Toxicology Reports (Jan 2022)
Gallic acid reverses ovarian disturbances in mice with letrozole-induced PCOS via modulating Adipo R1 expression
Abstract
Research question: Women are increasingly suffering from polycystic ovary syndrome (PCOS). Its pathophysiology is still unknown, though. The purpose of this study was to ascertain how gallic acid affected the pathophysiology of the ovary in an animal model of polycystic ovary syndrome. We also showed the potential mechanism of adiponectin involvement in endocrine metabolic changes in PCOS mice and the function of adiponectin, which appear to be frequent factors in PCOS. Design: Eighteen adult female Parkes strain mice (Age: 4–5 weeks) having body weight of 16–21 g were separated into three groups at random with 6 animals in each group as follows: Group I serving the control, received water and normal diet for 81 days; group II received oral gavage administration of letrozole (LETZ)(6 mg/kg b.w.daily), which was dissolved in 0.9 % NaCl solution for 21 days for the induction of PCOS and left untreated for 60 days; Group III received oral gavage administration of LETZ (6 mg/kg) for first 21 days followed by the administration of gallic acid (GA) (75 mg/kg b.w. orally daily) for 60 days. Results: We found LETZ-treated mice experienced PCOS-like symptoms, including increased Serum testosterone, LH/FSH ratio, body and ovarian weight, blood glucose, serum insulin levels and inflammatory Cytokines. We also found decreased serum estrogen, oxidant capacity and enzyme activity and altered ovarian cytoarchitecture, with multiple cysts apart from irregular estrous cycle. Furthermore, mRNA expression levels CYP11a, CYP19a1, Kitl, PTGS2 and Adipo R1 were decreased. Furthermore, LETZ-induced PCOS mice when treated with GA we observed decrease in testosterone, LH, LH/FSH ratio, blood glucose, serum insulin and inflammatory cytokines. GA treatment in PCOS mice also increased estrogen levels, and oxidant capacity as well as enzyme activity. Furthermore mRNA expression levels of CYP11a1, CYP19a1, KITL, PTGS2 and Adipo R1 were also increased in LETZ+GA treated mice. These changes were linked to lower levels of circulating adiponectin and were altered when the mice were administered with gallic acid. Conclusion: Gallic acid might be a potential therapy in treating PCOS by regulating endocrine and metabolic abnormalities that are brought on by a drop in adiponectin levels along with hyperandrogenism. Additionally, adiponectin seems to be a frequent factor in PCOS. In addition to reducing inflammation-related comorbidities linked to LETZ-induced PCOS, GA enhances mRNA expression levels CYP11a, CYP19a1, Kitl and PTGS2 and hence reduces endocrine and metabolic abnormalities.
