# Effects of Lithium Chloride and Nitric Oxide Inhibitor on Orthodontic Tooth Movement in the Rat
## 4 Discussion  
Orthodontic tooth movement is an established clinical approach to bring teeth in the desired position, a therapy that uses forces to initiate cellular events culminating in the resorption and formation on the pressure and tension site, respectively [1; 2]. However, it is a clinical challenge to predict the speed of tooth movement, and ideally even to find therapeutic approaches to speed up the process. Progress in clinical orthodontics is based on the fundaments of preclinical research where the mechanisms of OTM are evaluated in the light of pharmacological therapies; some therapies are maybe not intentionally affecting bone remodeling, but as a side effect, they do. One example depicted in the present study is LiCl, a commonly prescribed drug for patients suffering from mental disorders [6]. Based on the knowledge that LiCl prevents bone resorption in ovariectomized osteopororotic rat models and thus bone resorption [7], it is not surprising that LiCl reduces OTM in rat models [9], observation that are supported by the findings reported here. Further, in support of what we report here are observations showing blocking of nitric oxide by means of the inhibitor L-NAME not only reduced ovariectomy-induces osteopororotic bone loss in the rat model [18] but also had a blocking effect on OTM [15; 16]. Overall, the findings we have are supporting previous knowledge and providing a solid basis for the actual research hypothesis we have proposed. Based on the previous observations, we have now asked if the inhibition of OTM induced by LiCl and by L-NAME are synergistic or even dependent on each other. The support for this assumption comes from the findings that co-administration of LiCl and L-NAME have additive effects on reducing morphine withdrawal syndromes in mice [19]. There is thus a reason to ask if LiCl requires the NOS activity to reduce tooth movement. However, we have to reject this hypothesis because the suppression of OTM induced by LiCl and by L-NAME was not synergistic and also without any kinds of dependency. In support of these new observations are the data from changes in thyroid hormones levels observed with LiCl but not with L-NAME, resulting in a robust and significant increase of TSH and decrease of T3 and T4 in the LiCl-treated rats only. Thus, it seems that the antihyroid effects of LiCl are independent of NOS activity. Considering that 5-thyroxine [23] and L-thyroxin [24] stimulated OTM and thyroid hormones excess accelerates bone turnover with predominant bone resorption [36], the known LiCl-mediated reduction of thyroid hormones [37] maybe culminates in the reduced tooth movement. Even the therapeutic effects of LiCl in mania and depression are thought to be mediated mainly via thyroid hormones [38]. In support of previous observations, numerous studies have confirmed a particular association between serum TSH levels and obesity [39]. Again, our findings nicely match those of others, adding the novelty that the reduction of OTM induced by LiCl may be mediated via thyroid hormones but not nitric oxidase activity. The study has limitations. Rat model not necessary represents the complex situation in patients undergoing OTM and it does not provide the real clinical scenario of the patients suffering from mental disorders under the treatment with LiCl [6]. Moreover, the clinical relevance of our findings with L-NAME should be interpreted with care as L-NAME is an experimental antihypotensive agent that has not yet received the FDA approval. Nevertheless, it is important to understand the molecular mechanism of OTM to take advantage of this knowledge for future stimulation of this process. Another limitation is that we have no robust information on the resorption of the tooth roots and how LiCl and L-NAME change this osteoclastic event. This should be considered in future studies. Future research should further investigate if it is the diminished thyroid hormones levels that are responsible for the decreased OTM in response to LiCl treatment.