Abstract
The study was undertaken to evaluate the safety of vitacamphorae (VCP) injection in Sprague-Dawley (SD) rats. Rats were intravenously administered with VCP at the doses of 0, 5, 15, and 50 mg/kg/day (equivalent to 0, 5, 15, and 50 times the clinical equivalent dose) for 4 weeks, respectively. In addition, we also tested oxidative stress-related parameters and cytokine levels in rat serum. In the current study, intravenous administration of VCP at a dose of 50 mg/kg/day caused significant pathophysiological responses in rats. Compared with the control group, different doses of VCP exposure had no significant effect on body weight, food consumption, and clinic pathology of rats after 4 weeks of VCP administration. Rats in high-dose group (50 mg/kg/day) showed general symptoms of convulsions after VCP administration. The toxicological significance of VCP exposure in the spleen of high-dose female rats was observed, which showed a significant increase in the relative spleen weights (P < 0.01) and mild lymphocyte proliferation in splenic pathology. Furthermore, the results of oxidative stress and cytokine detection showed that the levels of antioxidant enzymes SOD increased in each administration group, but the levels of a series of pro-inflammatory cytokines IL-1β, IL-6, IL-8, IL-12, and IFN-γ also increased in these groups. Above changes caused by VCP exposure can be reversed after 4 weeks of recovery. Overall, the results showed that the no-observed-adverse-effect-level (NOAEL) of VCP injection for 4-week toxicity was 15 mg/kg/day.
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This work was supported by Jiangsu Center for Safety Evaluation of Drugs. Thanks to Ms. Zhou for her guidance on this work and writing.
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Y Y, M S, Y L, J L, Y X, and B Z were involved in the design and performance of the experiments. Y Y, M S, and B Z drafted and revised the manuscript. All authors approved the final manuscript.
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The study related to animal was approved by Institutional Animal Care and Use Committee (IACUC) in Jiangsu center for safety evaluation of drugs. All operations are in compliance with ethical requirements and aiming to minimize the number of rats used and their suffering.
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Yuan, Y., Su, M., Liu, J. et al. Four-week intravenous repeated dose toxicity study of vitacamphorae injection in rats. Naunyn-Schmiedeberg's Arch Pharmacol 393, 2001–2007 (2020). https://doi.org/10.1007/s00210-020-01820-6
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DOI: https://doi.org/10.1007/s00210-020-01820-6