Injection Of Lead Acetate Research Articles

Remodeling of cancellous bone in young monkeys.

Remodeling of the trabeculae in cancellous bone was studied in young monkeys that received multiple weekly injections of lead acetate as a marker. Resorption of old bone and deposition of new bone were demonstrated. The rate of deposition of new bone varied at different sites of the same trabeculae and also at different time intervals of the same site. The total formation time of new bone to fill the trabecular space was estimated.

Effects of lead on the induction of hepatic microsomal enzymes by phenobarbital and 3,4-benzpyrene

A single ip injection of lead acetate (65 mg/kg) prolonged the duration of zoxazolamine paralysis in Sprague-Dawley rats and prevented the stimulation of zoxazolamine metabolism normally induced by phenobarbital. Lead also delayed the phenobarbital induction of hepatic microsomal cytochrome P-450 at 12 and 24 hr after treatment. However, the inhibitory effect of lead had disappeared and cytochrome P-450 concentrations were markedly elevated at 48 hr. Lead also diminished hepatic microsomal cytochrome P-448, normally resulting from benzyprene treatment. Neither lead, phenobarbital, benzyprene nor their combination had a significant effect on hepatic cytochrome b 5 values. Lead, in vitro, inhibited the hepatic microsomal NADPH-cytochrome c and P-450 reductase activity in a dose-dependent manner. In vivo, significant inhibition of NADPH-cytochrome c and P-450 reductase activity was observed after the injection of lead acetate. Significant inhibition coincides with the time when lead concentration in the hepatic microsomes was maximal. The inhibition of δ-aminolevulinic acid dehydratase (ALAD) activity at several blood lead concentrations was confirmed both in vivo and in vitro. This relationship between blood lead concentrations and ALAD activity was not altered by pretreatment with phenobarbital or benzpyrene.

Effects of simultaneous administration with cadmium and lead on the essential minerals and on the drug-metabolizing enzyme systems in rats (author's transl)

Essential metal contents and the liver microsomal drug-metabolizing enzyme systems were investigated in rats treated simultaneously with cadmium chloride and lead acetate. 1) Calcium content in the liver increased markedly both by a single injection of lead acetate and by simultaneous administration of lead acetate and cadmium chloride, and this increase was observed even after 30 days. 2) Zinc content in the liver increased significantly 1 and 3 days for male rats and 3 days for female rats after a single administration of cadmium chloride. Copper content in the kidney also increased 15 days after the injection of cadmium chloride. 3) Content of δ-aminolevulinic acid in urine increased markedly by the injection of lead acetate and this increase was still noted after 30 days. 4) Of the fatty acid constituents in the liver phospholipids, stearic acid increased, and arachidonic acid decreased by the treatment with cadmium chloride and/or lead acetate. 5) Content of cytochrome P-450 and b5, as well as activities of aniline hydroxylase and aminopyrine demethylase, decreased markedly by the administration of cadmium chloride and/or lead acetate.

Action of parathyroid hormone, with special reference to its anabolic effect on different kinds of tissues in rats (I).

The effect of parathyroid hormone (PTH) on the spongiosa of the proximal tibia and the alveolar bone in immature rats was studied using a time marker by the injection of lead acetate. 1) When intact rats were fed on a low calcium diet, the promotion of the apposition of the alveolar bone and the longitudinal formation as well as the resorption of the spongiosa were observed, but no change was detected in the serum calcium level. The resorption was more remarkable than the formation. 2) By parathyroidectomy (PTX) or thyroparathyroidectomy (TPTX) the effect described in 1) disappeared completely, but there subsequently occurred a fall of the serum calcium level and a marked inhibition of the formation and resorption. The decrease in the appositional formation was stronger than in the longitudinal formation. 3) When PTH was injected into the rats having undergone PTX or TPTX, all of the effects in 2) were reversed with the recovery of the apposition being at an extremely high rate. All the foregoing results indicate that PTH has an evident anabolic action in addition to the action of increasing the bone resorption and that the sensitivity to PTH is stronger in the periosteal bone than in the spongiosa.

The equilibration of lead between blood and milk of lactating rabbits

The basal concentration of lead in milk of lactating rabbits is approximately 65% that of blood. After the intravenous injection of lead acetate, the lead concentration in blood peaked at 1 hour and thereafter declined rapidly, reaching a plateau within 5 days. In contrast, the lead concentration in milk continuously increased with time and by 7.5 days (maximum) exceeded that of blood 8-fold. The possibility that passage of Pb ++, like Ca ++, Sr ++ and other ions from blood to milk occurs against a concentration gradient is suggested. The consequences of this observation on subclinical lead poisoning in neonates is discussed.

Mechanism of induction of hypercalcemia and hyperphosphatemia by lead acetate in the rat.

The present study is an investigation of the mechanism of hypercalcemia and hyperphosphatemia induced by the intravenous injection of lead acetate (Pb-Ac). A total of 118 male rats were injected with 30 mg/kg of Pb-Ac, or with 16.5 mg/kg of sodium acetate as the control. The levels of serum calcium, phosphorus and lead were then determined at various time periods after the injections. Serum calcium and phosphorus levels increased with time after Pb-Ac injection and the maximum values of calcium (17 mg%) were found after 1 h and of phosphorus (13.5 mg%) after 30 min. Both calcium and phosphorus levels reverted to the normal range after 12 h. The maximum net rates of increase of calcium and phosphorus were found immediately after Pb-Ac injection. At that time, deposition of lead at the calcifying sites of bone and incisor dentin was demonstrated by a histochemical examination. In other experiments the changes in the calcium and phosphorus contents in the medium after shaking bone powder in serum with Pb-Ac in an in vitro system were studied. It was confirmed that the calcium and phosphorus were displaced from the bone mineral, the extent of the displacement being correlated with the concentration of the Pb-Ac added to the medium, and that these displacements were very rapid reactions. These results suggest that hypercalcemia and hyperphosphatemia following Pb-Ac injection results from a direct action of lead on the bone mineral.

Effects of Repeated Ingestion of Large Quantities of Acetylsalicylic Acid on Membranous Bone Growth and Dentin Apposition in Young Monkeys

Four daily doses of ASA were administered by mouth to young growing monkeys which received six injections of lead acetate every seven days as an intravital stain to indicate sites of bone and dentin mineralization. Microscopic evaluation of the inhibitory effects on membranous bone growth and dentin apposition was made. Four doses of ASA at 325 mg/kg inhibited membranous bone growth as well as the remodeling of the Haversian canal systems for about 16-18 days, with incomplete recovery during the experimental period. No comparable effect on dentinogenesis was observed. This preliminary study indicates that four doses of ASA at this level caused a toxic effect directly on membranous bone growth but not on dentin apposition.

Remodeling of compact bone studied with lead acetate as an intravital stain.

Remodeling of the osteons or Haversian canal system in compact bone was studied in young monkeys that received serial injections of lead acetate as an intravital strain. The successive stages of the formation of an osteon have been demonstrated. The rate of the filling of the lamellar bone decelerated as the lumen of the Haversian canal decreased. The total formation time of individual osteons was estimated.

Stimulated DNA synthesis in livers and kidneys induced to proliferate associated with unchanged thymidine and thymidylate kinase activities

Enhanced mitotic activity and stimulated DNA synthesis associated with unchanged activity of thymidine and thymidylate kinases were observed in mouse kidneys induced to proliferate by intracardiac injection of lead acetate, and in rat livers following repeated administration of 5-azacytidine. On the other hand, the enhanced thymidine kinase activity evoked by l-tryptophan given by intubation at later stages of liver regeneration was paralleled by the enhanced incorporation of thymidine into DNA only to a very small degree.

Protective effect of sclerin on a lead-acetate injury affecting the growth and porphyrin metabolism in rat.

While a continuous ingestion of lead acetate added in drinking water suppressed the rat growth, depressing in some degree the level of hepatic δ-aminolevulinate (ALA) dehydratase, a very small amount of sclerin (SCL) added simultaneously in the water restored the growth and dehydratase level. Moreover, subcutaneous injection of SCL to the rat not only maintained the ALA dehydratase level, but prevented a marked depression of the level of mitochondrial ALA synthetase in liver caused by intraperitoneal injection of lead acetate. Injection of SCL alone increased tolerably (about 1.8 times) the mitochondrial ALA synthetase, but little the extramitochondrial synthetase. The treatment by SCL was attended by a initial decrease, then a gradual increase in the activity of microsomal drug metabolizing enzyme.

Letter: "Swiss-cheese" platelets.

Comments and Corrections1 December 1974"Swiss-Cheese" PlateletsJORGE E. MALDONADO, M.D., PH.D., F.A.C.P.JORGE E. MALDONADO, M.D., PH.D., F.A.C.P.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-81-6-860_2 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptTo the editor: Two reports (1, 2) have recently appeared in the Annals of Internal Medicine concerning platelets with a widely dilated open canalicular system and the ultrastructural appearance described by the term "Swiss-cheese" platelets. In the first paper (1), a patient with a mild bleeding tendency had giant and vacuolated platelets. Initially this patient had laboratory features of thrombasthenia, with later changes more consistent with thrombopathia. More recently, Davis (2) reported that Swiss-cheese platelets could be induced experimentally in rats by injection of lead acetate, and he illustrated similarly vacuolated platelets from a case of familial thrombocytopenia.In electron...

Bone marking and lead intoxication. Early pathological changes in osteoclasts.

Hitherto osteoclasts have not been studied in relation to lead intoxication after a single intravenous lead acetate injection. In this study a dose of no more than 4 mg/kg body weight provoked the origin of characteristic nuclear as well as cytoplasmic inclusion bodies. The individual bodies consist of a dense homogeneous core with an equally dense or less dense fibrillar periphery. Irregularly shaped aggregates of cytoplasmic bodies were also found. The persistence of nuclear bodies over cytoplasmic bodies, is discussed.

Effects of tetracyclines on membranous bone growth and dentin apposition in young rhesus monkeys.

Various tetracyclines were administered by different routes to young monkeys that received multiple injections of lead acetate as an intravital stain of calcification sites. Microscopically, the tetracyclines inhibited membranous bone growth, but they did not affect dentin apposition.

Lead pica produced in rats.

Weanling rats eating a low calcium diet voluntarily ingested lead acetate solutions in much greater proportions than did iron-deficient or control weanlings. This increased ingestion occurred even with high concentrations of lead acetate which normal weanlings found extremely aversive. Chronic injections of lead acetate into weanlings did not change lead ingestion, indicating an absence of behavioral regulation of body lead levels. Female lead-injected weanlings did show a significant increase in calcium ingestion. Calcium deficiency may be one component of lead pica.

Mechanism of the heterotopic calcification induced by subcutaneous injection of lead acetate.

Mechanism of the heterotopic calcification induced by subcutaneous injection of lead acetate.

Preliminary Study of Inhibitory Effects of Tetracyclines on Membranous Bone Growth in Rhesus Monkeys

Various doses and forms of tetracycline were administered to young monkeys that received multiple injections of lead acetate as a vital marker of the calcification sites. The effects of these tetracyclines on membranous bone growth were assessed histologically ; retarded bone growth occurred under some conditions.

Reticuloendothelial and hepatic functional alterations following lead acetate administration

The influence of a single intravenous injection of lead acetate on the phagocytic activity of the reticuloendothelial system (RES) and on endotoxin-detoxifying ability of liver and spleen homogenates was studied in an effort to delineate the mechanism by which lead enhanced host sensitivity to endotoxin. Lead acetate administered to rats induced a state of phagocytic depression as indicated by an impaired intravascular phagocytosis of colloidal carbon. The employment of the 131I-triolein-labeled lipid emulsion to determine phagocytic alterations in leadtreated animals indicated a lead-induced impairment in hepatic phagocytosis. Liver and spleen homogenates prepared from normal or control rats possessed significant endotoxin-detoxifying ability as bioassayed in actinomycin D-treated mice. Lead acetate significantly reduced the ability of liver and spleen to detoxify endotoxin. Hepatic parenchymal cell function was also deranged by lead administration as indicated by an increased plasma retention of bromsulphalein and an elevated unconjugated bilirubin, serum alkaline phosphatase and glutamic oxaloacetic transaminase. These results demonstrate that while lead acetate induces endotoxin hyperreactivity by impairing the phagocytic as well as the endotoxin-detoxifying properties of macrophages, hepatic parenchymal cell dysfunction may also be a contributing factor. These findings accent the importance of hepatic functional status in host defense against endotoxin as well as the ability of lead to induce acute hepatic injury.

Interferon Production Linked to Toxicity of Polyriboinosinic Acid-Polyribocytidylic Acid

Different procedures have been used in attempts to increase the production of interferon by polyriboinosinic acid-polyribocytidylic acid (poly [rI].poly [rC]) in mice: simultaneous injection of lead acetate, cycloheximide, or actinomycin D and prior injection of Freund's adjuvant, chlorite-oxidized oxyamylose (COAM), endotoxin, or Brucella abortus. In the experimental conditions tested, lead acetate, cycloheximide, Freund's adjuvant, and COAM brought about a parallel increase in interferon production and toxicity (lethality) of poly (rI).poly (rC); actinomycin D, endotoxin, and B. abortus increased the lethality of poly (rI).poly (rC) without a concomitant raise of its interferon-inducing capacity. Our results indicate that no significant increase in interferon production (or antiviral activity, as far as the antiviral activity is accounted for by interferon production) without an accompanying increase in toxicity can be achieved with poly (rI).poly (rC) and that it might be impossible to increase its therapeutic ratio (ratio of maximum tolerated dose to minimum effective dose).

Effects of some staining agents on dentin apposition in young rabbits.

Alizarin red S, trypan blue, chlortetracycline, and 45Ca were administered to young rabbits that received multiple injections of lead acetate as marker. Inhibiting effects of these agents on dentin apposition were studied. No evidence of toxicity of chlortetracycline or 45Ca was detected. Alizarin at 100 mg/kg reduced the rate of dentin apposition, and 150 mg/kg caused severe retardation. Trypan blue at 50 to 100 mglkg showed no adverse effects, but 350 mglkg arrested dentinogenesis completely.

Eight nerve in experimental lead poisoning.

Forty healthy guinea pigs were poisoned with repeated peritoneal injections of lead acetate. After 7 weeks the animals were sacrificed and the inner ear with VIII nerve were examined histologically. The lead level in the blood was estimated in all animals after poisoning and in 10 healthy guinea pigs (control group). The sensory cells of the inner ear, the spiral and vestibular ganglion cells appeared to be normal. The VIII nerve in the majority of poisoned animals showed segmental deniyelina-tion and axonal degeneration. Theories on etiology and pathogenesis of the neuropathological changes in lead poisoning are discussed.