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Nutrient Mixture Attenuates Acetaminophen Hepatic and Renal Toxicity
in ICR Mice
M.W. Roomi, V. Ivanov, A. Niedzwiecki, M. Rath
Dr. Rath Research Institute, 1260 Memorex Drive, Santa Clara,
CA 95050
Presented at: Society of Toxicology, San Diego,
CA, March 5-9, 2006
Published in: The Toxicologists (suppl Toxicological
Sciences) 90 (1), Abstract 1398, pg 285, 2006.
Abstract
Introduction:
Drugs based on acetaminophen, such as Tylenol, are available without
prescription and commonly used to fight fever and pain. A large
overdose
of acetaminophen (APAP) is often fatal, leading to fulminant hepatic
and
renal tubular necrosis in humans and animals. A unique nutrient
formulation consisting of lysine, proline, ascorbic acid and green
tea
extract (NM) has previously been demonstrated to exhibit a broad
spectrum of pharmacological, therapeutic, cardio vascular and
chemoprotective properties.
Objective:
This study was undertaken to determine whether NM is useful in
treatment of APAP-induced hepatic and renal damage.
Materials and Methods:
Six-week-old male ICR mice were divided into four groups (A-D)
of five animals each: Group A (control) received corn oil, group
B received APAP (600 mg/kg, ip), group C was fed NM (0.5%) for
two weeks, and group D was dosed with APAP after feeding with
NM (0.5%) for two weeks. All animals were sacrificed after 24
hrs, serum was collected for liver and kidney functions, and liver
and kidney were excised for histology.
Results:
APAP treatment (groups B and D) resulted in a marked increase
in liver and kidney weights. Serum AST and ALT in groups A and
C were comparable, increased markedly in group B and significantly
reduced in group D. APAP caused significant centrilobular necrosis
in group B animals, while NM prevented these alterations in group
D. Serum markers of kidney: BUN, creatinine and BUN/creatinine
ratio were markedly increased in group B in contrast to groups
A and C. The NM fed group D exhibited biochemical parameters similar
to control group A. The kidney of APAP intoxicated mice (B) showed
severe acute damage to the glomerulus and proximal tubule in contrast
to the kidneys of mice fed with NM (D), which demonstrated a nearly
normal histological pattern.
Conclusions:
The results indicate that NM has potential to protect against
APAP-induced liver and kidney damage.
Comment:
Overdosing with acetaminophen, a common over-the-counter analgesic,
is often fatal, causing severe liver and kidney damage in
humans and animals. We tested the protective effect of a nutrient
supplemented diet (0.5% NM) in mice injected ip with acetaminophen
(600 mg/kg) using a nutrient mixture that has previously demonstrated
therapeutic and chemoprotective properties. The nutrient supplemented
mice were protected against acetaminophen-induced liver and
kidney damage, while the unsupplemented mice exhibited liver
and kidney pathology and associated serum enzyme abnormality.
Thus, the nutrient mixture provides protection against acetaminophen-induced
hepatic and renal damage. |
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