The role of autophagy in paclitaxel and cremophor induced damage to rat testis

Abstract

ABSTRACT The anticancer drug, paclitaxel (PTX), is used to treat a variety of solid tumors, but its effects on normal tissues remain unclear. We investigated the effects of different doses of PTX and its vehicle, cremophor EL, on testis using histochemical, immunohistochemical and biochemical methods. We used 30 adult Wistar albino rats divided randomly into five groups: physiological saline was administered to the control group; the sham 8 group received 8 mg/kg cremophor EL; the sham 16 group received 16 mg/kg cremophor EL; 8 mg/kg PTX was administered to the PTX 8 group; and the PTX 16 group received 16 mg/kg PTX. The cremophore content in PTX groups was the same as in the sham group. All treatments were injected intraperitoneally (i.p.) once/week for 4 weeks. Tissue samples were excised 24 h after the last injection. Tissue sections were prepared and hematoxylin and eosin staining was performed to assess testicular morphology. Expression of Beclin-1, LC3A/B and P62 were assessed using immunohistochemistry. Serum and tissue testosterone levels were determined using ELISA. Light microscopy revealed seminiferous tubule damage, irregularities in germinal epithelium and decreased seminiferous tubule diameter in the PTX treated groups. The immunoreactivity of Beclin-1, LC3A/B, and P62 was increased significantly in the PTX groups compared to the control group. Cremophor EL alone damaged the testis, although not as much as PTX. PTX caused significant damage to testicular tissue and increased autophagy of spermatogenic cells; cremophore EL also may play a role in this effect.