Turk J Med Sci
References
1. Moghadamnia AA. An update on toxicology of aluminum
phosphide. DARU 2012; 20: 25. doi:10.1186/2008-2231-20-25.
2. Sharma AD, Gupta V, Kaushik JS, Mittal K. Aluminum
phosphide (Celphos) poisoning in children: a 5-year experience
in a tertiary care hospital from northern India. Indian J Crit
Care Med 2014; 18: 33-36.
3. Anand R, Binukumar BK, Gill KD. Aluminum phosphide
poisoning: an unsolved riddle. J Appl Toxicol 2011; 31: 499-
505.
4. Shadnia S, Sasanian G, Allami P, Hosseini A, Ranjbar A,
Amini-shirazi N, Abdollahi M. A retrospective 7-years study
of aluminum phosphide poisoning in Tehran: opportunities
for prevention. Hum Exp Toxicol 2009; 28: 209-213.
5. Mehrpour O, Singh S. Rice tablet poisoning: a major concern
in Iranian population. Hum Exp Toxicol 2010; 29: 701-702.
6. Soltaninejad K, Nelson LS, Bahreini SA, Shadnia S. Fatal
aluminum phosphide poisoning in Tehran-Iran from 2007 to
2010. Indian J Med Sci 2012; 66: 66-70.
7. Shadnia S, Mehrpour O, Soltaninejad K. A simplied acute
physiology score in the prediction of acute aluminum
phosphide poisoning outcome. Indian J Med Sci 2010; 64: 532-
539.
8. Bumbrah GS, Krishan K, Kanchan T, Sharma M, Sodhi GS.
Phosphide poisoning: a review of literature. Forensic Sci Int
2012; 214: 1-6. doi:10.1016/j.forsciint. 2011.06.018.
9. Proudfoot AT. Aluminium and zinc phosphide poisoning. Clin
Toxicol (Phila) 2009; 47: 89-100.
10. Hsu CH, Chi BC, Casida JE. Melatonin reduces phosphine-
induced lipid and DNA oxidation in vitro and in vivo in rat
brain. J Pineal Res 2002; 32: 53-58.
11. Hsu CH, Chi BC, Liu MY, Li JH, Chen CJ, Chen RY. Phosphine-
induced oxidative damage in rats: role of glutathione.
Toxicology 2002; 179: 1-8.
12. Tehrani H, Halvaie Z, Shadnia S, Soltaninejad K, Abdollahi M.
Protective eects of N-acetylcysteine on aluminum phosphide-
induced oxidative stress in acute human poisoning. Clin
Toxicol (Phila) 2013; 51: 23-28.
13. Kariman H, Heydari K, Fakhri M, Shahrami A, Arhami
Dolatabadi A, Mohammadi HA, Gharibi M. Aluminium
phosphide poisoning and oxidative stress: serum biomarker
assessment. J Med Toxicol 2012; 8: 281-284.
14. Anand R, Sharma DR, Verma D, Bhalla A, Gill KD, Singh S.
Mitochondrial electron transport chain complexes, catalase
and markers of oxidative stress in platelets of patients with
severe aluminum phosphide poisoning. Hum Exp Toxicol
2013; 32: 807-816.
15. Anand R, Kumari P, Kaushal A, Bal A, Wani WY, Sunkaria A,
Dua R, Singh S, Bhalla A, Gill KD. Eect of acute aluminum
phosphide exposure on rats - a biochemical and histological
correlation. Toxicol Lett 2012; 215: 62-69.
16. Singh M, Sandhir R, Kiran R. Eects on antioxidant status of
liver following atrazine exposure and its attenuation by vitamin
E. Exp Toxicol Pathol 2011; 63: 269-276.
17. Singh M, Sandhir R, Kiran R. Oxidative stress induced by
atrazine in rat erythrocytes: mitigating eect of vitamin E.
Toxicol Mech Methods 2010; 20: 119-126.
18. Shadnia S, Dasgar M, Taghikhani S, Mohammadirad A,
Khorasani R, Abdollahi M. Protective eects of α-tocopherol
and N-acetyl-cysteine on diazinon-induced oxidative stress
and acetylcholinesterase inhibition in rats. Toxicol Mech
Methods 2007; 17: 109-115.
19. Satih K. Serum lipid peroxide in cerebrovascular disorders
determined by a new calorimetric method. Clin Chim Acta
1978; 90: 37-43.
20. Benzie IE, Strain JJ. e ferric reducing ability of plasma
(FRAP) as a measure of “antioxidant power”: the FRAP assay.
Anal Biochem 1996; 239: 70-76.
21. Teasdale G, Jennett B. Assessment of coma and impaired
consciousness: a practical scale. Lancet 1974; 2: 81-84.
22. Le Gall JR, Lemeshow S, Saulnier F. A new Simplied Acute
Physiology Score (SAPS II) based on a European/North
American multicenter study. JAMA 1993; 270: 2957-2963.
23. Wiser J, Alexis NE, Jiang Q, Wu W, Robinette C, Roubey R,
Peden DB. In vivo gamma-tocopherol supplementation
decreases systemic oxidative stress and cytokine responses
of human monocytes in normal and asthmatic subjects. Free
Radic Biol Med 2008; 45: 40-49.
24. Soltaninejad K, Abdollahi M. Current opinion on the science
of organophosphate pesticides and toxic stress: a systematic
review. Med Sci Monit 2009; 15: RA75-90.
25. Ozden S, Catalgol B, Gezginci-Oktayoglu S, Arda-Pirincci
P, Bolkent S, Alpertunga B. Methiocarb-induced oxidative
damage following subacute exposure and the protective eects
of vitamin E and taurine in rats. Food Chem Toxicol 2009; 47:
1676-1684.
26. Pryor W. Vitamin E and heart disease: basic science to clinical
intervention trials. Free Radic Biol Med 2000; 28: 141-164.
27. Iannitti T, Palmieri B. Antioxidant therapy eectiveness: an up
to date. Eur Rev Med Pharmacol Sci 2009; 13: 245-278.
28. Mehrpour O, Alfred S, Shadnia S, Keyler DE, Soltaninejad K,
Chalaki N, Sedaghat M. Hyperglycemia in acute aluminum
phosphide poisoning as a potential prognostic factor. Hum
Exp Toxicol 2008; 27: 591-595.
29. Hajouji Idrissi M, Oualili L, Abidi K, Abouqal R, Kerkeb O,
Zeggwagh AA. Severity factors of aluminum phosphide
poisoning (Phostoxin). Ann Fr Anesth Reanim 2006; 25: 382-
385.
... In addition to the basic supportive treatment, the physicians are trying to ameliorate AlP toxicity either by reducing phosphine liberation in the stomach or by alleviation of phosphineinduced cellular dysfunction [4,5]. Antioxidants were also tried clinically to alleviate phosphine-induced oxidative stress such as N-acetyl cysteine (NAC) [6], vitamin C [7], vitamin E [8] and coenzyme Q10 [9]. ...
... Considering GIT decontamination, conventional gastric lavage in acute AlP is done using water or saline. Besides, potassium permanganate (KMNO 4 ), charcoal or sodium bicarbonate (NaHCO 3 ) could be added to these aqueous solutions [8,10]. By reviewing recent literature, laboratory experiments demonstrated that AlP is highly water-soluble with an immediate release of phosphine, whereas the AlP tablet preserves its integrity in the oily medium [11]. ...
... In the last few years, the number of AlP fatalities had dramatically increased in agricultural countries in the absence of an effective antidote to the moment. Thus, different researches aimed to ameliorate aluminum phosphide toxicity either through GIT decontamination to decrease the liberated phosphine or counteracting the lethal effects of absorbed phosphine [8,21]. Theoretically, AlP is highly water-soluble and phosphine gas is rapidly liberated upon its presence in aqueous solution. ...
Article
Full-text available
Aluminum phosphide (AlP) poisoning had high morbidities and mortalities with absence of a standardized approach for the treatment. The present study investigated the efficiency of GIT decontamination methods and Coenzyme Q10(Co Q10) (Ubiquinone) in improving the outcome of acute AlP poisoning. A total of 90 patients were included and all patients received immediately supportive measures, then they distributed into three equal groups: In group I, gastric lavage was done using KMNO4 solution (1:10 000); group II received 250–500 ml liquid paraffin oil orally; group III received 300 mg of Co Q10 dissolved in liquid paraffin. Co Q10 was continued in a dose of 200 mg/day every 12 h. Follow-up blood pressure, arterial blood gases, serum troponin level and need for intubation revealed that the best improvement was in group III followed by group II. The percentage of survivors was 76.67% in group III and 70% of the patients had no residual effects. In group II, the survivors were 63.33%, and 36.67% of the cases discharged without sequelae. The survivors in group I constituted 26.67% and only 16.67% of the patients had no residual effects. GIT decontamination with aqueous solutions in acute AlP poisoning should be avoided. Rapid oral intake of any available oil as a prehospital treatment or immediately on hospital admission could critically improve the outcome of acute AlP poisoning. Besides, the addition of Co Q10 to the oil further improve patients’ prognosis.
... [2][3][4] The conventional treatment options include activated charcoal, alkalinization, calcium gluconate, magnesium sulfate, vitamin E, vitamin C, n-acetylcysteine, extracorporeal membrane oxygenation (ECMO), and renal replacement therapy (RRT), if necessary. [2][3][4][5][6][7][8][9] In some cases, however, these treatments are not sufficient to prevent morbidity and mortality. Since our patient's hypotension and resistant metabolic acidosis did not improve with conventional treatment methods and she was clinically poor condition we decided to apply automated red blood cell exchange (ARCE) therapy. ...
... Because oxidative stress was shown to have an important role in AIPP, use of an antioxidant may be beneficial to limit AIP toxicity as a life-saving antidote. Halvaei et al. 8 compared the administration of vitamin E in AIPP compared with a placebo, in which vitamin E administration significantly increased blood pressure and reduced mortality in the treatment group. Furthermore, Tehrani et al. 9 demonstrated the possible protective effects of nacetylcysteine on cardiovascular complications. ...
Article
Full-text available
Aluminum phosphide (AIP) is a fumigant commonly used in agricultural areas. AIP is frequently misused for suicidal purposes because it is easily accessible. AIP poisoning causes severe metabolic acidosis, resistant hypotension, acute respiratory distress syndrome, and multiorgan failure with cardiogenic shock. Despite supportive management and intensive care, most patients die following AIP ingestion because there is no specific antidote. In this case report we present a 15‐year‐old female who presented with vomiting, coma and epigastric pain. She developed resistant metabolic acidosis and hypotension due to AIP poisoning. Although supportive treatment did not result in clinical improvement, she was successfully treated with automated red blood cell exchange. Automated red blood cell exchange is a procedure which is used to exchange the patient erythrocyte mass with donor red blood cell. Although automated red blood cell exchange is a preferred treatment method in the complications of sickle cell anemia, some blood diseases and infectious diseases such as malaria and babesiosis, there is little information about its use in poisoning. To the best of our knowledge, this is the first child with AIP poisoning who was treated with automated red blood cell exchange.
... This result in agreement with Kariman et al. (2012) and Mehrpour et al. (2012) who found decrease in TAC in ALP studied patients. Several experimental studies reported that ALP could cause oxidative stress by production of oxygen free radicles, lipid peroxidation and impairment of mitochondrial electron transport chain resulting in decrease in TAC (Hsu et al., 2002Nath et al., 2011and Baghaei et al., 2016).These studies were supported with another study done by Halvaei et al. (2017) who reported that there was decrease in TAC after ALP exposure indicating oxidative stress which was improved after administration of vitamin E as an antioxidant. ...
... Kariman et al. (2012) reported that ALP toxicity induced an oxidative stress with decreased TAC (1.91 ± 0.18 mmol/ml) and stated that phosphine induced oxidative damage was associated with mortality but no cut off point was determined in their study. On the other hand, Halvaei et al. (2017) found no difference in the value of TAC between control and treatment group with antioxidant after ALP exposure. ...
... A 21-year-old male who ingested a 3-g AlP tablet, was successfully treated with a combination of routine approaches and administration of antioxidants such as vitamin C (1000 mg every 12 h via slow IV infusion), vitamin E (400 Units, IM) and NAC (140 mg/kg oral as a loading dose followed by 70 mg/kg oral every 4 h, for up to 17 doses) [52]. Administered at 400 mg BD by intramuscular (IM) route besides other supportive treatments to AlP-poisoned subjects, vitamin E was able to decrease the requirement (30 vs. 62%) and duration of mechanical ventilation and reduce the mortality rate (15% vs. 50%), as compared to controls [53]. ...
... Even at high doses, NAC was well-tolerated without causing side effects and actually reduced AlP-induced mortality rate [50]. Vitamin E decreased the fatality rate [53] and exerted more marked effects when co-administered with NAC [52]. T3 [54], vasopressin [54] and ALCAR [63] were suggested to improve AlP-related alterations in cardiovascular function, ATP levels and apoptosis. ...
... When AlP comes in contact with water or gastric HCL, phosphine (PH3) gas is liberated and is rapidly absorbed. Several mechanisms of toxicity are proposed, with the primary one being mitochondrial dysfunction related to the inhibition of oxidative phosphorylation by PH3, thereby reducing the formation of ATP and producing reactive oxygen species (ROS) [5,6]. In addition, PH3 inhibits the detoxifying enzymes catalase and peroxidase resulting in oxidative stress, lipid peroxidation, and DNA damage [7]. ...
Article
Introduction: Cardiotoxicity represents the primary cause of death in acute aluminum phosphide (AlP) poisoning. Prompt supportive care can improve patient survival. This study assessed the role of echocardiography in estimating the survival probability of AlP-poisoned patients admitted to the intensive care unit. Methods: A prospective cohort study of symptomatic acute AlP poisoned patients was conducted between September 2019 and December 2020. Patients were subjected to history taking, clinical examination, To be included, patient evaluation needed to include electrocardiographic (ECG) and echocardiographic studies. The statistical analysis assessed the association between patient survival and relevant factors. Survival analysis was performed using the Kaplan-Meier survival curve and Cox proportional hazard regression. Results: A total of 90 patients met inclusion criteria. Electrocardiographic abnormalities were detected in 38.1% of survivors and 82.6% of non-survivors (p < 0.001). Survivors had a higher mean left ventricle ejection fraction (LVEF) (50.86 ± 6.30% vs. 26.52 ± 7.64%, respectively, p < 0.001) and a lower percentage of global LV hypokinesia (4.8% vs. 94.2%, p < 0.001). The mean survival time was higher among patients with LVEF ≥ 50% than those with LVEF = 41-49% and ≤ 40% (p = 0.014 and 0.001, respectively). The hazard of death was 4.42 and 5.40 times greater in patients with LVEF ≤ 40% or with global LV hypokinesia, respectively. Regression revealed that the global LV hypokinesia, ECG abnormalities, and decreased LVEF and oxygen saturation were significantly associated with the risk of death (hazard ratios: 4.382, 3.348, 0.957, and 0.971, respectively). Conclusions: Echocardiography represents a valuable diagnostic tool to assess cardiac function in acute AlP poisoning. Both LVEF and global LV hypokinesia significantly impact the survival of AlP-poisoned patients. Echocardiography was superior to ECG changes in terms of accuracy for the prediction of mortality.
... In addition, garlic or rotten fish may be inhaled from the patient's breathing in both types of poisoning (Moghadamnia and Abdollahi, 2002;Sinha, 2018;Navabi et al., 2018). So far, Melatonin (Asghari et al., 2017;Hsu et al., 2000;Hsu et al., 2002), Magnesium (Siwach et al., 1994;Siwach et al., 1995), Levocimendan (Gupta et al., 2015), coconut oil (Bajwa et al., 2010;Shadnia et al., 2005;Agrawal et al., 2015), Sodium Selenite, N-Acetyl Cysteine (Taghaddosinejad et al., 2016;Manouchehri et al., 2019), Acetyl-L-Carnitine (Baghaei et al., 2016), Vitamin E (Halvaei et al., 2017), Triiodothyronine (Abdolghaffari et al., 2015), Liothyronine (Goharbari et al., 2018), Vasopressin and Millerinone , Laurus nobilis L. leaf extract (Türkez and Toğar, 2013), Glucose-6-phosphate Dehydrogenase PD enzyme (G6PD) (Salimi et al., 2017) and Boric acid (Soltani et al., 2013;Sweilum et al., 2017) has been reported for the treatment of aluminum phosphide poisoning, but these studies are limited and do not have the necessary comprehensiveness, so virtually no antidote to this poisoning has been introduced so far. ...
... There is no specific antidote that reverses the effects of aluminum phosphide. Antioxidants like N-acetylcysteine, sodium selenite, vitamin E, liothyronine, calcitriol and melatonin have been tried as antidotes to aluminum phosphide but with very limited success [95][96][97][98][99][100]. Intravenous lipid emulsion (ILE) has been reported to reverse the toxic systemic effect of acute aluminum phosphide self-ingestion. ...
Article
Full-text available
Due to its easy availability, rapid and severe toxicity, and no specific antidote, aluminum phosphide has emerged as a lethal toxin, commonly used for suicidal intent in agricultural communities. Despite various advances in medicine, this compound’s toxicity is poorly understood, and it still has a very high case fatality rate with no definitive treatment options available. This review aims to understand the mechanism of toxicity, clinical toxidrome of acute aluminum phosphide poisoning, and the available therapeutic options, including recent advances. A literature review was performed searching PubMed, EMBASE Ovid, and Cochrane Library, using the following search items: (“aluminum phosphide poisoning” OR “aluminum phosphide poisoning toxicity” OR “aluminum phosphide ingestion”) AND (“management” OR “therapy” OR “treatment”). Selected articles were discussed amongst all the authors to shape this review. High case fatality rate and lack of any specific antidote are persisting challenges. Therapeutic measures need to be implemented from all fronts – reducing easy access to the poison, developing less toxic alternatives for use as a pesticide, and more studies directed at developing an effective reversal agent for phosphine. The advent of promising agents like glucose-insulin-potassium infusion and lipid emulsion is a new ray of hope in the complete recovery in this fatal poisoning. The current need of the hour is to find an agent that rapidly and effectively reverses aluminum phosphide's toxic effects. Large multicenter controlled trials are required to establish the role of glucose-insulin-potassium and lipid emulsion.
... Vitamin E has shown to prevent destruction of hepatocytes secondary to phosphine-induced lipid peroxidation. [80] Renal Support ...
Article
Full-text available
Agricultural revolution and increasing pesticidal use have brought its share of downsides in the form of pesticidal poisoning. Every year approximately 300,000 deaths happen worldwide due to pesticide poisoning. Organophosphates, chlorates, and aluminum phosphide are the commonly used pesticides. Alkaline phosphatase (ALP) is the most lethal among the available pesticides and no antidote is available and aptly called as suicide poison. The common use and easy availability of ALP is causing acute and chronic health effects which have reached major proportions in Asian and Middle Eastern countries such as India, Bangladesh, Iran, Jordan, and Sri Lanka. Toxicity of ALP is related to prompt release of lethal phosphine gas as ALP tablet absorbs moisture. Phosphine gas mainly affects cardiovascular system gastrointestinal tracts, lungs, and kidneys. The clinical features of poisoning include nausea, vomiting, abdominal pain, pulmonary edema, cyanosis shock arrhythmias, and alter sensorium. Diagnosis of ALP poisoning largely depends on history and clinical setting and treatment is usually initiated without waiting for silver nitrate paper test or gastric aspirate analysis. Treatment includes early gastric lavage symptomatic supportive therapy and palliative care. There has been greater understanding about the mechanism and pathophysiology of ALP toxicity over the years, although that cannot be commented about the treatment modalities. Government efforts to restrict sale have been offset by the lack of strict enforcement by regulatory agencies. Case fatality rates from ALP poisoning have shown some decline over the years due to early supportive management. Different treatment modalities and protocols have been tried at various centers with variable success; however, further research for an antidote is the need of the hour. Key words: Aluminum Phosphide; Phosphine; Phosphide; Pesticides; Poisoning; Silver Nitrate Test; N-acetylcysteine; Magnesium Sulfate
... Aluminum phosphide (AlP), also known as rice tablet, is used as a fumigant to protect stored grains against insects and rodents [1]. The toxic effects of AlP are promoted through the toxic phosphine gas (PH3), which is produced via contact with water, air humidity or gastric acid [2,3]. ...
Article
Full-text available
Abstract Background & Objective: Aluminum phosphide (AlP) is a pesticide that is commonly used, which could cause poisoning mainly through the induction of oxidative stress. The present study aimed to evaluate the effects of nano-curcumin and curcumin on the oxidant and antioxidant system in the liver mitochondria in AIP-induced experimental toxicity. Materials and Methods: In this study, 36 male albino Wistar rats were randomly divided into six groups (n=6). The control subjects and animals poisoned with AlP (2 mg/kg) received treatment with and without nano-curcumin (100 mg/kg) and curcumin (100 mg/kg) for seven days. Mitochondria were isolated from the liver and analyzed in terms of lipid peroxidation (LPO), total antioxidant capacity (TAC), total thiol groups (TTGs), superoxide dismutase (SOD), and catalase activity. In addition, mitochondrial viability was assessed. Results: AlP caused a significant increase in the LPO levels, while significantly decreasing TAC, TTG, SOD, catalase activity, and mitochondrial viability compared to the controls (P<0.05). Moreover, nano-curcumin treatment significantly enhanced TAC, TTG, SOD, and mitochondrial viability (P<0.05). Curcumin could also improve TTG and mitochondrial viability (P<0.05). Conclusion: According to the results, nano-curcumin exerted protective effects against AlP-induced experimental toxicity, and the effect was attributed to the antioxidant properties of this compound. Keywords: Nano-curcumin, Curcumin, Aluminum Phosphide, Mitochondria, Oxidative Stress
... In addition, Halvaei et al. [22] investigated the therapeutic effect of vitamin E in acute aluminum phosphide poisoning and proved its efficacy as a novel treatment for this type of poisoning. Furthermore, Nagda et al. [23] showed the preventive role of vitamin E wherein the supplementation of diet with vitamin E for the exposed workers to endosulfan can minimize its toxicity. ...
Article
Full-text available
It is known that vitamins play a key role in many physiological processes in the human body such as metabolism and immunity. Several of the recent studies revealed that a number of vitamins may use as an alternative or adjuvant therapy or preventive agent in the numerous cases of drugs and chemicals intoxication. Vitamins C, E, and A were known to possess antioxidant properties and various studies indicated that these vitamins have the ability to scavenge the reactive oxygen species generated in the body due to toxicant exposure. In addition, few of the findings proved the potential and clinical utility of vitamins B and D in treating the cases of toxicity.
Article
Full-text available
Aluminum phosphide (ALP) (celphos) is an agricultural pesticide commonly implicated in poisoning. Literature pertaining to the clinical manifestations and treatment outcome of its poisoning among children is limited. A retrospective chart review was conducted of the medical records of 30 children aged less than 14 years admitted to pediatric intensive care unit (PICU) of a tertiary care hospital in northern India. Demographic, clinical, and laboratory parameters were recorded. The outcome was categorized into "survivors" and "nonsurvivors." The Mean (SD) age of the enrolled children [19 males (63.3%)] was 8.55 (3.07) years. Among the 30 children, 14 (46.67%) were nonsurvivors and the rest 16 (53.33%) were survivors. Nonsurvivors had ingested significantly higher doses of ALP (P < 0.001), and showed higher time lag to PICU transfer (P 0.031), presence of abnormal radiological findings on chest skiagram (P = 0.007), and a higher Pediatric Risk of Mortality (PRISM) III score (P < 0.001) at admission. Use of magnesium sulfate was associated significantly with survival [odds ratio (OR) (95% CI): 0.11 (0.02-0.66); P 0.016]. The present study highlights that survival among children with ALP poisoning is predicted by dose of ALP ingestion, time lag to medical attention, and higher PRISM score at admission. Use of magnesium sulfate could be associated with better survival among them.
Article
Full-text available
Aluminum phosphide (ALP), a widely used fumigant and rodenticide, leads to high mortality if ingested. Its toxicity is due to phosphine that is liberated when it comes in contact with moisture. The exact site or mechanism of action of phosphine is not known, although it is widely believed that it affects mitochondrial oxidative phosphorylation. Basic serum biochemical parameters, activity of mitochondrial complexes, antioxidant enzymes and parameters of oxidative stress were estimated in the platelets of 21 patients who developed severe poisoning following ALP ingestion. These parameters were compared with 32 healthy controls and with 22 patients with shock due to other causes (cardiogenic shock (11), septic shock (9) and hemorrhagic shock (2)). The serum levels of creatine kinase-muscle brain and lactate dehydrogenase were higher in patients poisoned with ALP, whereas a significant decrease was observed in the activities of mitochondrial complexes I, II and IV. The activity of catalase was lower but the activities of superoxide dismutase and glutathione peroxidase were unaffected in them. A significant increase in lipid peroxidation and protein carbonylation was observed, whereas total blood thiol levels were lower. In patients severely poisoned with ALP, not only cytochrome c oxidase but also other complexes are involved in mitochondrial electron transport, and enzymes are also inhibited.
Article
Full-text available
Background: Aluminum phosphide (AlP) is also known as "rice tablet" in Iran. Due to the high incidence of acute AlP poisoning and its associated mortality in Iran, the authorities banned AlP-containing tablets in 2007. The aim of this study is to evaluate the trend of acute fatal AlP poisoning subsequent to this restriction. Materials and methods: 0 This is a retrospective chart review of patients with acute "rice tablet" poisoning who were admitted to Loghman Hakim Hospital Poison Center, Tehran, Iran, from 2007 to 2010. Collected information included gender, age, type of poisoning, marital status, duration of hospitalization, and outcome. Results: There were 956 cases with a mortality rate of 24.06%. The incidence of fatal AlP poisoning was 2.1 and 5.81 per one million populations of Tehran in 2007 and 2010, respectively. In 223 of the fatal cases (97%) and 697 of the non-fatal cases (96%), the poisoning was intentional. The male to female ratio in the fatal and non-fatal cases was 1.04:1 and 1:1.3, respectively. Most of the fatal cases (n = 122, 53%) were unmarried. The mean age was 27.32 ± 11.31 and 24.5 ± 8.19 years in fatal and non-fatal cases, respectively. In 196 (85.2%) of the fatal cases and in 577 (79%) of non-fatal cases, the duration of hospitalization was less than 24 hours and between 48-72 hours, respectively. Conclusion: The results of this study showed the incidence of "rice tablet" poisoning, and its mortality increased since 2007 in spite of the ban. It seems that legislative means alone without other interventions, such as suicide prevention and public education, will not always be able to control or prevent acute intentional poisonings.
Article
Full-text available
Aluminum phosphide (AlP) is a cheap solid fumigant and a highly toxic pesticide which is commonly used for grain preservation. In Iran it is known as the "rice tablet". AlP has currently aroused interest with increasing number of cases in the past four decades due to increased use in agricultural and non-agricultural purposesand also its easy availability in the markets has increased its misuse to commit suicide. Upon contact with moisture in the environment, AlP undergoes a chemical reaction yielding phosphine gas, which is the active pesticidal component. Phosphine inhibits cellular oxygen utilization and can induce lipid peroxidation. It was reported that AlP has a mortality rate more than 50% of intoxication cases. Poisoning with AlP has usually occurred in attempts to suicide. It is a more common case in adults rather than teen agers. In some eastern countries it is a very common agent with rapid action for suicide. Up to date, there is no effective antidote or treatment for its intoxication. Also, some experimental results suggest that magnesium sulfate, N-acetyl cysteine (NAC), glutathione, vitamin C and E, beta-carotenes, coconut oil and melatonin may play an important role in reducing the oxidative outcomes of phosphine. This article reviews the experimental and clinical features of AlP intoxication and tries to suggest a way to encounter its poisoning.
Article
Full-text available
Objective: Aluminum phosphide is used as a fumigant. It produces phosphine gas (PH₃). PH₃ is a mitochondrial poison which inhibits cytochrome c oxidase, it leads to generation of reactive oxygen species; so one of the most important suggested mechanisms for its toxicity is induction of oxidative stress. In this regard, it could be proposed that a drug like N-acetylcysteine (NAC) as an antioxidant would improve the tolerance of aluminum phosphide-intoxicated cases. The objective of this study was to evaluate the protective effects of NAC on acute aluminum phosphide poisoning. Methods: This was a prospective, randomized, controlled open-label trial. All patients received the same supportive treatments. NAC treatment group also received NAC. The blood thiobarbituric acid reactive substances as a marker of lipid peroxidation and total antioxidant capacity of plasma were analyzed. Results: Mean ingested dose of aluminum phosphide in NAC treatment and control groups was 4.8 ± 0.9 g vs. 5.4 ± 3.3 g, respectively (p = 0.41). Significant increase in plasma malonyldialdehyde level in control group was observed (139 ± 28.2 vs. 149.6 ± 35.2 μmol/L, p = 0.02). NAC infusion in NAC treatment group significantly decreased malondialdehyde level (195.7 ± 67.4 vs. 174.6 ± 48.9 μmol/L, p = 0.03), duration of hospitalization (2.7 ± 1.8 days vs. 8.5 ± 8.2 days, p = 0.02), rate of intubation and ventilation (45.4% vs. 73.3%, p = 0.04). Mortality rate in NAC treatment and control groups were 36% and 60%, respectively with odds ratio 2.6 (0.7-10.1, 95% CI). Conclusion: NAC may have a therapeutic effect in acute aluminum phosphide poisoning.
Article
Full-text available
According to previous animal studies, aluminium phosphides (AlPs) may induce oxidative stress leading to generation of free radicals and alteration in antioxidant defense system. This study was conducted to evaluate the existence and degree of oxidative stress in patients with acute AlP ingestion. A total of 44 acute AlP ingested patients as well as 44 age- and sex-matched controls were included. All patients had acute poisoning symptoms with AlP at the time of presentation and had blood samples analyzed for lipid peroxidation, total antioxidant capacity and total thiol. Our findings showed that there is a significant increase in lipid peroxidation in AlP ingested group along with a reduction in total antioxidant capacity and total thiols groups. These clinical data confirm previous experimental models that showed AlP exposure might significantly augment lipoperoxidative damage with simultaneous alterations in the antioxidant defense system. Hence, our findings might justify use of antioxidants in treatment of acute AlP poisoning which needs to be clarified by additional clinical trials.
Article
Aluminum phosphide (AlP), a widely used fumigant and rodenticide leads to high mortality if ingested. Its toxicity is due to phosphine liberated when it comes in contact with moisture. The exact mechanism of action of phosphine is not known. In this study male Wistar rats were used. The animals received a single dose (20mg AlP/kg body weight i.g.) orally. Basic serum biochemical parameters, activity of mitochondrial complexes, antioxidant enzymes and parameters of oxidative stress, individual mitochondrial cytochrome levels were measured along with tissue histopathology and immunostaining for cytochrome c and compared with controls. The serum levels of creatinine kinase-MB, lactate dehydrogenase, magnesium and cortisol were higher (p<0.01); the activities of mitochondrial complexes I, II, IV were observed to be significantly decreased in liver tissue in treated rats (p<0.01). The activity of catalase was lower (p<0.05) with a significant increase in lipid peroxidation (p<0.05) whereas superoxide dismutase and glutathione peroxidase were unaffected in them. There was a significant decrease in all the cytochromes in brain and liver tissues (p<0.05) with the exception of cytochrome b in brain, the levels of which remained same. Histopathology revealed congestion in most organs with centrizonal hemorrhagic necrosis in liver. Ultra structural changes indicating mitochondrial injury was observed in heart, liver and kidney tissues. There was also a marked reduction in the cytochrome-c immunostaining compared to the controls. Toxicity due to AlP appears to result as a consequence of both-energy insufficiency and oxidative stress, with a possible and preferential interaction with the tissue cytochromes.
Article
Metal phosphides in general and aluminium phosphide in particular are potent insecticides and rodenticides. These are commercially used for protection of crops during storage, as well as during transportation. However, these are highly toxic substances. Their detrimental effects may range from nausea and headache to renal failure and death. It is, therefore, pertinent to ensure their circumspect handling to avoid poisoning episodes. Its poisoning has a high mortality and recent years have seen an increase in the number of poisoning cases and deaths caused by suicidal ingestion. Yet due to their broad spectrum applications, these chemicals cannot be written off. The present communication reviews the various aspects of toxicity associated with metal phosphides.
Article
Aluminum phosphide (ALP), a widely used insecticide and rodenticide, is also infamous for the mortality and morbidity it causes in ALP-poisoned individuals. The toxicity of metal phosphides is due to phosphine liberated when ingested phosphides come into contact with gut fluids. ALP poisoning is lethal, having a mortality rate in excess of 70%. Circulatory failure and severe hypotension are common features of ALP poisoning and frequent cause of death. Severe poisoning also has the potential to induce multi-organ failure. The exact site or mechanism of its action has not been proved in humans. Rather than targeting a single organ to cause gross damage, ALP seems to work at the cellular level, resulting in widespread damage leading to multiorgan dysfunction (MOD) and death. There has been proof in vitro that phosphine inhibits cytochrome c oxidase. However, it is unlikely that this interaction is the primary cause of its toxicity. Mitochondria could be the possible site of maximum damage in ALP poisoning, resulting in low ATP production followed by metabolic shutdown and MOD; also, owing to impairment in electron flow, there could be free radical generation and damage, again producing MOD. Evidence of reactive oxygen species-induced toxicity owing to ALP has been observed in insects and rats. A similar mechanism could also play a role in humans and contribute to the missing link in the pathogenesis of ALP toxicity. There is no specific antidote for ALP poisoning and supportive measures are all that are currently available. Copyright © 2011 John Wiley & Sons, Ltd.