Rosmarinic acid reverses the effects of metronidazole-induced infertility in male albino rats

Abstract

Rosmarinic acid (RA) is a natural antioxidant that has many biological activities. In the present study we investigated the potential of RA to reverse the negative effects of the widely used antibiotic and antiprotozoal agent metronidazole (MTZ), which is known to induce reversible male infertility. Two doses of RA (5 and 15mg kg) were studied in sexually mature rats with and without MTZ-induced infertility. Rats were intraperitoneally injected with 5mg kg RA or 15mg kg RA (in distilled water) and, 45min later, they were intraperitoneally injected with 40mg kg MTZ (in distilled water). Cauda epididymidal sperm suspensions were used to assess sperm count, motility and morphology. Histological and ultrastructural studies were performed on the testes and cauda epididymidis. In rats in which infertility was not induced, neither dose of RA affected the parameters assessed. However, in sexually mature rats in which infertility was induced by 40mg kg MTZ, RA at both 5 and 15mg kg ameliorated the damaging effects of MTZ on final bodyweight (30 days later), sperm motility and morphology. Only 5mg kg RA, and not 15mg kg RA, improved the harmful effects of MTZ on the sperm count and testis ultrastructure. The findings of the present study have considerable clinical implications and suggest a possible use for RA to reverse the negative effects of MTZ on male fertility, the male reproductive system and spermatogenesis.

Rosmarinic acid improves boar sperm quality, antioxidant capacity and energy metabolism at 17°C via AMPK activation

“…RA is a water-soluble polyphenolic phytochemical with free-radical scavenging and antioxidant effects (Veras et al, 2019). Al-Alami et al (2017) showed that RA had a reversal effect on metronidazole-induced infertility in male albino rats. In the present study, tegrity.…”

“…Al‐Alami et al. (2017) showed that RA had a reversal effect on metronidazole‐induced infertility in male albino rats. In the present study, supplementation of RA in the extender effectively improved stored boar sperm motility, plasma membrane integrity and acrosomal integrity.…”

Thiamine deficiency and oxidative stress induced by prolonged metronidazole therapy can explain its side effects of neurotoxicity and infertility in experimental animals: Effect of grapefruit co-therapy

“…These findings are in line with those of many researchers. 4,13,15,26,[30][31][32] These spermatotoxic effects of MTZ can be partially explained by the fact that MTZ crosses the BTB and negatively affects the germ cells in the seminiferous tubules, with subsequent decreased secretion of testosterone. 15,32 However, the mechanism of the inhibitory effect of MTZ on reproductive hormones (gonadotrophins and testosterone) is still unclear.…”

“…Previously, prolonged MTZ therapy was shown to induce reversible, unwanted effects on male fertility, reproductive hormone levels and sperm motility and/ or the sperm count. [2][3][4] This MTZ-induced infertility has been shown to be prevented by supplementation with natural compounds that are known to have antioxidant activity. 3,4 MTZ-associated neurotoxicity has been reported in both humans and veterinary species, including rats.…”

“…[2][3][4] This MTZ-induced infertility has been shown to be prevented by supplementation with natural compounds that are known to have antioxidant activity. 3,4 MTZ-associated neurotoxicity has been reported in both humans and veterinary species, including rats. 5,6 The mechanism of MTZ-induced neurotoxicity is still unclear, but several hypotheses have been presented: one suggests that MTZ binds to RNA with subsequent inhibition of protein synthesis in neurons 7 ; another proposes that MTZ forms toxic reactive oxygen species through interactions with neurotransmitters 8 ; and yet another suggests that MTZ antagonizes the effect of thiamine.…”