IN VIVO AND EX VIVO STUDIES ON AMELIORATIVE EFFECT OF QUERCETIN ON STRUCTURAL AND FUNCTIONAL CHANGES INDUCED BY CADMIUM IN UTERUS OF MICE
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Date
2019-01
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SRI VENKATESWARA VETERINARY UNIVERSITY TIRUPATI - 517502. (A.P.) INDIA
Abstract
Uterine abnormalities either hereditary or acquired are the major cause of
infertility among reproductive females that leads to recurrent miscarriages,
spontaneous abortions, pre-term labour, infertility etc. Cadmium is an important
endocrine disruptor and reproductive toxicant causing uterine abnormalities.
Quercetin, a powerful antioxidant flavonoid has the ability to scavenge the free
radicals and also has heavy metal chelating property, smooth muscle relaxant
property and estrogenic effect. The present study evaluated the structural and
functional changes caused by cadmium in mice myometrium and also evaluated the
ameliorative effect of quercetin on cadmium induced myometrial changes.
The study was conducted in four groups. Group I considered as control with
apparently healthy animals, group II consisted of animals that received cadmium @
30ppm in drinking water for 30 days. The group III animals were treated with
cadmium @30 ppm in drinking water and simultaneously with quercetin at 50 mg/kg
bw orally for 30 days and group IV consisted of animals that received quercetin alone
@ 50mg/Kg bw orally. Among each group, estrus was induced in half of the animals
with estradiol benzoate whereas other animals were sacrificed when they were on
non-estrus stage. After sacrifice uterine horn was isolated to use for functional studies
using digital polygraph. The liver and kidney homogenate were used for estimation
of tissue antioxidant markers like GSH and SOD and peroxidation marker like
TBARS. The mice uterus, liver and kidney were collected for histopathological
changes. The increased TBARS level and decreased SOD and GSH levels were
observed in both liver and kidney of cadmium treated group compared to control
indicating peroxidative damage by cadmium to various tissues of mice and it was
reversed back in cadmium along with quercetin treated group compared to cadmium
group that showed an antioxidant protective effect of quercetin on cadmium damage.
The alerations in histological structure of liver, kidney and uterus in cadmium treated
groups were rectified to normal architecture in cadmium along with quercetin treated
animals. The mean EC 50 values of oxytocin contractile dose amplitude and frequency
response in cadmium treated estrus mice were 9.344x10-13 and 8.864x10-13
respectively and it was significantly lower than control estrus mice. The simultaneous
administration of cadmium along with quercetin to estrus mice increases the mean
EC50 value of oxytocin induced amplitude of contraction from 9.344x10-13 to
1.306x10-12, but it was not comparable to control indicating protective effect of
quercetin. The mean EC50 of oxytocin dose amplitude contractile response in
cadmium along with quercetin treated non-estrus mice was lower than control and
cadmium. The mean EC50 value of KCl induced amplitude and frequency of
contractile response in cadmium along with quercetin treated estrus mice showed a
higher value (8.81x10-4 and 8.401x10-4) compared to cadmium group (5.686x10-4
and 5.778x10-4) and also the KCl induced amplitude of contraction showed a
significantly higher EC50 value than control group. Hence we can conclude that
cadmium produces significant estrogen mimicking effect in estrus myometrium and
quercetin was found to have non-uniform effects due to its contradictory actions on
myometrium.
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