Morphological Assessment of Andrographolide-Induced Toxicity in the Epididymis and Testis of Wistar Rats

Abstract

Andrographolide (AG), a bicyclic diterpenoid lactone from Andrographis paniculata (AP), a Southeast Asian plant, is a medicinal herb in traditional Chinese medicine known for its anti-inflammatory properties and immune system reaction alteration.  This study was conducted to examine the impact of AG on testicular toxicity and epididymal spermatozoa in Wistar rats. AG was administered orally to male rats aged 90 days at a daily dosage of 50 mg/kg body weight over a period of 55 days. After the treatment period, light microscopy and transmission electron microscopy were utilized to examine the testis and epididymis. The results indicated that AG caused pathological changes in the testis and impacted the spermatozoa in the epididymis. The epididymal epithelium showed slight structural alterations due to AG exposure and damage arising from the testis and sperm. The changes observed comprised heightened endocytic activity in principal cells (PCs), an increase in the quantity of basal cells (BCs) and intraepithelial macrophages (IEMs), along with a more significant accumulation of lipofuscin within PCs, BCs, and IEMs. Furthermore, certain BCs appeared to evolve into cells similar to macrophages. Changes were also noted in the structure of clear cells (CCs). Additionally, the identification of tall, darkly stained columnar cells previously undetected in the rat epididymal epithelium appeared. Overall, AG has a detrimental impact on the testis and sperm, though this toxicity has been demonstrated to be reversible. The epididymal epithelium exhibited not only mild pathological alterations but also an increase in mechanisms designed to eliminate Sertoli cells (SCs) debris, defective or dead sperm, and prematurely released germ cells while simultaneously activating local immune responses.