PATHOMORPHOLOGICAL STUDIES ON LEAD TOXICITY IN FEMALE RATS WITH SPECIAL REFERENCE TO THE REPRODUCTIVE SYSTEM AND ITS AMELIORATION WITH Emblica officinalis (AMLA) AND Linum usitatissimum (FLAXSEED)
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Date
2017-10
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SRI VENKATESWARA VETERINARY UNIVERSITY TIRUPATI - 517 502. (A.P.) INDIA
Abstract
ABSTRACT:
Heavy metal Lead is one of mankind’s oldest environmental and
occupational toxins found in almost all phases of biological systems. It is known to
cause many adverse effects in man and animals. The major organs affected in the
body in lead toxicity include nervous system, renal system, hematologic,
cardiovascular and immune system. The deleterious effects of lead on reproductive
system both in males and females are also a well-known fact. Animal models are
widely used to characterize lead toxicity and to study the ameliorating effects of
many herbs. In the current investigation, Emblica officinalis (AMLA) and Linum
usitatissimum (FLAXSEED) are being investigated for their protective effect on
lead induced toxicity with a major focus on reproductive system of female wistar
rats. The present study was carried out by procuring 108 female adult wistar
albino rats that were randomly assigned to 6 groups with 18 rats in each group.
Group I served as vehicle control and they received distilled water, whereas
animals in Group II, III, IV, V and VI received lead acetate @ 60 mg/ kg b.wt.,
Emblica officinalis @ 100 mg/ rat/ day, Linum usitatissimum @ 300 mg/ kg b.wt,
lead acetate @ 60 mg/ kg b.wt + Emblica officinalis @ 100 mg/ rat/ day, lead
acetate @ 60 mg/ kg b.wt + Linum usitatissimum @ 300 mg/ kg b.wt. respectively
for 45 days. Six rats from each group were sacrificed at fortnight intervals.
In the present study no mortality was observed in any of the treated group.
Across the groups, lead related clinical signs attributable to neurotoxicity were
seen. Significant (P<0.05) reduction was recorded in TEC, PCV, Hb and Percent
lymphocyte count and significant increase in Percent neutrophil count and TLC
was observed in lead treated group (II) in relation to group I. These counts were
significantly improved in ameliorated groups (V and VI), when compared to lead
treated group (II). Serum biochemical analysis revealed significant decrease (P<0.05) in total
protein and increase in SGPT, SGOT, cholesterol, creatinine, ALP and LDH levels
in Group II. Significant (P<0.05) increase in the concentration of TBARS and
decreased levels of antioxidants like catalase, SOD and GPx levels in liver, kidney,
brain and uterus of Group II were noticed. The levels of these parameters were
significantly improved in the ameliorated group (Group V and VI).
Significant (P<0.05) decrease in serum Progesterone (P) and Estrogen (E2)
concentration was noticed in Group II rats. In Group V and VI, significant
improvement in hormonal values was noticed compared to Group II. No
significant alterations were noticed in all above mentioned parameters in Emblica
and Flaxseed treated rats (Group III and IV). In the present study, conspicuous gross lesion was noticed in uterus, liver followed by kidney and lung. Gross lesion includes reduction in size of uterus, paleness of liver, congestion of kidney and lung in lead treated rats (Group II).
These changes were less severe in Group V and VI. No significant changes were
observed in Emblica and Flaxseed treated rats (Group III and IV).
Microscopically uterus of the rats of Group II revealed vacuolar
degeneration of lining epithelium of endometrium, narrowing of lumen,
degenerated endometrial glandular epithelium, disruption of endometrial glandular
structure with, reduced number of endometrial glands, variation in shape and size
of the glands, severely degenerated and distorted glands, cystic lumen, complete
obliteration of glandular lumen and hyperplastic changes in endometrial gland. In
Group V and VI, these changes were less intense.
Ovaries of lead acetate treated rats showed, medullary congestion,
thickened tunica albuginea, severely degenerated granulosa cell with completely
disintegrated oocyte and its nucleus in primary and secondary follicles, lysis of
oocyte, cumulus oophorus and clumping of granulosa cells in secondary follicle
and significant reduction in the number of follicles at different developmental
stages were observed. All these changes were less severe in groups (V and VI).
Microscopically, the panel of vital organs comprising liver, kidney, heart,
spleen, intestine and lungs were evaluated. The major changes in liver included
focal loss of hepatocytes with infiltration of MNCs, bile duct hyperplasia,
moderate to severe dilatation and congestion of sinusoids in group II animals.
Kidney section showed degenerated and desquamated renal tubular epithelium,
congested glumerulus, atrophied and cystic glomeruli. The lead acetate treated
group also showed mild to severe thickening of interstitial space, thickening of
blood vessels, and severe lymphoid hyperplasia in peribronchial area in lungs. The
lesions in brain section included submeningeal hemorrhages, mild to moderate
capillary proliferation in cerebral cortex, rounding and loss of purkinje cells in
cerebellum, shrinkage of neurons, demyelinating changes and spongiosis and
gliosis. Heart showed focal sarcolytic changes, thickening and congested blood
vessels. Changes in spleen included thickened blood vessels, thickened capsule
and mild to moderate depletion of lymphocyte in white pulp and engorgement of
red pulp. Intestine revealed desquamated epithelial cells with increased number of
goblet cells, mild to moderate eosinophilic infiltration in sub mucosa and necrosis.
The severity of these lesions was of lesser magnitude in Group V and VI. No
significant changes were noticed in soft tissues of Emblica (Group III) and
Flaxseed (Group IV) treated rats. In rats of group II, immunohistochemistry showed increased expression of BAX marker in both uterus and ovarian tissue compared to Group I. Whereas, in rats of Group V and VI decreased expression of BAX marker was observed
compared to Group II. No significant changes were noticed in rats of Group III and
IV.
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