Roxana Florentina Şufaru, M. C. Moraru, L. C. Gavril, Cătălina Anișoara Peptu, D. A. Chiran, D. V. Crauciuc, Ruxandra Vatavu, C. G. Lucasievici, Ruxandra Teodora Stan, Anca Sava
Abstract
We aim to study organ penetrability and anti-inflammatory effect of Hydrocortisone-loaded nanoparticles (HC-nano) after inducing hypertrophy with previous very-high dose medium-term Nifedipine administration. Materials and methods: Experiment was conducted in two phases on 60 adult, healthy Wistar rats, randomly divided initially in two groups (Phase 1), respecting 1:1 ratio between males and non-pregnant females, within each group. Group A1 (control) included 20 rats (10M/10F) and received no medication. Group B1 included 40 rats (20M/20F) and received oral Nifedipine 100 mg/kg body weight daily (approximately 100x therapeutic human dose), for 4 weeks. When Phase 1 ended, 8 rats did not survive in Group B1, and 40% (approximated to nearest integer) of rats of each sex, within each group were sacrificed, organs were harvested and analyzed microscopically. The rest of living rats entered Phase 2: Group A2 (control) remained with 12 rats (6M/6F) continuing with no medication; Group B2 counted 18 rats (10M/8F) that were given oral HC-nano 2 mg/kg body weight daily (therapeutic dose), for another 4 weeks. After Phase 2 completion, all animals were sacrificed, and tissues were microscopically analyzed. Results: Nifedipine induced statistically significant hypertrophy in the studied organs, with impressive results in gingiva (capillaries, p<0.01) and heart (muscle fibers, p<0.001), except the liver (centrilobular vein, p>0.05). Recorded hypergrowth did not differ significantly between sexes in Group B1, regardless of the organ (p>0.05), but 3 times more females died within Phase 1, due to very-high dose Nifedipine toxicity. After Phase 2, hypertrophy reduction was statistically significant in Group B2 (Hydrocortisone) compared with Group B1 (Nifedipine), in gums, heart (muscle fiber diameter) and kidneys (p<0.05), but still a noticeable level of inflammation persisted in gum and heart in comparison with control Group A2 (p<0.05). In the kidney, HC-nano anti-inflammatory effect was potent enough to obtain no statistical differences between Groups B2 and A2 (p>0.05). Conclusions: Very-high dose medium-term Nifedipine induces similar hypertrophic effects like chronic administration. Hydrocortisone-loaded nanoparticles have potent effects on several tissues in rats.
DOI : 10.6261/RJOR.2024.1.16.31
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