GAUTAM KAULAHMAD HUSSAIN2023-11-172023-11-172019https://krishikosh.egranth.ac.in/handle/1/5810201427Nanotechnology is a promising tool in every aspect of modern life including agriculture. Nanoproducts like nanofertilizers (nutrients in nanoform) and nanocarriers (nanoporous materials for controlled release) are becoming centre of attraction due to their role in precision agriculture. There is dire need of safety assessment before their application due to environmental exposure and possible health hazard to life forms including humans. Keeping all this in view, the present investigation was designed to assess the safety of ZnO nanofertilizer (ZNF) and mesoporous silica nanocarrier (MSN) taking both in vitro and in vivo model into account. Under in vitro study, cytotoxicity of ZNF and MSN on immune as well as male germ cell was evaluated by MTT, WST8 and neutral red assay. The cell viability in both cases decreased significantly by time (1hr, 4hr) and concentration (1, 5, 10, 25, 50 and 100 μg/ml) dependent treatment of ZNF compared to control. The anti-oxidative enzymes (SOD: Superoxide dismutase, GPX: Glutathione peroxidase) increased significantly (P < 0.01) after 1 hour incubation with 50 μg/ml of ZNF. Lethal Concentration (100 μg/ml) obtained from percentage hemolysis (%hemolysis) assay of RBCs confirms that ZNF is relative toxic than MSN. In neutrophils and male germ cells treated upto 100 μg/ml MSN no significant changes was observed in %viability, %hemolysis as well as in the activities of oxidative stress enzymes as compared to control. Additionally, ZNF at higher concentration leads to significant loss (p<0.05) in viability and membrane integrity of male germ cell as depicted by Eosin-Nigrosin assay and hypo-osmotic swelling test, respectively. In case of in vivo study, lactating nulliparous rats were orally administered 5, 25 and 50mg/kg b.w. ZNF as well as MSN for consecutively 19 days from the first day of parturition. ZNF was distributed significantly to breast milk with increasing dose as quantified by inductively coupled plasma mass spectrometry (ICPMS). Further, ZNF were absorbed by the small intestine and distributed to liver of breast-fed pups. Histopathology study of intestine and liver of offsprings depicted the gross pathological changes caused by milk mediated transfer of ZNF. Most of the ZNF and MSN were excreted through feces of dams. IgA secretion in the intestinal fluid of offsprings increased significantly on increasing dose of ZNF to dams. Liver injury marker enzymes (AST, ALT) increased significantly in dams and offspring postnatally. The level of cytokines (TNF-α, IL-1β) in serum increased significantly in the offsprings of 25mg/kg and 50mg/kg bw group. The total cytochrome P450 reductase and total antioxidant capacity decreased significantly in the offsprings of 50mg/kg ZNF given dams group. Further, nitric oxide production and phagocytosis activity of macrophages from offsprings of 50mg/kg ZNF dams group decreased significantly (p<0.05). Real-time polymerase chain reaction indicated milk mediated expression of anti-oxidative enzymes (SOD, GPX), apoptosis (BAX) and cytokines (TNFα, IL1β) genes in offspring neutrophils after oral administration of 50/mg kg b.w ZNF to dams. These results provide information that MSN is comparatively safer than ZNF upto 100 μg/ml concentrations in vitro and 50mg/kg body weight in vivo intubation to dams after parturition.EnglishThesis