Immunopathology of copper nanoparticles in Winstar rats
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Date
2019-08
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G.B. Pant University of Agriculture and Technology, Pantnagar - 263145 (Uttarakhand)
Abstract
The present study was carried out for a period of 90 days to study the immunopathology of copper nanoparticles in Wistar rats. For this study, a total of 35 rats of both the sexes were randomly divided into two groups viz. group 1 and group 2. Group 1 was kept as control and consisting of 20 rats. Group 2 was nanocopper treated and comprising of 15 rats. The rats in group 1 were provided with standard diet and water while
the rats in group 2 along with standard recommended feed and RO water, were additionally given copper nanoparticles mixed in distilled water orally at NOAEL dose rate of 100 mg/kg body weight/day from 0 day of experiment till 90th day post treatment. Immunopathological, gross and histopathological studies were carried out at 0, 30th, 60th and 90th DPT. Transmission Electron Microscopy of liver, kidney and spleen was done at 90th DPT. No apparent behavioural and clinical signs were recorded in rats of control and treated groups over a period of 90 days. Mean body weight showed increase in nano-copper treated group as compared to control group. Haematological parameters showed decrease in the mean haemoglobin, mean packed cell volume, mean total leucocyte count, mean absolute lymphocyte count and mean lymphocyte count in nano-copper treated group as compared to control group. There was an increase observed in absolute neutrophil count and mean neutrophil count. Mean thickness of the skin of rat measured in delayed type hypersensitivity reaction through DNFB and mean NBT positive cells in macrophage function test were found to be decreased in nano-copper treated group as compared to control group. Biochemical parameters like total serum protein, serum albumin, serum globulin and serum gamma globulin showed decrease in values in nano-copper treated group as compared to control group. Mean HI titre and mean ELISA values of experimental rats were found to be decreased in nano-copper treated group as compared to control group. There was an elevated level of serum creatinine and liver function enzyme i.e., Aspartate aminotransferase in nano-copper treated group as compared to that of control group. The mean values of delta optical density of experimental rats in lymphocyte stimulation test using Con-A, PHA-M and LPS were found to be increased in nano-copper treated group as compared to control group. In treated group, liver showed cyst and nodule formation on gross examination. However, no observable gross lesions were noticed in other organs of treated group and in control group. Histopathological lesions were observed in various organs. Liver showed congestion in central vein, degenerative and necrotic changes in hepatocytes, sinusoidal dilatation and infiltration of mononuclear cells in intercellular spaces and around central vein. Kidneys of treated group showed degeneration and necrosis of tubular epithelium, glomerular shrinkage, congestion and haemorrhage in glomeruli, congestion in blood vessels, haemorrhage in interstitium and mononuclear cells infiltration in glomeruli and interstitial spaces. Microscopically, the lung sections of treated group demonstrated congestion, emphysema and atelectasis at places, thickening of interalveolar septa and infiltration of mononuclear cells at many places in lung parenchyma. Brain showed
perivascular cuffing, necrosis, vacuolations in brain parenchyma and congestion in blood vessels. Spleen sections of treated group microscopically revealed congestion, necrosis and depletion of lymphoid cells at some places. Intestinal sections of treated group microscopically showed lesions of catarrhal enteritis and infiltration of mononuclear cells. Testis sections of treated group microscopically revealed gap between the seminiferous tubules and degenerative and necrotic changes in spermatids. Heart sections of treated group microscopically showed congestion in blood vessels and necrosis. Microscopically, thymus sections of treated group revealed congestion and lymphoid cell depletion at places. However, no microscopic lesions were observed in tissue sections of control group. Transmission electron microscopy of lung, kidney and spleen revealed electron dense areas of copper nanoparticles as aggregates, agglomerates and individual small size forms. The present study can be concluded that the nano-copper in NOAEL dose is exerting its deleterious effects on vital organs/tissues/systems of the body that may lead to immunopathology, hepatopathy, nephropathy, neuropathy and may adversely affect the reproductive health of animals. Further studies should be carried out in different animal models using varied doses and increased duration of copper nanoparticles to exactly find out the immunopathological alterations. Moreover, future research plans should be done regarding
the interaction of copper nanoparticles with DNA as some studies suggested that they can cause DNA damage and cytotoxicity in various cell lines. Also, future studies should be carried out regarding comparative effects of copper nanoparticles in male and female rats so as to assess its pathological effects on reproductive organs besides, sterility, genotoxicity and teratogenic effects.
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