Immunopathological studies of combined effect of copper and aluminium nanoparticles in wistar rats
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Date
2020-10
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G.B. Pant University of Agriculture and Technology, Pantnagar - 263145 (Uttarakhand)
Abstract
The present experiment was conducted to study the effect of copper and aluminium oxide nanoparticles on the immune system of Wistar rats. The experimental study was conducted for period of 90 days. Thirty five wistar rats were randomly allocated into two groups i.e. control and test group containing 20 and 15 rats each, respectively. During the entire course of experiment, control rats were received distilled water and standard feed. While test rats were orally gavaged with Copper oxide nanoparticles (CuONPs) and Aluminium oxide nanoparticles (Al2O3NPs) at half the NOAEL dose i.e. 50mg/kg/day and 3mg/kg/day, respectively along with standard feed and water in the morning time for a period of 90 days. Rats were regularly monitored for any abnormal clinical signs and change in behavior during the experiment. Various hematological, biochemical and immunopathological parameters were studied along with pathomorphological alterations in rats at day 0, 30, 60 and 90 of the experiment. During the entire course of the experiment no aggressive behavior and abnormal clinical signs were showed by the test rats when compared with the control rats. Though reduced body weight was observed in test group rats relative to the control group rats. Study of various hematological parameters showed significant decrease in the hemoglobin, TEC, TLC, ALC and mean lymphocyte count and decrease in PCV, MCH and MCHC in the test rats when compared with the control rats. Biochemical parameters exhibited significant reduction in total serum protein, serum albumin, serum globulin and serum gamma globulin and significant elevation in the level of serum creatinine, serum BUN and liver function enzyme i.e., AST and ALT in test rats. Various immunological parameters were studied during the experiment to investigate the effect of copper and aluminium oxide nanoparticles on body’s immune response. Decreased value of mean HI titre and mean ELISA in test group revealed suppressed humoral immunity in test group. In delayed type hypersensitivity reaction (DTH) decrease in the thickness of the DNFB sensitized skin and in macrophage function test decrease in NBT positive cells was indicative of suppression in cell mediated immunity. During the lymphocyte stimulation test, reduction in Δ OD in splenocytes was observed by using Con-A, PHA-M and LPS mitogens in the test rats. The results denote the lymphocytotoxic effect of copper and aluminium nanoparticles against both mature and immature T and B lymphocytes.
Histopathological lesions were observed in various organs of test rats. Liver showed congestion in central vein, degenerative and necrotic changes in hepatocytes, kupffer cell proliferation and anisonucleation in hepatocytes. Kidneys showed degeneration and necrosis of tubular epithelium, glomerular atrophy, congestion and haemorrhage in glomeruli and interstitium and mononuclear cells infiltration in glomeruli and interstitial spaces. Lung sections demonstrated congestion, emphysema and atelectasis, thickening of interalveolar septa due to infiltration of mononuclear cells. Spleen sections revealed congestion, necrosis and depletion of lymphoid cells at some places. Brain showed neuronal degeneration, perivascular cuffing, satellitosis and gliosis. Heart sections showed congestion in blood vessels and necrosis. Intestinal sections showed lesions of catarrhal enteritis and infiltration of mononuclear cells. Testis sections revealed gap between the seminiferous tubules, focal loss of germinal epithelium, distorted arrangement of spermatogenic cells and degenerative and necrotic changes in seminiferous tubules. Consequently, the present experimental study suggests that nano-copper and nano-aluminium in combination exhibits deleterious effects on immune system of wistar rats when given at the rate of half of the NOAEL dose. The co-exposure of these nanoparicles cause immunosuppression by damaging the immune cells, alter hematological and biochemical attributes along with destructive pathomorphological changes. Based on the above findings, it can be concluded that nanoparticles in combination induce more pronounced immunopathological alterations as well as immunosuppression even in the short period of the experiment.