Background and Objective
After tooth extraction, the extraction socket undergoes several steps of soft and hard tissue healing. The healing process of the extraction socket is modulated by a range of signaling factors and biochemical agents. It has been reported that resveratrol, a polyphenolic compound, exhibits various biological effects, including anti‐inflammatory, anti‐carcinogenic, antioxidant, and anti‐aging effects, and protects cardiovascular and bone tissues. In this study, we examined the cellular effects of resveratrol on human periodontal ligament (hPDL) cells and osteoblast‐like (MC3T3‐E1) cells and evaluated the bone‐healing capacity of tooth extraction sockets in mice.
Material and Methods
Resveratrol was applied to hPDL and MC3T3‐E1 cells to detect cell proliferation and alkaline phosphatase (ALP) activity, and qPCR was employed to understand the gene expression level in vitro. For in vivo experiment, six‐week‐old C57BL/6 male mice were randomly divided into control (n = 15) and experimental (n = 15) groups and maxillary first molars were extracted by surgery. Experimental groups received 50‐µM resveratrol on extraction sockets and analyzed the degree of new bone formation.
Results
Treatment of hPDL and MC3T3‐E1 cells with resveratrol increased the cell proliferation and ALP activity and enhanced the expression of ALP, BMP‐2, BMP‐4, and OC genes. Resveratrol enhanced new bone formation in the lingual extraction socket in mice.
Conclusion
These results suggest that resveratrol increases the cellular physiology of PDL and osteoblast including their proliferation and differentiation and may play an important role in bone‐healing capacity after tooth extraction.
The combination of calcium channel blockers (CCB) and angiotensin receptor blockers (ARB) for the treatment of hypertension showed improved efficacy and safety. Amlodipine is mainly metabolized by cytochrome P450 (CYP) 3A4, whereas losartan is metabolized by CYP2C9 and CYP3A4. The potential pharmacokinetic interactions between amlodipine and losartan were assessed. An open‐label, three‐period, fixed‐sequence trial was conducted. Amlodipine, losartan and combined amlodipine and losartan were administered to 24 healthy male participants during periods 1, 2 and 3, respectively, for 9 days each. The pharmacokinetics of amlodipine, losartan and EXP‐3174, an active metabolite of losartan, were assessed at steady‐state. Twenty participants completed the study without serious adverse events. Losartan did not influence the exposure of amlodipine at steady‐state (AUCτ, 165.15 ng h/mL [amlodipine alone] vs 172.36 ng h/mL [combination], P = 0.389) [geometric mean ratio (GMR) (90% confidence interval [CI]), 1.060 (0.954‐1.178)]. In addition, the exposure of EXP‐3174 was not affected by amlodipine (AUCτ, 1159.46 ng h/mL vs 1105.10 ng h/mL, P = 0.295) (GMR [90% CI], 0.957 [0.891‐1.027]). However, amlodipine significantly decreased the exposure of losartan at steady‐state (AUCτ, 1241.50 ng h/mL vs 1082.02 ng h/mL, P = 0.006) (GMR [90% CI], 0.875 [0.813‐0.942]) and increased oral clearance of losartan (84.65 L/h vs 97.26 L/h, P = 0.002). Combination use of two drugs caused additive haemodynamic changes compared to treatment of amlodipine or losartan alone. The co‐administration of amlodipine and losartan was tolerable and did not cause substantial pharmacokinetic interaction, even though losartan disposition was affected. Combination use of the two drugs caused additive haemodynamic changes compared to monotherapy of amlodipine or losartan.
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