Lithium, a common component in various mood-stabilizing drugs, induces adverse effects on spermatozoa and human fertility. Oxidative stress, as a possible mechanism involved in lithium toxicity, can be reversed using antioxidants. Therefore, in this study, the effects of silymarin as a potent antioxidant were evaluated on human spermatozoa treated with lithium. Human spermatozoa were divided into five groups: (1) spermatozoa at 0 min, (2) spermatozoa at 180 min (control group), (3) spermatozoa treated with lithium chloride (500 μM) for 180 min, (4) spermatozoa were treated with silymarin (100 μM)+lithium chloride (500 μM) for 180 min, and (5) spermatozoa treated with silymarin (100 μM) for 180 min. Sperm motility and viability, the levels of malondialdehyde (MDA) and ferric reducing antioxidant power (FRAP), and the activity of antioxidant enzymes (catalase, superoxide dismutase, glutathione peroxidase) were evaluated in these groups. The results showed that sperm motility and viability significantly (p <0:001) decreased in the group treated with lithium. In addition, a significant increase (p <0:001) was observed in MDA levels, while FRAP amount and the activity of antioxidant enzymes decreased significantly (p <0:001) in this group. Interestingly, these results were significantly (p <0:001) reversed in the group treated with silymarin+lithium. The finding of the present study showed that oxidative stress plays a crucial role in lithium toxicity in human spermatozoa, and the coapplication of silymarin as a potent antioxidant with lithium can protect human sperm against oxidative stress-induced damage.
