The influence of prolactin-releasing prokinetic drugs on bone microarchitecture and biomechanics in streptozotocin-diabetic rat


ÖRÜN DEMİREL B., Akkoc A. N., Kilimci F. S., Gursoy S. N., Bekci F., Dost T., ...Daha Fazla

Acta Pharmaceutica Sciencia, cilt.63, sa.4, ss.882-895, 2025 (Scopus) identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 63 Sayı: 4
  • Basım Tarihi: 2025
  • Doi Numarası: 10.23893/1307-2080.aps6354
  • Dergi Adı: Acta Pharmaceutica Sciencia
  • Derginin Tarandığı İndeksler: Scopus, EMBASE
  • Sayfa Sayıları: ss.882-895
  • Anahtar Kelimeler: antidopaminergic drugs, diabetic gastroparesis, rational drug therapy, seconder osteoporosis, streptozocin
  • Eskişehir Osmangazi Üniversitesi Adresli: Evet

Özet

To understand the potential impact of antidopaminergics such as Domperidone (DOM), Metoclopramide (MCP), and Trimethobenzamide (TMB) used in diabetic gastroparesis, this study examined their effects—both harmful and beneficial—on bone fragility. A diabetic model was created in male Wistar rats by a single intraperitoneal injection of Streptozotocin (STZ, 60 mg/kg). Our groups consisted of: Control (no diabetes or treatment), STZ (diabetes) group, STZ+DOM (diabetes with DOM) group, STZ+MCP (diabetes with MCP) group, and STZ+TMB (diabetes with TMB) group. Treatments were administered daily during the last 2 weeks of the 8-week study. Bone biomechanical properties were evaluated using a three-point bending test (TPBT), while histopathological analysis and serum receptor activator of nuclear factor kappa-B ligand (RANKL) levels were also assessed. TPBT results indicated increased bone loss in the STZ group, and histological analysis revealed elevated lipid content in the femoral metaphysis. Rats in the STZ group showed significant alterations in bone biomechanical and histological parameters. Our study suggests that inducing diabetes with STZ in rats leads to bone loss within eight weeks, which may be valuable for testing new drugs aimed at treating osteoporosis in diabetic patients. Except for the doubling of RANKL levels with TMB among prolactin-releasing anti-dopaminergic agents in diabetic rats, these agents had no significant effect on bone mineral density or microarchitecture. Therefore, their use can be considered safe in sensitive diabetic populations.