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
DOI : 10.62610/RJOR.2024.1.16.31
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.