Silymarin amplifies apoptosis in ectopic endometrial tissue in rats with endometriosis; implication on growth factor GDNF, ERK1/2 and Bcl-6b expression

Abstract

The present prospective study was done to evaluate the effect of silymarin (SMN) on endometriotic-like legions establishment and growth in experimentally-induced endometriosis. For this purpose, the experimental endometriosis was induced in 12 rats and then the animals subdivided into endometriosis-sole and SMN (50 mg kg−1, orally)+endometriosis groups. Following 28 days, the legions establishment, size, Glial cell line-derived neurotrophic factor (GDNF), gfrα1, B Cell Lymphoma 6 (Bcl-6b), Bcl-2, extracellular regulator kinase (ERK1/2) expression ratios, angiogenesis, the apoptosis and fibrosis indices were investigated. The SMN significantly (P < 0.05) decreased the enometriotic-like legions establishment and size, decreased mRNA levels of GDNF, gfrα1, Bcl-6b and Bcl-2 and remarkably diminished GDNF, gfrα1, Bcl-6b and Bcl-2-positive cells distribution/mm2 of tissue versus endometriosis-sole group. The SMN + endometriosis group exhibited a significant (P < 0.05) enhancement in ERK1/2 expression and represented diminished vascularized area and increased apoptosis and fibrosis indices, as well. In conclusion, the SMN by down-regulating GDNF and its receptor gfrα1 expression inhibits GDNF-gfrα1 complex generation and consequently suppresses Bcl-6b expression. Moreover, the SMN by enhancing the ERK1/2 expression and by suppressing the Bcl-2 expression promotes the apoptosis pathway. Finally, the SMN by down-regulating the angiogenesis ratio accelerates apoptosis and consequently induces severe fibrosis in endometriotic-like legions.