Abstract
Cyclosporin A (CsA) is used as an immunosuppressive agent and its prominent side effect is the induction of gingival overgrowth, which remains a significant problem. The risk factors appraised include the duration of treatment. However, there are no stereological and biochemical studies exploring the effects of long-term CsA therapy on gingival tissue. The purpose of the present study was to investigate the level of TGF-beta1 in saliva and describe the densities of fibroblasts and collagen fibers in the gingival tissue of rats treated with CsA for long periods. Rats were treated for 60, 120, 180 and 240 days with a daily subcutaneous injection of 10 mg/kg of body weight of CsA. At the end of the experimental periods, saliva was collected for the determination of TGF-beta1 levels. After histological processing, the oral epithelium and the connective tissue area were measured as well as the volume densities of fibroblasts (Vf) and collagen fibers (Vcf). After 60 and 120 days of CsA treatment, there was a significant increase in Vf and Vcf as well as a significant increase in TGF-beta1 levels. After 180 and 240 days, reduction in the gingival overgrowth associated with significant decreases in the level of TGF-beta1, and also decreased Vf and Vcf, were observed. The data presented here suggest that after long-term therapy, a decrease in TGF-beta1 levels occurs, which might contribute to an increase in the proteolytic activity of fibroblasts in the gingiva, favoring the normality of extracellular matrix synthesis.
Highlights
Cyclosporin A (CsA) is a cyclic undecapeptide that was initially isolated from the fungus Tolypocladium inflatum gams[12]
The purpose of the present study was to investigate the level of TGF-β1 in saliva and describe the densities of fibroblasts and collagen fibers in the gingival tissue of rats treated with CsA for long periods
Gingival overgrowth was seen in all gingival areas, but it was more evident on the buccal gingival tissue of the lower molar teeth
Summary
Cyclosporin A (CsA) is a cyclic undecapeptide that was initially isolated from the fungus Tolypocladium inflatum gams[12]. The use of CsA as an immunosuppressant has revolutionized organ transplantation, which has become the management of choice for many patients with chronic and life-threatening conditions[8]. CsA has been used for the treatment of type 2 diabetes, rheumatoid arthritis, psoriasis, multiple sclerosis, malaria, sarcoidosis, and several other diseases with an Spolidorio LC, Spolidorio DMP, Holzhausen M, Nassar PO, Nassar CA. Effects of long-term cyclosporin therapy on gingiva of rats – analysis by stereological and biochemical estimation. Braz Oral Res 2005;19(2):[112-8]. CsA’s main side effects include nephrotoxicity, hepatic dysfunction, neurological disturbances and hypertension[12,18]. The most prominent side effect of CsA therapy in oral tissues is gingival overgrowth[11,19,21]
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