Beneficial effects of aluminum on the progression of lead-induced nephropathy in rats

We studied the effect of aluminum on lead-induced nephropathy in male albino rats. Five groups of male albino rats were given either water only or lead acetate (125 mg/kg body weight) and/or aluminum chloride (50 mg/kg body weight or 100 mg/kg body weight) for a period of 90 days. Aluminum was found to prevent the lead-induced increase in the relative organ (kidney) weight in a dose-dependent manner. Aluminum also prevented lead-induced increase in plasma creatinine levels of the treated animals. Estimation of lead concentration in kidneys of different treatment groups revealed that the net deposition of lead was lower in animals which were given both lead acetate and aluminum chloride simultaneously. The results showed that aluminum offers some protection against lead-induced nephrotoxicity in a time- and dose-dependent manner.     

Antitesticular effect of copper chloride in albino rats

Copper chloride treatment adversely affects testicular activity in albino rats. To investigate its antitesticular effects mature (120 days) Wistar strain albino rats were treated intraperitoneally (i.p.) with copper chloride at doses of 1000, 2000 and 3000 micrograms/kg body weight/day for 26 days. Significant reduction of testicular and accessory sex organs (seminal vesicle, ventral prostate) weight, along with inhibition of testicular delta 5-3 beta-hydroxysteroid dehydrogenase (delta 5-3 beta-HSD) and 17 beta-hydroxysteroid dehydrogenase (17 beta-HSD) activity and reduction in plasma testosterone level, were observed at the doses of 2000 and 3000 micrograms/kg body weight/day. The degree of inhibition in all the parameters were increased with the increase of dosage. But no significant change was observed in the above parameters when the animals were treated with 1000 micrograms/kg body weight/day dose. This suggests that copper produces a suppressive influence on male reproductive activity, mainly on testicular weight and steroidogenesis and accessory sex organ weight in a dose-dependent manner.     

Food flavor cinnamaldehyde-induced biochemical and histological changes in the kidney of male albino wistar rat

Rats were given food flavor cinnamaldehyde (CNMA) orally by gavage at the dose of 2.14, 6.96, 22.62 and 73.5 mg/kg body weight/day for 10, 30 and 90 days. Only the group of rats treated with CNMA at the dose 73.5 mg/kg body weight/day for 90 days showed histological changes in the kidney followed by increased activities of renal, serum and urinary enzymes. CNMA-induced glucosuria in these rats was accompanied by marked proteinuria and creatinuria. Increased serum blood urea nitrogen and serum creatinine and decreased serum protein and glucose levels were observed in these rats. Thus, CNMA at the dose of 73.5 mg/kg body weight/day for 90 days exert its effect on kidney of male albino wistar rat and its effect is time and dose dependent.     

Antihyperglycemic effect of biochanin A, a soy isoflavone, on streptozotocin-diabetic rats

The study was designed to investigate the antihyperglycemic effect of biochanin A on streptozotocin-diabetic rats. Diabetes was induced in adult male albino rats of the Wistar strain, weighing 180-200 g, by administration of streptozotocin (40 mg/kg of body weight) intraperitoneally. Diabetic rats showed increase in plasma glucose and glycosylated hemoglobin and a decrease in plasma insulin and hemoglobin. Activities of gluconeogenic enzymes such as glucose 6-phosphatase, fructose 1,6-bisphosphatase increased and glucokinase, glucose 6-phosphate dehydrogenase decreased in the liver of diabetic rats along with glycogen. Oral administration of biochanin A (10mg/kg body weight) or glibenclamide (600 μg/kg body weight) in 0.5% dimethyl sulfoxide, for 45 days, prevented the above changes and improved towards normality. In addition, protection against body weight loss of diabetic animals by biochanin A was also observed. No significant effect was observed in normal rats treated with biochanin A (10mg/kg bodyweight). These results showed that biochanin A has potential antihyperglycemic activity at a dose of 10mg/kg bodyweight in streptozotocin induced diabetic rats.     

Hepatotoxicity induced by the herbicide atrazine in the rat

The hepatotoxicity of atrazine was investigated by studying clinical parameters related to hepatic function and by electron microscopy. Three groups to male albino rats (Wistar strain) received 100, 200 and 400 mg of atrazine/per kg of body weight/per day, for 14 days. One group received 600 mg atrazine/per kg of body weight/per day, for 7 days. At termination of dosing, the animals were sacrificed and blood was drawn for the determination of serum total lipids, glucose, alanine aminotransferase (ALT) and alkaline phosphatase (SAP). A dose dependent decrease in serum glucose concentration was observed in all the groups. In contrast, a dose relate increase in total serum lipids, was apparent at all dose levels studied. Activity of serum ALT and SAP increased approximately 60% and 200% respectively in rats given 600 mg atrazine/kg bw for 7 days. The liver was examined grossly and microscopically. Electron microscopy disclosed no changes in the hepatocytes of rats treated with the low dose (100 mg/kg bw). At high doses, electron microscopy revealed hepatocytic proliferation and degeneration of smooth endoplasmic reticulum, lipid accumulation and alteration of bile canaliculi proportional to dose and duration of treatment.     

Neuropathologic Findings in Young Male Rats in a Subchronic Oral Toxicity Study Using Triethyl Lead

This study was undertaken to ascertain the neuropathologic effectsof low level exposure of triethyl lead (3EL) to young male rats.Groups of 20 male Sprague—Dawley weanling rats were given3EL at 0, 0.05, 0.10, 0.20, 0.50, and 1.00 mg/kg body wt for91 days, 5 days/week by oral gavage. Lead acetate (PbHOAC) wasgiven at 200 mg/kg body wt/day as a positive control. Animals(five or six) were perfused with glutaraldehyde following barbiturateanesthesia at the termination of the experiment. These animalsand the remaining members of the group received a thorough grossand microscopic postmortem examination. Sections of the central,peripheral, and autonomic nervous systems were examined andlesions scored. No lesions were noted in the brain, but randomlydistributed light microscopic changes of spinal cord Walleriandegeneration were noted to increase in a dose responsive manner(p = 0.48; p < 0.01), with 3EL administration. Ultrastructuralexamination of selected sections of the lumbosacral nerves,revealed lesions characterized by reduced neurofilaments andneurotubules, and irregular lamellated axoplasmic dense bodiesin all animals receiving lead. Organolead was only detectedin animals receiving 3EL, but lead cat- ions were detected inall lead-treated animals. The brain lead levels of 1.00 mg/kg/dayand 200 mg Pb acetate positive control animals were equivalent.As distinctive ultrastructural lesions were seen in all ratstreated with 3EL, we suggest that the no observed adverse effectlevel (NOAEL) for 3EL be lowered to less than 0.05 mg/kg/day.Further studies using lower concentrations of 3EL are requiredto determine the ultrastructural NOAEL, to fully describe thedistribution of the lesions seen and to define the nature ofthe dense bodies.     

Characterization of the effect of deoxynivalenol on selected male reproductive endpoints.

The effect of deoxynivalenol (DON) exposure on male reproductive function was assessed in the rat. Male rats were divided into a control group (n=15 rats) and four treatment groups (0.5 mg/kg, n=15; 1.0 mg/kg, n=15; 2.5 mg/kg, n=15; and 5.0 mg/kg DON, n=16) and exposed to DON daily for 28 days via gastric intubation. Both body weight gain and the final body weight of animals in the 5.0 mg/kg dose group and feed consumption in animals in the 2.5 mg/kg and 5.0 mg/kg dose groups were significantly reduced compared to controls. Fluid consumption was not affected in any of the treated groups. Epididymal and seminal vesicle weights expressed per gram of body weight and brain weight were significantly reduced, compared to control weights, in animals from the 2.5 and 5.0 mg/kg dose groups while prostate weight expressed per gram of brain weight and body weight was significantly lower than controls only in the 5.0 mg/kg dose group. A statistically significant, dose-related decrease in homogenization resistant testicular spermatid counts, spermatid numbers, absolute cauda epididymal sperm numbers and cauda epididymal sperm numbers per gram of cauda epididymis was observed in the 5.0 mg/kg DON treatment group. Sperm tail abnormalities (broken tails) in the 5.0 mg/kg dose group were significantly higher than in the control group. Sperm swimming speed (VSL and VCL) was significantly increased only in the 2.5 mg/kg dose group. Serum FSH and LH concentrations were increased in a dose dependent manner across all treated groups while serum testosterone concentrations were decreased in a dose-related manner across all dose groups. An increase in germ cell degeneration, sperm retention and abnormal nuclear morphology was observed in the 2.5 mg/kg and 5.0 mg/kg dose groups. Treatment related effects included lesions in the non-glandular stomach, thymic lymphoid depletion and splenic hematopoiesis in the 5.0 mg/kg treatment group.     

Peripubertal exposure to low doses of tributyltin chloride affects the homeostasis of serum T,E2, LH,and body weight of male mice

Previous studies have shown that tributyltin could act as an endocrine disruptor in mammals. However, the data on the low‐dose effect of tributyltin in animals are still lacking. The objective of this study was to demonstrate the endocrine disruption induced by low levels of tributyltin chloride (TBTCl) in male KM mice. The animals were treated with 0.05 or 0.5 mg TBTCl/kg body weight/3 days from postnatal days (PNDs) 24 to 45, and killed on PNDs 49 and 84, respectively. Mice treated with 0.5 mg TBTCl/kg exhibited decreased serum and intratesticular testosterone (T) levels on PND 49 and then followed by an obvious recovery on PND 84. Furthermore, mice treated with 0.05 mg TBTCl/kg showed reduced serum 17β‐estradiol (E2) levels on PND 49. However, treatments with TBTCl resulted in a dose‐dependent increase in serum E2 concentration of the mice on PND 84. Administration of TBTCl also decreased levels of serum luteinizing hormone and intratesticular E2 on PND 84. In addition, mice exposed to 0.05 mg/kg TBTCl exhibited an increase in body weight in the late stage of the experiment. These results indicate that treatment with low doses of TBTCl could disturb hormone homeostasis and body weight gain in rodents, and exposure to different levels of TBTCl might have different effects on changing some physiologic parameters. © 2010 Wiley Periodicals, Inc. Environ Toxicol, 2011.     

Effect of tetraethyl lead and restricted food intake on locomotor activity in the rat

The effect of tetraethyl lead (TEL) and restricted food intake on spontaneous locomotor activity in male albino rats was investigated. Forty animals were injected intraperitoneally with 4, 7, 10 or 13 mg/kg body weight of TEL in peanut oil, or a peanut oil placebo. Forty additional animals were food yoked to lead treated animals as a control procedure to hold food intake constant between lead treated and lead free animals. A comparison of pre- and posttreatment measures revealed significant decreases in food intake and increases in activity levels at dosages of 7, 10 and 13 mg/kg of TEL. In addition, food intake and activity were significantly correlated in both lead treated and yoked groups. The issue of factors associated with reduced food intake playing a role in observed activity level increases was raised.     

Amelioration of lead toxicity on rat liver with Vitamin C and silymarin supplements

The aim of the present study was to investigate the impact of the combined administration of Vitamin C and silymarin on lead toxicity. Male albino rats were subdivided into three groups: the first was a control group, the second received lead acetate in diet as 500 mg/kg diet daily, the third received the same lead acetate dose and supplemented with Vitamin C (1 mg/100g body weight) and silymarin (1 mg/100g body weight) by gastric tube three times per week. Blood samples were taken after 2, 4 and 6 weeks of treatment. Significant lead-induced elevations in serum ALT, AST, GGT and ALP activities were observed after different periods of treatment. However, serum LDLc was decreased. The intensities of RNA and apoptotic fragments of DNA were measured as optical density by Gel-pro program. Lead acetate decreased the intensity of DNA at 6 weeks and induced apoptotic DNA fragments reversibly with time. After 2 weeks of lead administration dilation and congestion of terminal hepatic veins and portal vein branches were observed. Lead also induced hepatocyte proliferation without any localized distribution among zones 1-3. Portal inflammatory infiltrate with disruption of the limiting plates (interface hepatitis), steatosis, apoptosis and mild fibrosis were detected especially by sixth week of lead administration. Combined treatment of lead-exposed animals with Vitamin C and silymarin showed marked improvement of the biochemical, molecular and histopathological findings. These experimental results strongly indicate the protective effect of Vitamin C and silymarin against toxic effects of lead on liver tissue.     

Behavioral effects of repeated aluminum administration in the rat.

Behavioral effects of repeated aluminum administration during prenatal periods were studied in THA rats. Four groups of pregnant rats were administered a daily dose of 0, 90, 180 or 360 mg/kg of aluminum chloride from the 8th day to 20th day of gestation by gavage. No differences were observed between the aluminum treated offspring and controls in terms of body weight. Delays in pivoting, longer latency and more rearings in an open field test were observed in the 360 mg/kg treated group, but no other developmental alterations were found. Urination in the open field test in the 180 mg/kg and 360 mg/kg treated groups was significantly more frequent than in the other two groups of rats. These results suggest that repeated doses of aluminum chloride during the prenatal period affects neuromotor maturation and emotionality in rats.     

A 28-day feeding study with methyl isoeugenol in rats.

Methyl isoeugenol was administered in rodent diet for a minimum of 28 consecutive days to groups of 16 male and 16 female rats (Sprague-Dawley strain) at levels of approximately 30, 100 and 300 mg/kg body weight/day. A further group of 16 male and 16 female rats was given the rodent diet as a control. The administration of methyl isoeugenol in the diet did not adversely affect the growth or general health of the animals or their food intakes. Although high dose animals of both sexes had increased lymphocyte and total white blood cell counts, these are not considered, in isolation, to be an adverse effect of treatment. None of the minor variations observed in the serum chemical analyses or urine analyses is considered to be indicative of a treatment-related toxic effect. An increase in liver weight, adjusted for body weight, was seen in male and female rats receiving 300 mg methyl isoeugenol/kg body weight. Few histopathological abnormalities were observed. Although the incidence of kidney and Harderian gland lesions was higher for high dose animals compared with the controls, the lesions are of a type that occurs spontaneously and are thus not considered to be attributable to treatment with methyl isoeugenol. While the increased liver weight and white blood cell counts of rats given 300 mg methyl isoeugenol/kg body weight may represent effects of treatment, it is not considered that there is any reason to regard these as adverse effects.     

Co‐exposure to aluminum and acrylamide disturbs expression of metallothionein,proinflammatory cytokines and induces genotoxicity: Biochemical and histopathological changes in the kidney of adult rats

The individual toxic effects of aluminum and acrylamide are known but there is no data on their combined effects. The present study investigates the toxic effects after combined exposure to these toxicants on: (i) oxidative stress during combined chronic exposure to aluminum and acrylamide on kidney function (ii) correlation of oxidative stress with metallothionein (MT) and inflammatory cytokines expression, DNA damage, and histopathological changes. Rats were exposed to aluminum (50 mg/kg body weight) in drinking water and acrylamide (20 mg/kg body weight) by gavage either individually or in combination for 3 weeks. Exposure rats to aluminum chloride or acrylamide alone and in combination induced nephrotoxicity, as evidenced by a decrease in the 24‐h urine volume and uric acid levels in plasma and an increase of plasma creatinine, urea, and blood urea nitrogen levels. Nephrotoxicity was objectified by a significant increase in malondialdehyde level, advanced oxidation protein, and protein carbonyl contents, whereas reduced glutathione, nonprotein thiol, vitamin C levels, catalase, and glutathione peroxidase activities showed a significant decline. Superoxide dismutase activity and its gene expression were increased. Aluminum and acrylamide co‐exposure exhibited synergism in various biochemical variables and also in DNA damage. Kidney total MT levels and genes expression of MT1, MT2, and proinflammatory cytokines were increased. All these changes were supported by histopathological observations. Co‐exposure to aluminum and acrylamide exhibited synergism and more pronounced toxic effects compared with their individual effects based on various biochemical variables, genotoxic, and histopathological changes. © 2015 Wiley Periodicals, Inc. Environ Toxicol 31: 1044–1058, 2016.     

Effect of Zingiber officinale on some biochemical parameters and cytogenic analysis in lead-induced toxicity in experimental rats

Exposure to toxic elements is greatly unavoidable in our daily activities due to several routes of coming in contact with these elements. Thus lead (Pb), is one of the major causes of health hazard in human. In this study, evaluation of Zingiber officinale as mitigating measure against Pb induced biochemical and cytogenic toxicity in albino rats was investigated. Experimental rats were grouped into five with five animals per group, group I serves as control and groups 2–5 were induced intraperitoneal with lead acetate dissolved in distilled water at 3?mg/kg body weight whereas group 3–5 were orally administered with 200?mg/kg vitamin C, 200?mg/kg, and 100?mg/kg of Z. officinale, respectively for 7 d. The obtained results show that aspartate aminotransferase (AST), alkaline phosphatase (ALP), lipid peroxidation, urea, creatinine, bilirubin, and gamma-glutamyl transferase (GGT) were significantly increased (p?p?p?Z. officinale. Hence, these results suggest that Z. officinale roots might contain therapeutic potential that can ameliorate the hazard effect of lead acetate poison.     

Target Organ Toxicity and Leukopenia in Fischer 344 Rats Given Intravenous Doses of Vinblastine and Desacetyl Vinblastine

Target Organ Toxicity and Leukopenia in Fischer 344 Rats GivenIntravenous Doses of Vinblastine and Desacetyl Vinblastine.ZIMMERMANN, J. L., TODD, G. C., AND TAMURA, R. N. (1990). FundamAppl Toxicol 17, 482–493. The toxicity and leukopeniaproduced by vinblastine or desacetyl vinblastine were establishedin 1-month studies in rats. Groups of male Fischer 344 ratswere given weekly intravenous doses of vinblastine or desacetylvinblastine at doses of 0.08, 0.16, 0.32, 0.64, or 1.28 mg/kg.The target organ toxicity was similar for both compounds. Decreasedcell production in the thymus, testes, and bone marrow was producedin the animals of the two highest dose groups for both compoundswith the degree of seventy greater in the highest dose group.All high dose rats (1.28 mg/kg) given desacetyl vinblastineand three rats given vinblastine died prior to study termination.Body weight loss was more pronounced in high dose rats givendesacetyl vinblastine, but at lower doses there were no significantdifferences in body weight reduction for rats receiving eithercompound. Leukopenia occurred at all dose levels of 0.32 mg/kgand higher. During the first 2 weeks of the study, rats given1.28 mg/kg of desacetyl vinblastine had a greater leukopenicresponse than rats given 1.28 mg/kg of vinblastine. It is concludedthat both compounds produced similar target organ toxicity andleukopenia without deaths at doses of 0.32 and 0.64 mg/kg givenonce a week for 4 weeks. At the high dose (1.28 mg/kg) desacetylvinblastine was more toxic than vinblastine resulting in greatermortality and body weight reduction.     

Maximal Tolerated Daily Doses of Dicophane

Dicophane was given by intragastric cannula to young male albino rats in daily doses of from 43 to 250 mg/kg for 100 days or until 90 % of the animals had died. The LDO (100 days) or maximal dose which killed no animals when given daily for 100 days was 42.8 ± 1.6 mg/kg/day, the LD50 (100 days) was 64.8 ± 1.4 mg/kg/day and the minimal LD100 (100 days) was 97.1 ± 2.8 mg/kg/day. The 100-day LD50 index, or the LD50 (100 days) expressed as a percentage of the acute, oral LD50 (1 dose) was 17.6 ± 0.4. During the first 21 days of administration, the clinical signs of intoxication were similar to those recorded in studies on acute toxicity with single lethal doses. Clinical signs in 21 day-survivors were limited to polydipsia, diuresis, aciduria, and some loss of body weight. Autopsy at 100 days revealed degenerative changes in the kidneys, liver and testes, a stress reaction, hypertrophy of the liver and gastrointestinal organs, and capillary congestion and loss of weight (with variable changes in water content) of many body organs. The 100-day multiposal (subacute, chronic) toxicity of dicophane was similar to that of non-narcotic analgesics such as aspirin, phenacetin and paracetamol.     

氯化锂对染铅大鼠体重及学习记忆的影响

目的探讨氯化锂对染铅大鼠体重和学习记忆能力的影响,进一步阐明锂对铅神经毒性的拮抗效应及其可能机制。方法将大鼠随机分为对照组、染铅组和4个铅 氯化锂(3、30、300和3 000 mg/kg)组,分别给予普通饲料和含氯化锂(3、30、300和3 000 mg/kg)的饲料喂养60 d,通过测量体重和Y-迷宫实验,采用NADPH-d组织化学染色,观察各组大鼠之间体重增量,学习记忆能力和大脑皮层一氧化氮合酶(NOS)阳性细胞数的差别。结果染铅组大鼠体重增量低于对照组,Y-迷宫实验学会次数高于对照组(P<0.01);铅 氯化锂(3和30 mg/kg)组大鼠体重较染铅组大鼠增长多(P<0.01),铅 氯化锂(3、30和300 mg/kg)组Y-迷宫学会次数均低于染铅组大鼠(P<0.01)。染铅组皮层NOS阳性细胞数较正常大鼠明显减少(P<0.05);与染铅组比较,铅 氯化锂(3、30、300和3 000 mg/kg)组皮层NOS阳性细胞数均显著性增多(P<0.05)。结论锂能明显促进染铅大鼠体重的增加和学习记忆能力的增强,锂对铅的神经毒性有一定拮抗作用。     

Absorption and Retention of Aluminum from Drinking Water: 1. Effect of Citric and Ascorbic Acids on Aluminum Tissue Levels in Rabbits

Absorption and Retention of Aluminum from Drinking Water. 1.Effect of Citric and Ascorbic Acids on Aluminum Tissue Levelsin Rabbits. FULTON, B., AND JEFFERY, E. H. (1990). Fundam. Appl.Toxicol. 14, 788–796. Adult, male New Zealand rabbits(three per group) were administered drinking water containingaluminum chloride (0, 100, or 500 mg Al/liter) together withcitrate (0.11 m), ascorbate (0.11 M), or no added ligand adlibitum for 12 weeks. They were fed ad libitum regular rabbitchow analyzed to contain 297 mg Al/kg. Treatment had no effectupon food and water intake or weight gain during the experimentalperiod. No effect of aluminum was observed on tissue levelsof the essential metals zinc, copper, and iron, or on hemoglobinand hematocrit values. Aluminum levels were found to increasein a dose-dependent manner in stomach and intestinal mucosa,kidney, bone, urine, and feces. There was only a slight accumulationin liver, and no accumulation in brain (cerebral cortex or hippocampus).Although plasma aluminum was directly related to aluminum intake,whole blood aluminum bore no relation to aluminum dose. Citratehad no effect on aluminum accumulation in the stomach or intestine,but significantly enhanced plasma and bone aluminum levels.Ascorbate did not enhance aluminum accumulation in any tissuestudied and even prevented accumulation in bone. Both citrateand ascorbate enhanced excretion of aluminum. Ascorbate therapymay be of potential clinical use to enhance aluminum excretion.     

Evaluation of the maternal and developmental toxicity of aluminum from high doses of aluminum hydroxide in rats

The potential of aluminum hydroxide [Al (OH)3] to induce developmental toxicity in rats was evaluated in the present study. Al (OH)3 was given by gavage at dose levels of 192, 384, and 768 mg/kg/day to groups of pregnant rats from day 6 through day 15 of gestation. Control animals received distilled water. Pregnant rats were evaluated for body weight, weight gain, food consumption, appearance, behavior and reproduction data. Cesarean sections were performed on gestation day 20, and the fetuses were removed for teratological evaluation. No significant maternal or developmental toxicity was observed at any Al (OH)3 dose level. Consequently, the no-observed-effect level (NOEL) for Al(OH)3 maternal or developmental toxicity would be greater than or equal to 768 mg/kg/day, which was the highest dose tested. This dose would be equivalent to a 60 kg person ingesting 16 g Al/day.