Sex Difference in Gentamicin‑induced Nephrotoxicity: Influence of L‑arginine in Rat Model

Abstract

Background: L‑arginine is an important precursor for the formation of nitric oxide (NO). According to previous studies, NO function is related to gender. Likewise, chronic renal diseases have lower prevalence in female. Gentamicin (GM) is an aminoglycoside antibiotic. According to some studies, males are more sensitive to GM renal nephrotoxicity. This study attempts to fnd protective effects of L‑arginine on GM nephrotoxicity in male and female rats.

Methods: Male and female rats were divided into eight groups: Rats were randomly assigned to 8 groups each including both male and female rats. The frst and second groups received vehicle (saline), the third and fourth groups received gentamicin (80 mg/kg), the ffth and sixth groups received L‑arginine (150 mg/kg), and fnally, seventh and eighth groups received gentamicin+ L‑ arginine. Next, 9 days after administering drugs, blood samples were collected from the heart. After making sacrifces, the level of blood urea, creatinine (Cr), nitrite, and malondialdehyde (MDA) was measured in serums. Likewise, nitrite and MDA were measured in the homogenized kidney tissue.

Results: GM signifcantly increased serum level of urea and Cr in male and female rats (P < 0.05). However, co‑administration of GM + L‑arginine signifcantly did not decrease urea and Cr level in male rats, whereas, in female rats, they signifcantly reduced (P < 0.05). In response to GM, renal MDA level increased in male and female rats (P < 0.05), and in the presence of GM + L‑arginine, the level of MDA signifcantly decreased in both genders (P < 0.05).

Conclusions: L‑arginine demonstrated some protective effects
in female rats but did not protect against GM nephrotoxicity in male rats for unknown reasons, probably related to the effects of sex hormones which needs further studies to be confrmed.

Keywords: Gentamicin, L-arginine, Nephrotoxicity, Sex difference