Microarchitecture of midbrain section (×10) in rats 4 weeks post-exposure to different concentrations of ZALH (A), ZALL (B), ZAH (C), ZAL (D) and vehicle control (E). Substantia

nigra (SN), with abundant of dopaminergic neurons well outline from the brain of the control rats (E). The brain of all the four treated groups of animals also displayed similar features after H & E stain and viewed at ×10 magnification. No changes were seen in the treated group that could be attributed to the effect of nanocomposite exposure. Some inflammatory changes were noticed in Cilengitide ic50 kidney sections of ZALH and ZAH groups compared to VC group (Figures 7A, 4B, and 8). Notably, there were some leukocyte infiltrations in both cases. These changes are dose dependent, seen only in the two high-dose-treated rats but not the lower-dose-exposed animals. Drug-induced renal toxicity in the form of inflammation is a common finding [28], some of which are dose related. They can affect the glomerulus, renal tubular cells and/or the surrounding renal interstitium. This finding is also in agreement with the pathological observation in the case of orally administrated zinc oxide nanoparticle to mice [29],

where both oral and intra-peritoneal administration of the nanoparticle at different doses demonstrated inflammatory changes in the liver, kidney and lungs [29]. Figure 7 Microscopic appearance of the kidney stained with H & E. Microarchitecture of kidney tissues stained with H & E and viewed at ×10 magnification in rats 4 weeks post-exposure to different concentrations of KPT-8602 ZALH (A), ZALL (B), ZAH (C), ZAL (D) and vehicle control (E). G, glomerular; T, tubule. Micrographs (A) and (C) (encircled areas) show some leukocyte infiltrations which are eosinophilic

glomerular due to inflammation likely caused by high dose of the nanocomposite delivery system. The two areas from (A) and (C) were viewed under higher magnification and they are presented in Figure 7. Figure 8 Microscopic appearance of the kidney stained with H & E. Histopathology of the kidneys tissue at ×40 magnification in rats 4 weeks post-exposure to different concentrations of ZALH (Ai) and ZAH (Ci). The tissue sections were stained with H Acetophenone & E. Micrographs from the two groups treated with 500 mg/kg of ZAL and ZA, respectively, showing leucocyte infiltration (L) of the glomeruli due to inflammation. Transition electron microscopy The TEM analysis of the neuronal cells from substantia nigra demonstrated an intact neuron with well-defined nucleus that has a well-delineated peripheral nuclear condensation, which is densely opaque (Figure 9). The shapes were found to be round to ovoid with abundant other cellular organelles notably the mitochondria find more maintaining its cristae and opaque membrane.