GnRH Agonist Triptorelin Induces Hepatic Fibrosis via Sex-Specific Oxidative and Inflammatory Responses in Adolescent Rats
Triptorelin treatment in adolescent rats leads to increased liver injury and fibrosis, with distinct responses observed between males and females. Further research in humans is needed to assess the relevance of these findings.
Where it sits
this study against the rest of the triptorelin corpusSummary and findings
This study measured the effects of GnRH agonist triptorelin on liver morphology and injury response in peripubertal male and female Sprague-Dawley rats at a dose of 100 μg subcutaneously. The findings indicated increased liver injury and fibrosis in both sexes, with distinct oxidative and inflammatory responses. Notably, biological females showed increased leukocyte infiltration, while biological males exhibited increased oxidative stress.
Abstract
Recently, GnRHa puberty blockers have been under scrutiny, with newly identified risks of heart and brain damage and recurrent concerns about fertility, cancer risk, and bone health. This study explores the effects of GnRHa on liver morphology, function, and injury response. Peripubertal male and female Sprague-Dawley rats received daily GnRHa triptorelin (100 μg) subcutaneously. Liver oxidative stress, inflammation, and fibrosis were evaluated via malondialdehyde and 8-OHdG (oxidative damage), immunohistochemistry for CK19 (cholangiocytes) and CD45 (leukocytes), and collagen staining as well as áSMA (liver fibrogenesis) and TIMP1 (extracellular matrix breakdown) expression, respectively. Following GnRHa treatment, only male rats exhibited increased ductular reaction and oxidative stress. In contrast, GnRHa-treated female rats showed increased leukocyte infiltration. In both sexes, GnRHa-treated rats showed increased fibrosis, with significantly increased collagen deposition and áSMA expression. Interestingly, GnRHa-treated female rats exhibited increased TIMP1 expression, whereas male rats showed decreased TIMP1 expression. Overall, GnRHa puberty blocking leads to significantly increased liver injury in both sexes. Specifically, biological females are at increased risk of hepatic inflammation, while biological males are at increased risk of oxidative stress. Human clinical trials are crucial for further exploring these findings.