Systemic Lithium Chloride Administration Improves Tooth Extraction Wound Healing in Estrogen-Deficient Rats

Abstract

The purpose of this investigation was to evaluate the effects of lithium chloride (LiCl) on the socket healing of estrogen-deficient rats. Seventy-two rats were allocated into one of the following groups: Control, Ovariectomy and LiCl (150 mg/kg/2 every other day orally) + Ovariectomy. Animals received LiCl or water from the 14th day post-ovariectomy, until the completion of the experiment. On the 21st day after ovariectomy, the first molars were extracted. Rats were euthanized on the 10th, 20th and 30th days following extractions. Bone healing (BH), TRAP positive cells and immunohistochemical staining for OPG, RANKL, BSP, OPN and OCN were evaluated. The Ovariectomy group presented decreased BH compared to the LiCl group at 10 days, and the lowest BH at 20 days (p<0.05). At 30 days, the Ovariectomy and LiCl-groups presented lower BH than that of the Control (p<0.05). The number of TRAP-stained cells was the lowest in the LiCl group at 20 days and the highest in the Ovariectomy group at 30 days (p<0.05). At 10 days of healing, the LiCl group demonstrated stronger staining for all bone markers when compared to the other groups, while the Ovariectomy group presented higher RANKL expression than that of the Control (p<0.05). LiCl enhanced bone healing in rats with estrogen deficiency, particularly in the initial healing phases. However, as data on the effects of lithium chloride on bone tissue are still preliminary, more studies related to its toxicity and protocol of administration are necessary before its application in clinical practice.

Ion incorporation into bone grafting materials

“…42 It is known to enhance bone formation by activating both the Sonic hedgehog (SHH) and Wnt/β-catenin pathways and by stabilizing βcatenin through the inhibition of glycogen synthase kinase 3 (GSK-3b) activity. [43][44][45][46] Furthermore, Li + promotes the proliferation of endothelial cells and stimulates the release of pro-angiogenic growth factors by triggering the Wnt/β-catenin signaling cascade. Various biomaterials have incorporated lithium, and research indicates that the inclusion of Li ions can bolster bone formation and regenerate new bone, as observed in femoral cartilage defects in New Zealand white rabbits (Figure 3).…”

“…Lithium (Li), a trace element in human bones, has garnered attention in bone regeneration due to its pivotal role in osteogenesis 42 . It is known to enhance bone formation by activating both the Sonic hedgehog (SHH) and Wnt/β‐catenin pathways and by stabilizing β‐catenin through the inhibition of glycogen synthase kinase 3 (GSK‐3b) activity 43–46 . Furthermore, Li + promotes the proliferation of endothelial cells and stimulates the release of pro‐angiogenic growth factors by triggering the Wnt/β‐catenin signaling cascade.…”

Li-Doped Bioactive Ceramics: Promising Biomaterials for Tissue Engineering and Regenerative Medicine

“…Higher bone volume, trabecular thickness, trabecular number, and osseointegration were assessed with Micro-CT, and the maximum push-out force (N) and implant−bone contact shear strength (N/mm 2 ) were stronger in the LiCl group (36 ± 6 N vs. 105 ± 12 N, 1.9 ± 0.4 vs. 5.6 ± 0.7 N/mm 2 , respectively) [ 131 ]. The effects of systemic LiCl administration on the socket healing of estrogen-deficient rats were evaluated, finding that LiCl improved bone regeneration in rats with estrogen deficiency, especially in the initial healing [ 132 ]. Bone regeneration by Li treatment is therefore dose-dependent and the dosage may be dependent on the stem cell source [ 133 ].…”