Histopathological changes induced by quinalphos in the testes and liver of Indian dessert gerbils, Meriones hurrianae (Jerdon)

Single intraperitoneal injection of quinalphos (15 mg/kg body weight) produced several pathological changes in the testes and liver of the Indian desert gerbil, Meriones hurriane (Jerdon). The degenerative changes included testicular atrophy, reduction in tubular size and enlarged interstitium. In the spermatogenic cells, necrosis and karyopycnosis were observed. Hepatic cells revealed cytoplasmolysis, vacuolation and necrosis. The nuclei of the hepatocytes showed karyorrhexis and karyolysis.     

Histopathological and biochemical changes in guinea pigs after repeated dermal exposure to benzene hexachloride.

Dermal application of benzene hexachloride in daily doses of 100, 200 and 500 mg/kg for a total period of 30 days caused significant changes in male guinea pigs. The animals exposed to high doses of benzene hexachloride (1,2,3,4,5,6-hexachlorocyclohexane) (BHC) (BHC) died within 5--12 days. There was no mortality in 100 mg/kg/day but significant pathologic and biochemical changes were observed in the vital organs of the experimental animals. Massive congestion and thickened blood vessels were seen in liver of the BHC treated animals in comparison to the normal picture of the controls. Similarly, testicular changes included mild to severe pathologic lesions. There was no change in the epididymis, kidney, spleen, brain and lungs. The changes in the skin were mild and no signs of dermatitis were observed in the BHC painted areas. The activity of glutamic oxaloacetic transaminase (GOT), glutamic pyruvic transaminase (GPT) and alkaline phosphatase in liver and serum revealed significant changes from that of the controls. The significance of biochemical changes with the tissue damage of the insecticide exposed animals are discussed.     

Pulmonary biochemical and histological alterations after repeated low-level blast overpressure exposures.

Blast overpressure (BOP), also known as high energy impulse noise, is a damaging outcome of explosive detonations and firing of weapons. Exposure to BOP shock waves alone results in injury predominantly to the hollow organ systems such as auditory, respiratory, and gastrointestinal systems. In recent years, the hazards of BOP that once were confined to military and professional settings have become a global societal problem as terrorist bombings and armed conflicts involving both military and civilian populations increased significantly. We have previously investigated the effects of single BOP exposures at different peak pressures. In this study, we examined the effects of repeated exposure to a low-level BOP and whether the number of exposures or time after exposure would alter the injury outcome. We exposed deeply anesthetized rats to simulated BOP at 62 +/- 2 kPa peak pressure. The lungs were examined immediately after one exposure (1 + 0), or 1 h after one (1 + 1), two (2 + 1), or three (3 + 1) consecutive exposures at 3-min interval. In one group of animals, we examined the effects of repeated exposure on lung weight, methemoglobin, transferrin, antioxidants, and lipid peroxidation. In a second group, the lungs were fixed inflated at 25 cm water, sectioned, and examined histologically after one to three repeated exposures, or after one exposure at 1, 6, and 24 h. We found that single BOP exposure causes notable changes after 1 h, and that repeating BOP exposure did not add markedly to the effect of the first one. However, the effects increased significantly with time from 1 to 24 h. These observations have biological and occupational implications, and emphasize the need for protection from low-level BOP, and for prompt treatment within the first hour following BOP exposure.     

Histopathological changes in the reproductive system (ovaries and testes) of Oreochromis mossambicus following exposure to DDT

This study assesses the effects of 1,1-bis (4-chlorophenyl)-2,2,2-trichloroethane (DDT) on the reproduction and gonadal histology of adult Mozambique tipalia (Oreochromis mossambicus). The fish were allowed to breed, following exposure to 2 and 5μg/l of waterborne technical-grade DDT for 40 days. Fertilized eggs were artificially incubated. In the 5μg/l exposure, posthatch survival was significantly lower, and prevalence of larval skeletal deformities significantly higher, compared to the control (p<0.05). Incomplete axial development was the common gross deformity in posthatch larvae, caused by failure to develop chondroblasts posterior to the buccopharyngeal cavity. There were no significant differences in the gonadosomatic index of exposed and non-exposed male and female adults. The exposure caused increased oocyte atresia in the ovaries and disorganization of seminiferous lobules in the testes of adults. DDT exposure reduced survival and increased deformities in larvae, at levels that did not cause severe histopathological changes to parental gonads.     

Effects of single and repeated exposures to thermo-oxidative degradation products of poly(acrylonitrile-butadiene-styrene) (ABS) on rat lung,liver, kidney,and brain

Male Wistar rats were exposed to thermo-oxidative degradation products of heated poly(acrylonitrile-butadiene-styrene) (ABS). The exposures were conducted once, three times or ten times (5 nights/week, 6 h/night) in the nighttime. The degradation products included styrene, various nitriles, aldehydes, acids, and a significant aerosol fraction. The oxygen concentration in the exposure chamber was constantly above 20%. The shortest exposures caused a significant reduction of the 0-deethylation activity in lung and kidney but not in liver, as well as a decrease in tissue reduced glutathione concentration in liver and kidney but not in lung. These effects well-nigh disappeared during the two-week exposure. In these rats the cerebral glutathione was below the control range. Superoxide dismutase activity increased in liver and brain during the three-day exposure. In liver the activity reached the control value after the two-week exposure but the cerebral activity was significantly lower than in controls. The complex mixture of noxious compounds in the ABS fumes does not readily allow identification of causative agents. Nitrile-dependent histotoxic, peroxidative and reactive metabolite mediated mechanisms may be involved.     

Effect of para-chlorophenylalanine on male rats: histopathological and biochemical changes in the testes

Spermatogenically active testes of rat challenged by 100 mg/kg body weight of p- Chlorophenylalanine for 45 days displayed marked and drastic changes in the seminiferous epithelium. Degenerative changes followed by immense necrosis of germ cells lead to complete breakdown of seminiferous tubules. Leydig cells, however, remained unaffected histologically in the treated animals. Among the accessory sex organs, epididymis alone showed a marked decrease in its weight. A biochemical study in the drug treated rats revealed a significant accumulation of glycogen in the testes accompanied by increase in the activities of enzymes like the succinic dehydrogenase, glucose-6-phosphatase, ATP-ase and acid phosphatases. However, a marked decrease was noticed in the activities of enzymes like alkaline phosphatase, phosphohexose isomerase and lactate dehydrogenase. No significant change was found in the protein, DNA and RNA concentrations in the drug treated testes. The histological and biochemical changes induced in the testes by p-CPA suggest the deleterious effect of the drug on the seminiferous tubules of the testes.     

Histopathological changes in gill and liver of Capoeta capoeta living in the Karasu River,Erzurum

The contamination of surface waters by different pollutants is an important problem worldwide. In this study, the histopathological effects of water pollution were investigated on freshwater fish species Capoeta capoeta caught from the Karasu River. Fish were caught at three different sites in the Karasu River, namely, A?kale, Dumlu, and Serçeme. The histological changes in gill and liver of fish were detected microscopically and evaluated with quantitative analyses. In addition, heavy metals have also been determined in surface water samples from these sites. Results showed that the A?kale site was polluted by different kinds of heavy metals. In A?kale site, some heavy metals such as Cd, Al, As, Pb, and Mn levels were mostly detected at concentrations above than the accepted values by the Turkish Standards Institute. The presence of gill and liver histological alterations were assessed by the degree of tissue change (DTC). In gill filaments, hypertrophy and hyperplasia of the gill epithelium, lamellar epithelial lifting, lamellae shortening, vasodilatation, lamellar disorganization, blood congestion, fusion, and aneurysm were observed. In the liver, the changes included an increase in the number and size of melanomacrophage aggregates, nonhomogenous parenchyma, proliferation of the hepatopancreas, sinusoidal dilatation, vacuolization, hypertrophy of the hepatocytes, congestion and degeneration of central vein, blood congestion, pyknotic nucleus, focal necrosis, and hepatic granuloma. The histological lesions were comparatively most severe in liver. The DTC means were varied from slight to moderate of gill and moderate to severe of liver tissue in the A?kale site, thus the site is considered to be of low quality. Some pathological alterations were observed in the Serçeme site, although their distribution was lower than sites Dumlu and especially A?kale. The least DTC means of the Serçeme site demonstrated their good environmental quality. The results suggest that there is a close relationship between amounts of pathological alterations and environmental contamination. © 2014 Wiley Periodicals, Inc. Environ Toxicol 30: 904–917, 2015.     

Histopathological lesions,P-glycoprotein and PCNA expression in zebrafish (Danio rerio) liver after a single exposure to diethylnitrosamine

The presence of carcinogenic compounds in the aquatic environment is a recognized problem. ABC transporters are well known players in the multidrug-resistance (MDR) phenomenon in mammals associated with resistance to chemotherapy, however little is known in fish species. Thus, the aim of this study was to induce hepatic tumours and evaluate long-term effects on P-glycoprotein (P-gp) and proliferating cell nuclear antigen (PCNA) proteins in Danio rerio liver, after exposure to diethylnitrosamine (DEN). Several hepatic histopathological alterations were observed in zebrafish after exposure to DEN including pre-neoplastic lesions 6 and 9 months post-exposure. After 3, 6 and 9 months of exposure to DEN, P-gp and PCNA proteins expression were up-regulated. In conclusion, this study has shown that zebrafish ABC transporters can play a similar role as in human disease, hence zebrafish can be used also as a biological model to investigate in more deep mechanisms involved in disease processes.     

Methylmercury exposure for 14 days (short-term) produces behavioral and biochemical changes in mouse cerebellum,liver, and serum

ABSTRACT

Various studies on methylmercury (MeHg)-induced toxicity focused on the central nervous system (CNS) as a primary target. However, MeHg-mediated toxicity is related to metallic interaction with electrophilic groups, which are not solely restricted to the CNS, but these reactive groups are present ubiquitously in several systems/organs. The aim of this study was thus to examine MeHg-induced systemic toxicity in mice using a standardized neurotoxicology testing exposure model to measure cerebellar neurotoxicity by determining biochemical and behavioral parameters in the cerebellum. After 2 weeks exposure to MeHg (40 µg/ml; diluted in drinking water; ad libitum), adult male Swiss mice showed a marked motor impairment characteristic of cerebellar toxicity as noted in the following tests: rotarod, beam walking, pole, and hind limb clasping. MeHg treatment resulted in Hg deposition in the cerebellum as well as reduction in cerebellar weight, glutathione peroxidase (GPx) activity, and interleukin (IL)-6 levels. MeHg ingestion increased cerebellar glutathione reductase (GR) activity and brain-derived neurotrophic factor (BDNF) levels. In addition to cerebellar toxicity, MeHg treatment also elevated total and non-high density lipoprotein (non-HDL) cholesterol levels, as well as serum aspartate transaminase (AST) and alanine transaminase (ALT) enzymatic activities, systemic parameters. Increased liver weight and reduced serum urea levels were also noted in MeHg-exposed mice. Taken together, our findings demonstrated that a well-standardized exposure protocol to examine MeHg-induced neurotoxicity also produced systemic toxicity in mice, which was characterized by changes in markers of hepatic function as well as serum lipid homeostasis.     

Morphological and biochemical changes in the liver of various species in experimental phospholipidosis after diethylaminoethoxyhexestrol treatment.

The mechanism of druginduced experimental phospholipidosis was studied in several species by the administration of diethylaminoethoxyhexestrol. Rabbits, rats, mice, dogs, and guinea pigs developed microscopic and biochemical abnormalities, while hamsters were less affected. In the liver of affected species characteristic subcellular changes were found, accompanied by phospholipid accumulation. Hepatic lesions consisted of concentric lamellar bodies with varying degrees of osmic affinity, representing secondary lysosomes characterized by cytochemical methods. Accumulation of these bodies was also seen in Kupffer, endothelial, and biliary epithelial cells. The intensity of the changes was related to species susceptibility. Biochemical studies revealed an overall increase of total phospholipids in the affected species, together with changes in the relative distribution of individual phospholipids and the appearance of unidentified components. The activity of microsomal drug metabolizing enzymes and microsomal phospholipid synthesis were diminished. The lesions closely resembled those observed in man after treatment with diethylaminoethoxyhexestrol and are related to altered phospholipid metabolism with subsequent changes in microsomal drug metabolizing enzyme activity.     

Brain benzodiazepine receptors and their rapid changes after seizures in the Mongolian gerbil

To elucidate the physiological role of benzodiazepine receptors in convulsion, these receptors were studied in the brain of the Mongolian gerbil (Meriones unguiculatus), an animal model used for the study of epilepsy. Benzodiazepine binding sites in the gerbil brain were demonstrated using [3H]diazepam. The binding was saturable and stereospecific. Benzodiazepines inhibited [3H]diazepam binding to the membranes and their ability to inhibit the binding closely correlated with their potency as anticonvulsants. These results showed that the characteristics of the benzodiazepine receptors in the Mongolian gerbil were similar to those obtained from rat and human brain. Seizures increase the specific binding of [3H]diazepam to the membranes of all regions of the gerbil brain, the most remarkable increase seen in the striatum. Time course studies showed that the increase reached a maximum 10 min after the seizure and the binding returned to the control level within 20 min. The increase in specific [3H]diazepam binding was due almost entirely to shifts in the affinity of [3H]diazepam for its receptors. Thus, the seizures may not be due to changes in the benzodiazepine receptors, and seizures produce an increase in receptor binding, which may be related to a physiological modification of excessive excitation.     

Histopathological changes in rat pancreas after fasting and cassava feeding.

Histopathological changes in rat pancreas were induced by cyclic periods of experimental malnutrition or by cassava (manioc) feeding for 11 weeks. Decline of body weight was correlated with decrease in testicular fat pad weight as a measure of body fat stores. A marked decrease in pancreatic weight in the cassava-fed group was correlated with shrinkage of acinar structures and degenerative features in exocrine pancreas. In the malnutrition group vacuolisation and loss of tissue architecture were observed in some parts of the organ. No signs of ductal obstruction as a tentative cause of pancreatic pathology after malnutrition could be detected. Loss of islets tissue was occasionally seen in degenerative areas. It is concluded that histopathological changes in exocrine pancreas result from malnutrition and cassava feeding differentially and precede ultimate degenerative processes of pancreas endocrine tissue. Tropical malnutrition type diabetes and low protein related diabetes may in their etiology be different entities, but may coincide in practice and aggravate each other to yield severe and irreversible morbidity.     

Airway inflammation and adjuvant effect after repeated airborne exposures to di-(2-ethylhexyl)phthalate and ovalbumin in BALB/c mice

BACKGROUND: Epidemiological studies have suggested an association between exposure to phthalate plasticizers, including di-(2-ethylhexyl)phthalate (DEHP), and increased prevalence of asthma, rhinitis or wheezing. Furthermore, studies in mice have demonstrated an adjuvant effect from DEHP after parenteral administration with the model allergen ovalbumin (OVA). OBJECTIVE: Exposures to DEHP were investigated for adjuvant effects and airway inflammation in a mouse inhalation model. METHODS: BALB/cJ mice were exposed to aerosols of 0.022-13 mg/m(3) DEHP and 0.14 mg/m(3) OVA 5 days/week for 2 weeks and thereafter weekly for 12 weeks. Mice exposed to OVA alone or OVA+Al(OH)(3) served as control groups. Finally, all groups were exposed to a nebulized 1% OVA solution on three consecutive days. Serum, bronchoalveolar lavage (BAL) fluid, and draining lymph nodes were collected 24h later. RESULTS: In the OVA+Al(OH)(3) group, significantly increased levels of OVA-specific IgE and IgG1 in serum as well as of eosinophils in BAL fluid were observed. DEHP affected OVA-specific IgG1 production in a concentration-dependent manner, whereas little effect was seen on IgE and IgG2a. Dose-dependent increases in inflammatory cells were observed in BAL fluids, leading to significantly higher lymphocyte, neutrophil and eosinophil numbers in the OVA+13 mg/m(3) DEHP group. Ex vivo cytokine secretion by cultures of draining lymph nodes suggested that DEHP has a mixed Th1/Th2 cytokine profile. CONCLUSION: Airborne DEHP is able to increase serum IgG1 and lung inflammatory cell levels, but only at very high concentrations. Realistic DEHP levels do not have an adjuvant effect or induce allergic lung inflammation in the present mouse model.     

Histopathological and biochemical changes in lung tissues of rats following administration of fluoride over several generations

The possible effects of multigenerational administration of sodium fluoride (NaF) via drinking water on lung tissue morphology and biochemistry and body and lung weight were investigated in second-generation adult male rats. For this purpose we selected 45 Albino adult Wistar rats in nine cages, each of which consisted of four females and one male. Twenty-eight pregnant rats were selected for the experiment, divided into four groups of seven rats given 1 (control group), 10, 50 and 100 mg l(-1) NaF in drinking water during the gestation period. After gestation the rats had 165 pups in total. The mothers received fluoridated water during the lactation period and the offspring of the first generation had access to fluoridated water during the suckling period (21 days) and after the weaning period (30 days) until they became mature and at the start of the second part of the experiment. During this time 23 pups died and 79 female and 63 male first-generation rats survived. These first-generation rats were then used to obtain the second-generation offspring in the same manner as before, which were subjected to the same treatments. At the end of 6 months the rats were sacrificed and autopsied. Serum fluoride levels and the activities of principal antioxidant enzymes were determined in lung tissue samples taken from all groups. In addition, the lung tissues were submitted for histopathological examination. Histological findings showed alveolar congestion, alveolar cell hyperplasia and necrosis, prominent alveolar septal vessels, epithelial desquamation and macrophages in the alveolar spaces in the experimental groups. Additionally, there were inflammatory infiltrations in peribronchial, perivascular, intraparenchymal and respiratory tract lumen; intraparenchymal hyperaemic vessels; respiratory epithelial desquamation and proliferation; intraparenchymal thick walled vessels; parenchymal fibrosis; bronchiolitis; pneumonic and focal emphysematous areas. Furthermore, the lung parenchyma was observed to have a distorted appearance with loss of alveolar architecture. These histopathological findings were more pronounced for the rat groups of 50 and 100 mg l(-1) fluoride. No significant histopathological changes were observed in the rats of the control group. The increased activities of superoxide dismutase (SOD) and reduced glutathione peroxidase (GSH-Px) and the decreased activity of catalase (CAT) in the lung tissues with 10 mg l(-1) fluoride might indicate activation of the antioxidant defence mechanism. The decrease in SOD, GSH-Px and CAT activities with 50 and 100 mg l(-1) fluoride and the increase in thiobarbituric acid-reactive substance levels might be related to oxidative damage that occurred in the lung. This multigenerational evaluation of the long-term effect of different doses of fluoride intake through drinking water on lung damage shows that the lung tissues were damaged, there was emphysema and inflammation of lung parenchyma associated with loss of alveolar architecture and the degree of lung damage seemed to correlate with the increased dosage of fluoride. A similar relationship was observed between the degree of lung damage, body and lung weight and serum fluoride levels according to the fluoride dose. Therefore, these results contribute to a better understanding of chronic fluoride toxicity in lung tissue of second-generation rats, especially via drinking water, and the biochemical findings were in agreement with histological observations. In addition, increased fluoride concentration did not affect reproduction or the number of pups dying but the body weight and lung weight ratios were affected by the high dose of fluoride in a dose-related pattern.     

Carbendazim-induced haematological, biochemical and histopathological changes to the liver and kidney of male rats

Carbendazim is a systemic broad-spectrum fungicide controlling a wide range of pathogens. It is also used as a preservative in paint, textile, papermaking and leather industry, as well as a preservative of fruits. In the present study, carbendazim was administered at 0, 150, 300 and 600 mg/kg per day doses orally to male rats (Rattus rattus) for 15 weeks. At the end of the experiment, blood samples, liver and kidney tissues of each animal were taken. Serum enzyme activities, and haematological and biochemical parameters were analysed. In toxicological tests, 600 mg/kg per day doses of carbendazim caused an increase of albumin, glucose, creatinine and cholesterol levels. Also, at the same doses, white blood cell and lymphocyte counts decreased. However, mean cell hemoglobin and mean cell hemoglobin concentrations increased. Histopathological examinations revealed congestion, an enlargement of the sinusoids, an increase in the number of Kupffer cells, mononuclear cell infiltration and hydropic degeneration in the liver. At the highest doses, congestion, mononuclear cell infiltration, tubular degeneration and fibrosis were observed in the kidney tissue. These results indicate that 300 and 600 mg/kg per day carbendazim affected the liver and kidney tissue and caused some changes on haematological and biochemical parameters of rats.     

Histopathological and biochemical alterations induced by intramuscular injection of Bothrops asper (terciopelo) venom in mice

The local and systemic pathological changes induced by an i.m. injection of 100 micrograms of Bothrops asper venom in mice were studied histologically and by following the changes in serum levels of enzymes, proteins, ATP and lactate, as well as alterations in hematocrit and clotting time. B. asper venom induced a rapid and marked increase in serum levels of creatine kinase, aspartate aminotransferase and lactate dehydrogenase, but not alanine aminotransferase or alkaline phosphatase. A local myonecrosis and hemorrhage was observed, with the lungs collapsing by 24 hr and the kidneys showing glomerular congestion and vacuolar degeneration of tubular cells. Only minor histopathological changes were observed in cardiac muscle and liver. Both ATP and lactate blood levels decreased after venom injection, whereas there were no changes in serum protein concentration. Blood incoagulability was observed 1 and 3 hr after envenomation. Antivenom neutralized venom-induced increases in serum enzyme levels following preincubation with venom, indicating that antivenom contains antibodies against tissue-damaging toxins. However, when antivenom was administered i.v. at different time intervals after venom injection, neutralization was only partial, with the exception of defibrinating activity, which was totally neutralized even after a delay of 1 hr in administering antivenom.     

Immunologic responses of cynomolgus monkeys after repeated inhalation exposures to enzymes and enzyme--detergent mixtures

Sera from monkeys repeatedly exposed by inhalation to bacterial enzymes, to a detergent, or to various enzyme-detergent mixtures were examined for the presence of enzyme-specific IgE and precipitating antibodies. In addition, lung sections were examined by immunofluorescence for deposits of immunoglobulins, complement, and fibrinogen. No clear-cut evidence was obtained for the presence of enzyme-specific IgE. However, precipitating antibodies were found in each group of monkeys exposed to either the enzyme alone or to the various enzyme-detergent mixtures. The precipitin responses were found to be dependent upon the dose of enzyme employed for inhalation exposure and to be potentiated by the presence of detergent in the inhalation mixtures. Results of immunofluorescent studies suggested that the presence of precipitating antibodies in the sera of the monkeys was not correlated with pulmonary pathological changes.