ABSTRACT
6-Thioguanine encapsulated chitosan nanoparticles (6-TG-CNPs) has formulated by the ionic-gelation method. Morphologically, the 6-TG-CNPs were spherical and showed mean size, PDI, zeta potential, and entrapment efficiency of 261.63 ± 6.01 nm, 0.34 ± 0.10, +15.97 ± 0.46 mV and 44.27%, respectively. The IR spectra confirmed the 6-TG complex with chitosan. The in vitro drug release profile of 6-TG-CNPs revealed an increase in sustained-release (91.40 ± 1.08% at 48 h) at pH 4.8 compared to less sustained-release (73.96 ± 1.12% at 48 h) at pH 7.4. The MTT assay was conducted on MCF-7 and PA-1 cell lines at 48 h incubation to determine % cell viability. The IC50 values of 6-TG, 6-TG-CNPs, and curcumin for MCF-7 were 23.09, 17.82, and 15.73 µM, respectively. Likewise, IC50 values of 6-TG, 6-TG-CNPs, and curcumin for PA-1 were 5.81, 3.92, and 12.89 µM, respectively. A combination of 6-TG-CNPs (IC25) with curcumin (IC25) on PA-1 and MCF-7 showed % cell viability of 43.67 ± 0.02 and 49.77 ± 0.05, respectively. The in vitro cytotoxicity potential in terms of % cell viability, early apoptosis, G2/M phase arrest, and DNA demethylating activity of 6-TG-CNPs alone and combination with curcumin proved to be more effective than that of 6-TG on PA-1 cells.
Subject(s)
Antineoplastic Agents/pharmacology , Chitosan/chemistry , Curcumin/chemistry , Nanoparticles/chemistry , Thioguanine/pharmacology , Antineoplastic Agents/chemistry , Apoptosis/drug effects , Cell Cycle Checkpoints/drug effects , Cell Line, Tumor , Cell Survival/drug effects , Drug Carriers/chemistry , Drug Liberation , Humans , MCF-7 Cells , Particle Size , Thioguanine/chemistryABSTRACT
The present study was undertaken to assess the testicular toxicity following short-term exposure to cypermethrin (α-CP) in albino mice. Cypermethrin was dissolved in arachis oil and administered to two groups of mice (n = 12/group) orally at the dose rate of 250 mg/kg body weight, once a day for 28 days. Fifty percent of the animals in both the groups were sacrificed on day 14 and the remaining on day 28. Plasma samples were subjected to radioimmunoassay to determine testosterone levels. The testes were collected to determine the cholesterol levels and the activity of transaminases (AST and ALT) or epididymal alkaline phosphatase (ALP). Histological study of testicular tissue was also undertaken to examine the α-CP-induced ultrastructural changes using transmission electron microscopy (TEM). α-CP significantly (P<0.05) increased the activities of testicular AST (1.36±0.12 vs. 1.19±0.10), ALT(1.78±0.11 vs. 1.36±0.09), and significantly (P<0.05) decreased the testosterone levels (0.86±0.24 vs. 1.72±0.18). Testicular cholesterol levels were elevated in treated animals as compared to control (1.81±0.16 vs. 1.42±0.08). Epididymal alkaline phosphatase (ALP) activity was also decreased significantly (P<0.05) in treated animals (1.10±0.20 vs. 1.64±0.1). Histological studies on day 28 revealed rupture of spermatogonic cell membrane, shrinkage in the nucleus, stages of apoptosis, condensation of chromatin, and decreased cytoplasmic organelles. The study suggested that short-term exposure to α-CP in albino mice induced toxicopathological lesions in testicular tissue leading to decreased plasma testosterone levels.
