Preeti BagriVipin2024-08-082024-08-082023-07https://krishikosh.egranth.ac.in/handle/1/5810213023The human population is increasing day by day, which leads to increase in food demand and use of pesticides. The imidacloprid (IMI) is a neonicotinoid, which act as agonist on nicotinic acetylcholine receptors (nAchRs), specifically at the α-subunits of the nicotinic receptor and use of imidacloprid is increasing. Quercetin (Que) is a bioflavonoid, mainly found in onions, grapes and apple. Quercetin is well known for its pharmacological properties like antioxidant, anti-cancerous, neuroprotective, anti-inflammatory etc. The pharmacological application of quercetin is limited due to its low oral bioavailability (less than 17% in rats and even 1% in humans), low brain permeability and its hydrophobic nature, short biological half-life. However, nanoparticles of quercetin have attracted particular attention in therapeutics due to their excellent stability, high bioavailability and ready ability of crossing the blood brain barrier (BBB). In present study, quercetin nanoparticles were synthesized and characterization was done by hydrodynamic diameter, UV-visible spectra, FT-IR, Zeta potential, SEM, TEM and encapsulation efficiency analysis. In vitro analysis of biocompatibity of nanoparticles was done by hemolytic assay. For in vivo subacute toxicity study for 28 days, total 48 mice were taken and divided in eight groups with six animals in each group. Group 1, 2, 3 and 4 received 3% gum acacia, 22 mg/kg b.wt. imidacloprid, 25 mg/kg b.wt. quercetin and 25 mg/kg b.wt. quercetin nanoparticles high dose [QNPs (HD)], respectively. Group 5, 6, 7 and 8 received 22 mg/kg b.wt. imidacloprid + 25 mg/kg b.wt. quercetin, 22 mg/kg b.wt. imidaclopid + 25 mg/kg b.wt. QNPs (HD), 22 mg/kg b.wt. imidacloprid + 12.5 mg/kg b.wt. quercetin nanoparticle medium dose [QNPs (MD)] and 22 mg/kg b.wt. imidacloprid + 6.25 mg/kg b.wt. quercetin nanoparticles low dose [QNPs (LD)], respectively. Test for Anti-inflammatory effect (Carrageenan induced paw edema), neurobehavioural effect (SMA, Forced locomotor activity and Heat induced algesia), Mutagenic effects (MNT, Comet assay and SHA), oxidative stress in brain and liver (TP, LPO, SA and GSH), acetylcholinesterase activity in brain and histopathology of bone marrow, cerebrum, cerebellum and testes were performed. Imidacloprid predisposed animal to inflammation and both quercetin and quercetin nanoparticles decreased this inflammation. In MNT, there was significant increase in MnPCE, MnNCE and decrease P/N ratio in imidacloprid group as compared to control whereas both quercetin and quercetin nanoparticles decreased occurrence of micronuclei and increase P/N ratio. In comet assay a significant increase in comet length, tail length, tail DNA and tail moment was noticed in imidacloprid group as compared to control whereas both quercetin and quercetin nanoparticle decreased these parameters when given in combination with imidacloprid. In SHA, there was significant increase in abnormal sperm in imidacloprid group as compared to control whereas highest reduction in sperm head abnormality in imidacloprid + quercetin nanoparticles high dose was noticed. Both quercetin and quercetin nanoparticles protect brain and liver tissue from imidacloprid induced oxidative stress. There was no significant change in acetylcholinesterase activity in any group compared to control. In histopathological findings, imidacloprid produced degenerative changes in bone marrow, cerebrum, cerebellum and testes. Both quercetin and quercetin nanoparticles showed ameliorative effect markedly by causing restoration of degenerative changes produced by imidacloprid. On the basis of above results, it may be concluded that both quercetin and quercetin nanoparticles have ameliorative effect against imidacloprid induced subacute toxicity.EnglishThesis