Background: Quinine (QU) as an anti-malarial drug induces alterations in testicular tissue. Toxic effects of monosodium glutamate (MSG) on the male reproductive system have been recognized.

Objective: To investigate the impact of MSG administration on the intensity of gonadotoxicity of QU.

Materials and methods: Sixty eight-wk old Wistar rats weighing 180-200 gr were divided into six groups (n = 10/each): the first group as a control; the second and third groups received low and high doses of MSG (2 & 4 gr/kg i.p.), respectively, for 28 days; the fourth group received QU for seven days (25 mg/kg); and in the fifth and sixth groups, QU was gavaged following the MSG administration (MSG + QU) from day 22 to day 28. Serum testosterone and malondialdehyde (MDA) levels were measured. Testes samples were prepared for tissue MDA levels, histomorphometry, and immunohistochemistry of p53. Sperm analysis was performed on cauda epididymis.

Results: Serum and tissue MDA levels were increased in treated groups compared to the control group. This increment was higher in the MSG + QU groups. The testosterone levels were reduced significantly (p $<$ 0.0001) in all treated groups. In addition, histomorphometric indices and tubular epithelium population were reduced significantly (p $<$ 0.0001) in QU, MSG + QU, and consequently in high-dose MSG, QU, MSG + QU groups. All spermatogenic indices were reduced in the treated groups, particularly in the MSG + QU groups. Sperm motility and viability indices were reduced significantly (p = 0.003) in the MSG + QU groups. Finally, the overexpression of p53 was observed in the MSG + QU groups.

Conclusion: The administration of MSG before and during QU therapy may intensify testicular tissue alterations.