The effect of systemic Isotretinoin on salivary tissue inhibitors of metalloproteinases 1 and 2 and salivary flow rate in periodontal disease

Aims: To evaluate and compare changes in salivary flow rate and salivary levels of TIMP-1 and TIMP-2 in individuals taking oral Isotretinoin (INN) with those who do not take INN. To assess the variation in TIMP1 and TIMP-2 as well as salivary flow rate observed at different stages of periodontal disease in comparison to those observed in the case of healthy periodontium. Materials and methods: An examiner-blind case-control study involving 180 human adults divided into six groups based on their periodontal status. Clinical parameters, including pocket depth, clinical attachment level, and bleeding on probing were measured at six sites per tooth. Whole unstimulated saliva samples were collected from all subjects to evaluate salivary flow rate (SFR). Salivary TIMP-1 and TIMP-2 levels were detected using enzyme-linked immunosorbent assay (ELISA). Data were analyzed using IBM SPSS Software. The Kruskal Wallis test and Mann-Whitney U-tests were employed to verify any significant differences between the groups for all parameters. Multi-regression analysis was performed for each parameter tested in each group. All tests were compared at a significance level of 0.05. Results: SFR was statistically significantly lower among all INN groups in comparison to the control groups (P < 0.001). TIMP-1 and TIMP-2 were significantly higher in all INN groups in comparison to the control groups, in both gingivitis cases (P = 0.004, P < 0.0001 respectively) and periodontitis cases (P < 0.0001). Conclusion: Although INN reduces salivary flow rate, the findings of the present study revealed that it had an anti-inflammatory effect in periodontal biomarkers. Specifically, it was positively correlated with an elevation of salivary TIMP-1 and TIMP-2. Hence, INN might be a future additive medication to be further evaluated for the treatment of periodontal diseases. (C) 2021 The Authors. Published by Elsevier B.V. on behalf of King Saud University.