South Asian cocktail disrupts testicular integrity, Steroidogenesis and Spermatogenesis by Targeting Steroidogenic Enzymes and germ cells via an Oxidative Stress Mediated Pathway

Globally, the South Asian Cocktail (SAC), a substance of abuse, is becoming popular. The effects of SAC on male fertility are unknown; however, its component pharmaceuticals, such as codeine, rohypnol, and promethazine, have been linked to male infertility. Thus, this study assessed SAC's influence and putative mechanisms on male fertility among SAC consumers. Fifty adult male Wistar rats were randomly split into five groups (n = 10): control (5 ml D. H₂0); codeine group (5 mg/kg), rohypnol (4 mg/kg), promethazine (50 mg/kg), and SAC group (codeine 5 mg/kg, rohypnol 4 mg/kg, and promethazine 50 mg/kg). The administration was via gavage for 56 days. Animals were sacrificed under intraperitoneal ketamine (4 mg/kg) and xylazine (40 mg/kg). We obtained blood samples via cardiac puncture and centrifuged them to obtain serum for biochemical analysis. We removed and weighed the testes, epididymis, prostate, and seminal vesicle. The samples were tested for oxidative stress markers, cytokines, and apoptotic markers using ELISA. There were elevated levels of oxidative stress, xanthine oxidase/uric acid levels, inflammation, and cell death resulting in compromised steroidogenesis and spermatogenesis and diminished sperm quality. This study revealed that SAC exposure might impair testicular function via oxidoreductase and TNF-α and IL1-β, and activation of caspase-3 signaling pathway.