Effects Of Lead Administration Research Articles

Pathomorphological Changes during Amelioration of Lead Induced Toxicity in Chickens by Withania somnifera

One hundred and fifty, day-old broiler chicks were divided into five groups of 30 birds each. Group I was kept as control. Groups II and III were administered 250 and 400 ppm lead acetate in distilled water, respectively. Groups IV and V were administered 250 and 400 ppm of lead in distilled water along with Withania somnifera root powder (WSRP) in standard recommended feed at 1% concentration from 2 weeks of age till 60 days post-treatment (DPT). Pathological studies were done by sacrificing three birds from each group at 7, 14, 21, 28, 35, 42, 49 and 60 DPT. No gross as well as histopathological, lesion could be recorded in Group I. Grossly, in Groups II and III, congestion was seen in liver, kidneys and lungs, whereas ecchymotic haemorrhage along with congestion were evident in intestine. Spleen and testes decreased in size with mild congestion. Pinpoint haemorrhagic lesions were observed in the thymus. There was slight decrease in the size of bursa of Fabricius. No significant gross lesions were observed in Groups IV and V. Histopathologically, liver, kidney, intestine, lungs, heart, brain and testes, initially, showed vascular lesions like congestion and haemorrhage along with degenerative changes while later on these organs evinced necrotic and inflammatory lesions comprising of mononuclear cell infiltration. Spleen, bursa of Fabricius and thymus revealed vascular lesions along with mild depletion of lymphoid cells initially and severe lymphoid depletion in later stages. Ultrastructurally, liver, kidney and intestine showed distorted nucleus with margination of chromatin material, swollen mitochondria with regressed cristae and increased number of lysosomes. Lesions were less severe in Groups IV and V than Groups II and III. It was concluded from this study that 1% WSRP administration significantly ameliorate the effect of lead administration at 250 and 400 ppm on tissue changes in chickens.

Effects of lead administration at low doses by different routes on rat spleens. Study of response of splenic lymphocytes and tissue lysozyme.

The aim of this study was to evaluate the effects of low doses of lead (200 ppm of PbAc(2) for 4 weeks) on rat spleens using different routes of administration. The study has been carried out at different levels: a histological evaluation has been made, and alterations of cell proliferation, B and T lymphocyte subpopulations, and CD4(+) and CD8(+) T cell subpopulations have been evaluated. Apoptosis and necrosis of lymphoid cells were also analysed. Furthermore, lysozyme activity was measured. Results indicate a large increase in spleen size when lead is administered by intraperitoneal injection, being this route in which lead causes larger modifications in all of the parameters measured. Lead administered orally causes histological modifications, such as an increase in the number of lymphocytes as well as edema. However, significant alterations in other parameters studied have not been detected. Lead administration by intraperitoneal route causes more evident histological modifications as well as an increase in the number of lymphocytes, and also induces a decrease in the percentage of B(+), T(+) and CD4(+) cells, and an increase in CD8(+) cells. Cell death of splenic lymphocytes is not altered by lead. With regard to the immune innate response, lead behaves as an immunomodulator as can be deduced from data on lysozyme activity in tissue. Therefore, it is possible to affirm that the effect of low doses of lead depends on the route of administration. Thus, the intraperitoneal route, through which lead goes directly to the bloodstream, causes drastic effects, generating important immunological alterations.

Histological and Histochemical Alterations in the Kidney Induced by Lead

Although lead intoxication is one of the most common forms of metal intoxication, the histochemical alterations in the renal tissues due to chronic lead exposure is limited and has not yet been well identified. A total of 60 male Wistar albino rats (Rattus norvegicus) were exposed to lead acetate trihydrate (0.0, 0.25, 0.5, 1.0 and 2% for 1 to 12 months) in drinking water to investigate the histological and histochemical alterations in the renal tissues due to lead. Chronic exposure to subtoxic doses of lead produced distinct progressive tubular, glomerular and interstitial damages. Tubular changes occurred earlier than glomerular and interstitial ones, and included anisokaryosis, nuclear pyknosis, karyomeglay, development of intranuclear and cytoplasmic inclusions together with tubular dilation, necrosis, vacuolization, tubular hyperplasia and solid tubular adenoma. The glomerular alterations were mainly mesangial hypercellularity, segmental proliferation, focal and segmental glomeruloscleriosis, glomerural hyalinization and glomerular tuft alterations. The findings indicate that lead produces significant histological and histochemical changes in the kidney that lead to severe complications.

Central lead administration inhibits water intake and sodium appetite in rats.

We have demonstrated that acute third ventricle injections of lead acetate (PbAc) exert a powerful antidipsogenic effect and induce a significant increase in renal sodium excretion. In the present study we confirm the antidipsogenic effect of lead and demonstrate that central administration of this metal, in minute amounts, significantly reduces salt intake both during dehydration and after central angiotensinergic stimulation. Adult male Wistar rats had the third ventricle cannulated seven days before the experiments. During this period they had free access to distilled water and hypertonic saline solution (1.5%). After a 24-h period of fluid deprivation, experimental animals received third ventricle injections of PbAc (0.3, N = 8 and 3.0 nmol/rat, N = 14) while controls received sodium acetate (NaAc; 3.0 nmol/rat, N = 10). Rats treated with PbAc at the highest dose showed a significant reduction (P<0.05) both in water and hypertonic saline intake when compared to controls. When the effect of lead administration on angiotensin II-induced water and salt intake was studied, normohydrated animals received third ventricle injections of angiotensin II (9.6 nmol/rat) after pretreatment with 3.0 nmol/rat of PbAc (experimental group, N = 10) or NaAc (controls, N = 8). The group pretreated with PbAc presented a significant reduction (P<0.05) in both water and salt intake compared to controls. Thus, this study confirms the antidipsogenic effect of central lead injections and demonstrates that the presence of lead in the brain exerts a significant inhibition of sodium appetite.

AcuteLead Acetate Administration Potentiates Ethanol‐Induced Locomotor Activity in Mice: The Role of Brain Catalase

It has been proposed that brain catalase plays a role in the modulation of some psychopharmacological effects of ethanol. The acute administration of lead acetate has demonstrated a transient increase in several antioxidant cell mechanisms, including catalase. In the present study, we investigated the effects of acute lead acetate administration on ethanol-induced behavior, brain catalase activity, and the relation between both effects. Lead acetate (100 mg/kg) or saline was injected intraperitoncally in mice. At different intervals of time (1, 3, 5, 7, 9, or 11 days) after this treatment, ethanol (2.5 g/kg) was injected intraperitoneally and the mice were placed in open field chambers. Results indicated that the locomotor activity induced by ethanol was significantly increased. Maximum ethanol-induced locomotion increase (70% more activity than control animals) was found in animals treated with lead acetate 7 days before ethanol administration. Total brain catalase activity in lead-pretreated animals also showed a significant induction, which was maximum 7 days after lead administration. A significant correlation was found between both effects of locomotor and catalase activity. In a second study, the effect of lead administration on d-amphetamine (2.0 mg/kg) and tert-butanol-(0.5 g/kg) induced locomotor activity was investigated. Lead acetate treatment did not affect the locomotion induced by these drugs. These data suggest that brain catalase is involved in ethanol's effects. They also provide further support for the notion that acetaldehyde may be produced directly in the brain via catalase and that it may be a factor mediating some of ethanol's central effects.

Effects of Lead Administration on Developing Rat Kidney

The effects of chronic lead administration on renal function and cytoarchitecture and on the immunohistochemical localization of glutathione S-transferase (GST) isoenzymes were determined. Pregnant rats were given 250 ppm lead acetate in drinking water from conception until weaning and mothers and pups received 500 ppm of lead acetate from weaning until termination at either 3 or 7 weeks of age. Light and electron microscopic studies after 3 weeks of lead administration showed tubular injury with frequent mitoses noted in proximal tubular cells and, after 7 weeks of treatment, interstitial fibrosis, characteristic intranuclear inclusions, and tubular injury characterized by both nuclear and cytoplasmic pleomorphism. Rats treated with lead for 7 weeks showed significantly lower body weights and creatinine clearances than age-matched control animals. Immunohistochemical studies of glutathione transferase subunits in control rats showed unique isoform localization in each segment of the nephron; treatment with lead caused large increases in immunoreactive protein of Yc, Yk, Yb1, and Yp GST subunits in proximal tubules. No increases in the antioxidant enzymes copper-zinc superoxide dismutase, catalase, and glutathione peroxidase were found in lead-treated rats, but there was a diffuse lead-related increase in immunoreactive protein for manganese superoxide dismutase throughout the renal cortex. Our results demonstrate large lead-induced increases of specific isoforms of glutathione S-transferase in specific kidney cell types and show that these increases preceded irreversible renal damage.

Effects of lead administration on developing rat kidney. I. Glutathione S-transferase isoenzymes.

The effects of acute and chronic exposure to lead on glutathione S-transferase (GST) isoforms were determined in developing kidney in the rat. The ontogeny of glutathione S-transferase isoforms was characterized as were the effects of depletion of dietary calcium on glutathione S-transferase isoform profiles in control and lead-treated rats. In the acute exposure experiments, rats of 14 and 50 days of age received three daily injections of lead acetate (114 mg/kg) and in the chronic exposure studies, rats received lead acetate at doses ranging from 50 to 500 ppm in their drinking water. Lead acetate administration in these chronic studies began 1 day after conception. Acute and chronic lead exposure had similar effects, causing increases in all but one glutathione S-transferase isoform (Yb3); these increases were markedly exacerbated by dietary calcium depletion. In all lead paradigms, GST subunits Yb1 and Yp showed the largest increases--greater than 25-fold in rats fed a low-calcium diet. GST subunit Yb3 showed small increases in the 14-day acute lead and the 4 week low-calcium animals and did not increase in other groups. Lead-related increases in GSTs were partially reversed by transferring animals previously receiving lead to lead-free water for a 4-week period. Kidneys of rats fed the low-calcium diet did not have detectable GST Yk, but in rats on this low-calcium diet that received 500 ppm lead; this GST isoform was found at levels comparable to those in control rats fed lab chow.

The effects of lead administration during development on lithium-induced polydipsia and dopaminergic function

Previous studies have demonstrated that postnatal (days 2–29 of life) administration of lead (200 mg/kg/day by gavage) to Long-Evans rats caused permanent increases in lithium-induced polydipsia (LIP) 12. These lead-induced increases in LIP were apparently not of renal origin, did not occur in animals treated with lead after day 30, and persisted for at least 6 months 12,13. The present studies have narrowed the dose-time window for lead-induced increases in LIP. The first study showed that continuous administration of lead (200 mg/kg/day, p.o.) in the form of lead acetate during days 2–9 of life caused increases in LIP ( P = 0.022). Although lead-induced increases in LIP were not statistically significant ( P = 0.084) for the group administered lead from days 9 to 19, the lack of a significant difference between the 2–9- and 9–19-day groups suggested that lead treatment during either of these time periods would result in LIP increases. Lead administration between days 19 and 29 of life was not effective in increasing LIP ( P = 0.8). In the second study, a single dose of lead (200 mg/kg/day) was administered either on day 5 or 15 of life. Concentrations of lead in the blood on day 30 of life averaged 23.2 μg/100 ml for treated rats versus 4.8 μg/100 ml for controls. When tested at approximately 90 days of age, both groups showed significant increases in LIP ( P = 0.028). The rats from this second study were also examined for changes in nigrostriatal dopamine function, since this pathway is known to be essential for LIP 14. After washout of lithium, no differences in the K d or B max of [ 3H]spiperone binding were observed between lead-treated and control groups ( p > 0.4). There were also no differences in the concentrations of dopamine and its acidic metabolites DOPAC and HVA, nor in the ratios of DOPAC or HVA to dopamine ( P > 0.4). Thus, rats with permanent changes in pharmacological sensitivity to lithium have no apparent differences in the characteristics of the unchallenged nigrostriatal dopamine pathway. Whether challenge with lithium should reveal latent differences in these parameters, or whether the nigrostriatal dopamine pathway is not the locus of lead-induced increases in LIP, remains to be determined. In either case, the permanent changes in LIP that may be caused by administration of a single, 200 mg/kg oral dose of lead during the first weeks of life is believed to represent the most sensitive index of lead-induced change in the CNS that has been documented. Since a defined pharmacological probe is used, this should permit elucidation of the involved mechanism(s).