Biochemical, haematological and histopathological study in relation to time-related cadmium-induced hepatotoxicity in mice

In the present investigation sub-chronic hepatic necrosis was induced by cadmium chloride and was examined biochemically, haematologically and histopathologically in order to study the time-dependent effect and correlation among the parameters. Male balb/c mice were injected with cadmium chloride (2.5 mg/kg bw s.c.) for each other day and, sacrificed on the 7th day, 14th day and 21th day post exposure. Body weight and relative liver weight did not show alteration at any of the time point following the treatment but the tissue cadmium level showed progressive significant increment values with the advancement of time exposure. Most of the biochemical parameters (total protein, DNA, RNA, cytochrome P450 cotents, alkaline phosphatase and UDP glucuronyl transferase activities), haematological parameters (total red blood cells, total white blood cell, differential white blood cell counts, haemoglobin, erythrocyte sedimentation rate, serum glutamic oxaloacetic transaminase, serum glutamic pyruvic transaminase, plasma protein) indicated either no or less on the alterations/7th day following cadmium exposure. Both the light and transmission electron microscopy, on the other hand, indicated the fact that a minimum of 21 day-exposure was needed to alter the cellular architecture. So, a certain amount of cadmium load might be required to adversely affect the cellular architecture preceeded by biochemical and haematological alterations. In this connection, in the present study a possible mechanism of cadmium-induced hepatoxicity was discussed.     

Hepatoprotective activity of Leucas hirta against CCl4 induced hepatic damage in rats

Methanol and aqueous leaf extracts of L. hirta demonstrated hepatoprotective activity against carbon tetrachloride induced liver damage in rats. The parameters studied were serum total bilirubin, total protein, alanine transaminase, aspartate transaminase and alkaline phosphatase activities. The hepatoprotective activity was also supported by histopathological studies of liver tissue. Results of the biochemical studies of blood samples of CCl4 treated animals showed significant increase in the levels of serum markers and decrease in total protein level reflecting the liver injury caused by CCl4. Whereas blood samples from the animals treated with methanol and aqueous leaf extracts showed significant decrease in the levels of serum markers and increase in total protein indicating the protection of hepatic cells. The results revealed that methanol leaf extract followed by aqueous extract of L. hirta could afford significant protection against CCl4 induced hepatocellular injury.     

Comparative study on the inhibition of acetylcholinesterase activity in the freshwater fish Cyprinus carpio by mercury and zinc.

The effects of sublethal concentrations of mercury (0.1mg/l) and zinc (6 mg/l) on acetylcholinesterase activity and acetylcholine content of gill, kidney, intestine, brain, liver and muscle of the freshwater fish Cyprinus carpio at 1, 15 and 30 days of exposure were studied. A significant suppression in acetylcholinesterase activity was recorded in all the organs from both mercury and zinc intoxicated fish at all the exposure periods. Concurrently, a significant increase in the content of acetylcholine in the organs was observed. These changes observed in the organs of mercury treated fish in different exposure periods were in the order 1 greater than 15 less than 30 days and in zinc treated fish 1 greater than 15 greater than 30 days. Further, these changes were greater in magnitude in the brain, liver and muscle (non-osmoregulatory organs) than in the gill, kidney and intestine (osmoregulatory organs) in both metal media.     

Toxicity of Microcystis aeruginosa K-139 strain

Toxicity of the cells of a newly established axenic Microcystis aeruginosa K-139 strain to mice was studied. LD50 of the cells harvested in the mid-log phase was 7.3 mg/kg. The organs of acute dead mice were examined histopathologically. The blood congestion and necrosis of the parenchymal cells around the central veins in the liver were observed, but other organs seemed to be normal. The liver damage was confirmed by the tests of glutamic oxaloacetic transaminase (GOT) and glutamic pyruvic transaminase (GPT) activities in the sera of the mice after the injection with the K-139 cells. Furthermore, the K-139 cells were capable of inducing interleukin 1 (IL-1) production by peritoneal macrophages in vitro.     

Toxicity of pure alkaloid of Tylophora asthamatica in male rat

Administration of pure alkaloid of T. asthamatica, suspended in peanut oil and given in single doses (12-100 mg/kg) by gavage, to male rats caused inactivity, respiratory distress, salivation, nasal discharge and diarrhoea. The oral LD50 value of the alkaloid was 35.32 mg/kg. In short term toxicity study daily doses of the alkaloid (1.25, 2.5, 5 and 10 mg/kg) were given to male rats for 15 days. Smaller doses of the alkaloid (1.25 and 2.5 mg/kg/day) produced no signs of poisoning or death in animals; while 5 mg/kg/day produced signs of poisoning and death of two animals, 10 mg/kg/day caused death of all the animals within 7 days. Activities of glutamic oxaloacetic transaminase, glutamic pyruvic transaminase and alkaline phosphatase were significant and associated with morphological changes in liver. The alkaloid also caused marked changes in the morphology of seminiferous tubules and spermatogenic activity of experimental animals. Since the alkaloid is effective in microgram quantities, the non toxic effects observed after daily doses of 1.25 mg/kg in male rats assume great therapeutic significance.     

Effect of chronic exposure to static magnetic field upon the serum glutamic pyruvic transaminase activity GPT and morphology of the cardiac muscle, skeletal muscles, kidneys, cerebellum and lung tissue in guinea pigs

In a cycle of investigations concerning the pathogenesis of functional changes caused by the influence of magnetic field of induction occurring in laboratory and industrial conditions glutamic pyruvic transaminase activity in external blood and morphological picture of cardiac muscle, skeletal muscles, kidneys, cerebellum and lung tissue in guinea pigs were examined. Static homogeneous magnetic field as low as 0.005 T produced a statistically significant decrease in GPT activity. The animals were exposed to the magnetic field action for seven weeks 1 hour a day, 7 days a week. The range of observed changes of enzyme activity were determined by the duration of magnetic field. No morphological changes were observed.     

Effects of an organophosphate pesticide, quinalphos, on the hypothalamo-pituitary-gonadal axis in adult male rats

The effects of chronic sub-lethal doses (7-14 mg kg-1 a day for 15 days) of quinalphos were evaluated in adult male rats for changes in testicular morphology, circulatory concentrations of hormones (LH, FSH, prolactin and testosterone), activities of acetylcholinesterase (AChE) and angiotensin converting enzyme (ACE) as well as metabolism of biogenic amines (dopamine, noradrenaline and 5-hydroxytryptamine (5-HT)) in the hypothalamus and pituitary. Hormones were assayed by radioimmunoassay or chemiluminescent immunoassay (testosterone). The enzymes were estimated after spectrophotometry and the biogenic amines by HPLC-electrochemistry. Sub-lethal chronic administration of quinalphos resulted in: decreased testicular mass and AChE activity in central as well as peripheral organs; increased serum LH, FSH, prolactin and testosterone concentrations; decreased pituitary or increased testicular ACE activity; severe disruption of spermatogenesis with increasing doses of pesticide; and no significant effects on dopamine, noradrenaline or 5-HT concentrations in the hypothalamus or pituitary. Administration of oestradiol (50 micrograms per rat a day) during pesticide treatment resulted in: a significant decrease in the mass of the testis and accessory sex organs; decreases in serum LH, FSH, testosterone concentrations; an increase in prolactin concentration; and a decrease in dopamine or an increase in noradrenaline and 5-HT in the hypothalamus or pituitary. Oestradiol had a marked effect: in pesticide-treated animals, the pesticide effects were significantly reversed. This indicates that in pesticide toxicity, the hypothalamo-pituitary-gonadal axis is operational. Since many of the observed pesticide effects could be inhibited by oestradiol, it is suggested that the pesticide acts directly on the gonadotrophins. In conclusion, quinalphos decreases fertility in adult male rats by affecting the pituitary gonadotrophins.     

Effect of static magnetic field on some enzymes activities in rats

The magnetic field of 0.008 T and 0.15 T inductions influence lasting 7 weeks (7 days a week), 1 h daily determines the increase of the activity of cytoplasmatic enzymes (glutamic pyruvic transaminase, glutamic oxalacetic transaminase, lactic dehydrogenase), the decrease of cholinesterase activity and the growth of alkaline phosphatase activity in the plasma of the examined animals. The observed changes were reversible. 2 months after the exposure had been stopped, the tested parameters were back to normal.     

微量元素锌和超氧化物歧化酶对产蛋鸡影响的研究

结果表明：与对照相比,加锌Ⅱ组鸡的产蛋率高（P＜0．05）,破壳率低（P＜0．01）;加锌Ⅱ组鸡的产蛋率高（P＜0．01）,破壳率降低（P＜0．01）,蛋重增加（P＜0．05）饲料消耗减少,Ⅱ组与Ⅲ组比较,生产性无显著差异。Ⅱ组和Ⅲ组肝中GOT和GPT、血清中AKP酶活性显著增加（P＜0．01）肝中AKPⅡ组明显上升（P＜0．05）,Ⅲ组显著提高（P＜0．01）,SOD酶活性Ⅱ明显增加（P＜0．05）,Ⅲ组显著上升（P＜0．01）,Ⅱ组与Ⅲ组比较,肝中GOT和AKP存在显著差异（P＜0．01）。其它酶活性各组间无明显差异（P＜0．05）。鸡蛋中的锌含量Ⅱ和 Ⅲ组大幅度上升（P＜0．01）,Ⅲ组磷脂降低（P＜0．05）,Ⅱ组不受影响（P＜0．05）。铁和各种氨基酸含量无明显变化（P＜0．05）。肝脏、肺脏、肌肉和翅羽中的锌含量Ⅱ组和Ⅲ组显著增加（P＜0．01）能脏中的锌含量Ⅱ组明显上升（P＜0．05）,Ⅲ组显著提高（P＜0．01）,心脏、脾脏和卵巢无显著影响（P＜0．05）。     

Biochemical effects of di-2-ethylhexyl phthalate.

Di-2-ethylhexyl phthalate (DEHP) is a widely used plasticizer in the plastics industry. Biochemical changes in rat blood and liver were studied at 21 days after 3 intraperitoneal injections of DEHP on days 1, 5 and 10. In the liver, a decrease in the activity of succinic dehyrogenase (SDH) and adenosine triphosphate and an increase in alkaline phosphatase activity was observed. In serum the activity of acid and alkaline phosphatases and glutamic oxaloacetic and glutamic pyruvic transaminases remained unaltered. Under in vitro conditions, only the activity of SDH was inhibited when homogenates or mitochondrial preparations from normal rat liver were incubated with DEHP and the degree of inhibition was related to the concentration of the plasticizer.     

Effect of aflatoxin B1 on CD3 T cells andalkaline phosphatase in the intestine of mice

The aim of the study was to determine the effect of repeated applications of aflatoxin B₁ (AFB₁) on immunocompetent cells (CD3 T cells) and alkaline phosphatase in the intestinal mucosa. Mice were orally treated with AFB₁ for 24 days. The mucosa of the intestine showed a significant decrease in the number of CD3 T cells and a significantly lower level activity of alkaline phosphatase on day 24 in AFB₁ treated mice. Similarly, with changes in the small intestine, qualitative haematological parameters were modified in systemic immunity as lymphopenia, and neutropenia, monocytopenia. AFB₁ treated animals showed reduction in body weight gain and increased liver weight. We supposed that changes found in the small intestine are secondary to primary systemic haematological lesions. The decrease in CD3 T cells suggests a connection with the decrease in the host's resistance to infectious diseases. This revised version was published online in June 2006 with corrections to the Cover Date.     

Experimental cross infections of Fasciola hepatica in lambs and calves.

The effects of experimental infections with Fasciola hepatica of ovine and bovine origin in homologous and heterologous hosts and in uninfected controls were compared; groups comprised 5 animals each. The effects of the infections were monitored by biweekly determinations of packed cell volumes (PCV), serum glutamic oxaloacetic transaminase (SGOT), serum glutamic pyruvic transaminase (SGPT), gamma glutamyl transpeptidase (GGT), serum iron, bilirubin levels, alkaline phosphatase (AlP) and total serum protein levels. Infected animals showed changes in SGOT, SGPT and GGT activity levels, and GGT activity levels, and infected lambs showed changes in PCV and AlP. However, no no significant differences in these serum levels between infected host groups were attributable to fluke strain. At necropsy, calves infected with ovine and bovine strains on an average had about the same number of flukes, but lambs infected with a high dose of the bovine strain on the average had nearly twice the number of flukes as those infected with ovine strain. Weight gains did not differ within host groups; liver damage was extensive in all infected animals. On the basis of these experiments, the pathogenicity of the ovine and the bovine strains of F. hepatica appears to be the same.     

Multivariate analysis of hematological and serum biochemical values in female cynomolgus monkeys (Macaca fascicularis) aged less than a year

Hematological and serum biochemical data obtained from 91 laboratory-bred cynomolgus monkeys (Macaca fascicularis) aged 11 to 362 days were analyzed by the discriminant analysis. All animals used had been bred and reared under uniform environmental conditions at Tsukuba Primate Center for Medical Science, N. I. H., Japan. The examination items were as follows: red blood cell count (RBC), hematocrit value (Ht), hemoglobin concentration (Hb), mean corpuscular volume (MCV), white blood cell count (WBC), glutamic oxaloacetic transaminase activity (GOT), glutamic pyruvic transaminase activity (GPT), total protein concentration (TP), albumin concentration (ALB), albumin-globulin ratio (A/G), blood urea nitrogen (BUN), glucose concentration (GLU), total cholesterol concentration (TCHO), free cholesterol concentration (FCHO), triglyceride concentration (TG), alkaline phosphatase activity (ALP) and calcium concentration (Ca). The animals were divided into four groups (A: Suckling infants, less than 176 days old. B, C, D: Weanlings and juveniles, 121 to 220 days old, 221 to 280 days old, and 281 to 362 days old, respectively). Discrimination was possible among these four groups on the basis of the Mahalanobis' generalized distance. Regarding the canonical discriminant analysis (discriminant analysis with reduction of dimensionality), discrimination was possible. The suckling infant group could be discriminated from the juvenile groups by the first canonical variate. Concerning the juvenile groups, age was highly correlated to the value of the second canonical variate.2+ Judging from an approximate relative eigenvector value for the second canonical variate, the effective discriminant variables were WBC, TP, ALB, A/G, FCHO, TG, and ALP. It can be concluded that these eight parameters are important and useful for monitoring the physiologicals conditions of growing juvenile monkeys.     

An integrated assessment of lead exposure in children: Correlation with biochemical and haematological indices

BackgroundLead (Pb) is a worldwide concern due to its persistent property in the environment. However, due to diminutive evidence and elusiveness, the impact of lead exposure on the biochemical and haematological parameter in school-age children is not well established.AimThis study primarily aimed to investigate blood lead (BL) in children and its association with haematological and biochemical parameter.MethodsA total of 43 children (4–12 years) were recruited in each control and study group. Furthermore, the study group were subdivided into two groups (group A (<10 μg/dl) and group B (>10 μg/dl)). BL level, haematological parameter including haemoglobin, packed cell volume, red blood cells, mean corpuscular haemoglobin, mean corpuscular haemoglobin concentration, total leukocytes count, neutrophils, lymphocytes, monocytes, mean corpuscular volume, red cell distribution width, eosinophil’s, platelets in the whole blood and biochemical parameter such as liver function test (total bilirubin, alkaline phosphatase, serum glutamic-oxaloacetic transaminase, serum glutamic-pyruvic transaminase, total protein, albumin) and kidney function test (sodium, potassium, blood urea nitrogen, creatinine) in serum were measured using anodic stripping voltammeter (ASV), Cell-Dyn Ruby Haematology analyser, Beckman coulter Unicel Dxc 800 Synchron Clinical analyser respectively.ResultsThe arithmetical mean of BL level was 19.93 ± 9.22 μg/dl (median: 17.5 μg/dl; range 9.1–37.4 μg/dl). Only 21 % children had BL levels <10 μg/dl and there were 79 % children with BL levels >10 μg/dl. Blood mean corpuscular haemoglobin concentration, Neutrophils, Monocytes were significantly higher between the control and study group. Additionally, haemoglobin, packed cell volume, red blood cells, mean corpuscular haemoglobin, mean corpuscular haemoglobin concentration, Lymphocytes and mean corpuscular volume intensities were significantly lower in >10 μg/dl group whereas total leukocytes count, neutrophils, monocytes, red cell distribution width, eosinophil’s, platelets levels were statistically higher (p < 0.001).Serum alkaline phosphatase, serum glutamic-oxaloacetic transaminase, total protein, were higher (p < 0.05) and sodium, albumin were significantly lower in the study group. The mean value of sodium, potassium, total bilirubin, alkaline phosphatase, serum glutamic-pyruvic transaminase, total protein and blood urea nitrogen, creatinine in two groups (<10 μg/dl and >10 μg/dl) was not significantly different. Serum glutamic-oxaloacetic transaminase level was significantly higher (p = 0.015) while albumin levels were significantly lower (p = 0.034) in >10 μg/dl group. A statistically significant correlation of BL levels with all haematological parameters was also observed. Creatinine is positively and albumin was negatively correlated with BL levels.ConclusionThe outcomes specify that high BL levels were significantly associated with higher haematological and biochemical indices in exposed children. However, lead like noxious metals severely affected the haematological, kidney and liver health of children.     

Effect of radiation on some haematological parameters and its modification by vitamin E in chicks.

White leghorn male chicks of 1 and 7 day age groups were studied for acute (2.25 Gy) gamma radiation (with or without vit. E pretreatment) induced haematological changes in the peripheral blood at days 1, 3, 5, 7, 14 and 28 postirradiation. A continuous decrease in the erythrocyte numbers was observed in the animals irradiated without vit. E treatment. The changes in haematocrit, haemoglobin, MCV, MCH and MCHC values were in line with the erythrocytic changes reflecting radiation induced damage to the erythroid elements. Animals pretreated with vit. E show lesser depression in the erythrocytic component at all the stages indicating its radio-protective influence. The significant increase in the immature RBC's in the peripheral blood in vit. E treated animals after irradiation, implies enhanced erythropoiesis.     

Repeated dermal toxicity of technical HCH and methyl parathion (50EC) to female rats (Rattus norvigicus).

Repeated dermal application of hexachlorocyclohexane (HCH; 100 mg/kg/day) or methyl parathion (2 mg/kg/day) individually or in combination for 7, 15 and 30 days produced pathomorphological changes in skin, liver, kidney and brain of female rats along with significant enzymatic alterations in the activity of transaminase, alkaline phosphatase lactic dehydrogenase and acetylcholinesterase. The two insecticides in combination though produced severe toxicity on day 30 than at other periods, the changes were not suggestive of any additive or potentiation effect at the test doses.     

Attenuation of the acute adriamycin-induced cardiac and hepatic oxidative toxicity by N-(2-mercaptopropionyl) glycine in rats

The protective effect of the synthetic aminothiol, N-(2-mercaptopropionyl) glycine (MPG) on adriamycin (ADR) induced acute cardiac and hepatic oxidative toxicity was evaluated in rats. ADR toxicity, induced by a single intraperitoneal injection (15 mg/kg), was indicated by an elevation in the level of serum glutamic pyruvic transaminase (GPT), glutamic oxaloacetic transaminase (GOT), creatine kinase isoenzyme (CK-MB), and lactic dehydrogenase (LDH). ADR produced significant elevation in thiobarbituric acid reactive substances (TBARS), indicating lipid peroxidation, and significantly inhibited the activity of superoxide dismutase (SOD) in heart and liver tissues. In contrast, a single injection of ADR did not affect the cardiac or hepatic glutathione (GSH) content and cardiac catalase (CAT) activity but elevated hepatic CAT. Pretreatment with MPG, (2.5 mg/kg) intragastrically, significantly reduced TBARS concentration in both heart and liver and ameliorated the inhibition of cardiac and hepatic SOD activity. In addition, MPG significantly decreased the serum level of GOT, GPT, CK-MB, and LDH of ADR treated rats. These results suggest that MPG exhibited antioxidative potentials that may protect heart and liver against ADR-induced acute oxidative toxicity. This protective effect might be mediated, at least in part, by the high redox potential of sulfhydryl groups that limit the activity of free radicals generated by ADR.     

Discriminant analysis of hematological and serum biochemical values in cynomolgus monkey (Macaca fascicularis) bred and reared under the indoor individually-caged conditions

The data on hematological and serum biochemical properties of laboratory-bred cynomolgus monkeys (Macaca fascicularis) at different ages were analyzed by discriminant analysis. All the animals had been bred and reared under uniform environmental conditions at Tsukuba Primate Center for Medical Science, N.I.H., Japan. The items used were as follows: red blood cell count (RBC), hematocrit value (Ht), hemoglobin concentration (Hb), mean corpuscular volume (MCV), white blood cell count (WBC), glutamic oxaloacetic transaminase activity (GOT), glutamic pyruvic transaminase activity (GPT), total protein concentration (TP), albumin concentration (ALB), albumin-globulin ratio (A/G), blood urea nitrogen (BUN), glucose concentration (GLU), total cholesterol concentration (TCHO), free cholesterol concentration (FCHO), triglyceride concentration (TG) and alkaline phosphatase activity (ALP). In total, 1086 animals in 10 age groups were examined. Data analyses were done with respect to the difference of sex. Discrimination was possible by Mahalanobis' generalized distance between centroids of groups. In canonical discriminant analysis (discriminant analysis with reduction of dimensionality), age was highly correlated to the value of the first canonical variate. From the approximate relative value of the eigenvector of the first canonical variate, the most discriminant variables are WBC, TP, ALB, A/G, TCHO, FCHO, TG, and ALP. It can be concluded that periodic measurement of these 8 parameters is necessary and sufficient to monitor the physiological conditions of growing monkeys.     

Attenuation of the acute adriamycin-induced cardiac and hepatic oxidative toxicity by N-(2-mercaptopropionyl) glycine in rats

The protective effect of the synthetic aminothiol, N-(2-mercaptopropionyl) glycine (MPG) on adriamycin (ADR) induced acute cardiac and hepatic oxidative toxicity was evaluated in rats. ADR toxicity, induced by a single intraperitoneal injection (15 mg/kg), was indicated by an elevation in the level of serum glutamic pyruvic transaminase (GPT), glutamic oxaloacetic transaminase (GOT), creatine kinase isoenzyme (CK-MB), and lactic dehydrogenase (LDH). ADR produced significant elevation in thiobarbituric acid reactive substances (TBARS), indicating lipid peroxidation, and significantly inhibited the activity of superoxide dismutase (SOD) in heart and liver tissues. In contrast, a single injection of ADR did not affect the cardiac or hepatic glutathione (GSH) content and cardiac catalase (CAT) activity but elevated hepatic CAT. Pretreatment with MPG, (2.5 mg/kg) intragastrically, significantly reduced TBARS concentration in both heart and liver and ameliorated the inhibition of cardiac and hepatic SOD activity. In addition, MPG significantly decreased the serum level of GOT, GPT, CK-MB, and LDH of ADR treated rats. These results suggest that MPG exhibited antioxidative potentials that may protect heart and liver against ADR-induced acute oxidative toxicity. This protective effect might be mediated, at least in part, by the high redox potential of sulfhydryl groups that limit the activity of free radicals generated by ADR.