Role of oxidative stress in Cannabis sativa-associated spermatotoxicity: Evidence for ameliorative effect of combined but not separate melatonin and vitamin C

Abstract

The role of oxidative stress in Cannabis sativa (CS)-associated reproductive toxicity is inconclusive. The present study employed reactive oxygen species (ROS)-total antioxidant capacity (TAC) score to understand the effect of CS on oxidative stress, while the possible anti-oxidative effect of melatonin and vitamin C were also investigated in rats receiving them alone or together with cannabis. Fifty-four male albino rats were randomized to 9 oral treatment groups (n = 6) as follow: Groups I and II served as control and received 1 ml/kg normal saline and 10% ethanol (vehicle for CS administration) respectively. Groups III–V received melatonin (4 mg/kg), vitamin C (1.25 g/kg) and their combination respectively. Group VI received CS (2 mg/kg), while groups VII–IX received melatonin, vitamin C, and their combination respectively in addition to CS. All treatment lasted for 30 days. The CS reduced the sperm parameters, TAC, and the ROS-TAC score but increase the ROS, while only melatonin and/or vitamin C improved these parameters. Supplementation of rats receiving CS with either melatonin or vitamin C exacerbated the CS-induced oxidative stress and spermatotoxicity but their combination (melatonin + vitamin C) prevented these conditions in them. Furthermore, ROS-TAC score better predicted the condition of sperm than either TAC or ROS. In conclusion, this study further implicates oxidative stress in CS-induced spermatotoxicity using the ROS-TAC score. It also provides evidences for the preventive effect of melatonin and vitamin C on oxidative stress and sperm toxicity when combined but not when administered separately in rats receiving CS.

Keywords

• Cannabis sativa
• Melatonin
• Oxidative stress
• ROS-TAC score
• Spermatotoxicity
• Vitamin C