Dapagliflozin prevents reproductive damage caused by acute systemic inflammation through antioxidant, anti‐inflammatory, and antiapoptotic mechanisms

• Published in: Basic & clinical pharmacology & toxicology 2024-11, Vol.135 (5), p.561-574
• Main Authors: Topsakal, Senay, Ozmen, Ozlem, Asci, Halil, Gulal, Abdurrahman, Ozcan, Kadriye Nilay, Aydin, Bunyamin
• Format: Article
• Language: English
• Subjects: Animals; Anti-Inflammatory Agents - pharmacology; Antioxidants; Antioxidants - pharmacology; Apoptosis - drug effects; Aquaporin 4; Benzhydryl Compounds - pharmacology; Damage assessment; Damage prevention; dapagliflozin; Diabetes mellitus; Edema; Fallopian tube; Female; female reproductive system; Females; Genetic analysis; Genital tract; Genitalia, Female - drug effects; Genitalia, Female - pathology; Glucosides - pharmacology; Hemorrhage; Hyperemia; Inflammation; Inflammation - drug therapy; Inflammation - prevention & control; Leukocytes (neutrophilic); lipopolysaccharide; Lipopolysaccharides; Lipopolysaccharides - toxicity; NLR Family, Pyrin Domain-Containing 3 Protein - metabolism; Ovaries; Ovary - drug effects; Ovary - metabolism; Ovary - pathology; Oxidants; Oxidative stress; Oxidative Stress - drug effects; Oxidizing agents; Rats; Rats, Wistar; Reproductive system; Sodium-glucose cotransporter; Sodium-Glucose Transporter 2 Inhibitors - pharmacology; Tubes; Uterus; Uterus - drug effects; Uterus - pathology
• ISSN: 1742-7835; 1742-7843; 1742-7843
• DOI: 10.1111/bcpt.14077

Dapagliflozin (DPG) is a sodium‐glucose cotransporter‐2 (SGLT2) inhibitor that has been suggested to possess anti‐inflammatory properties in diabetes. The aim of this study is to evaluate the role of DPG administration in preventing lipopolysaccharide (LPS)‐induced damage in the female genital system. Thirty‐two female Wistar Albino rats were randomly allocated into four groups: control group, LPS group, LPS + DPG group and DPG group. At the end of the experimental phase, ovary, fallopian tube and uterus tissues were collected for histopathological, immunohistochemical, genetic and biochemical analyses. The findings showed that LPS caused histopathological changes characterized by marked hyperaemia, mild to moderate haemorrhage, oedema and neutrophil leucocyte infiltrations and degenerative and necrotic changes in the female genital tract. In addition, it decreased total antioxidant status (TAS), increased total oxidant status (TOS) and oxidative stress index (OSI) levels. LPS also increased the expressions of Cas‐3, G‐CSF and IL‐1β in the ovary, fallopian tubes and uterus immunohistochemically. While Claudin‐1 expression decreased, NLRP3 and AQP4 gene expressions increased due to LPS. However, DPG treatment prevented all these changes. The results of this study indicate that, DPG can be used to prevent LPS‐induced lesions in the female reproductive system.