Influence of Orchiectomy on Sex-Specific Responses to Aristolochic Acid-Induced Renal Injury | Recent Developments in Chemistry and Biochemistry Research Vol. 7

Aristolochic acid (AA) is widely recognized for its nephrotoxic effects; however, the role of sex in AA-induced renal injury remains ambiguous. The present investigation aimed to elucidate the sex-based disparities in renal dysfunction and tubular damage resulting from AA exposure. Male and female murine models underwent bilateral orchiectomy and ovariectomy, respectively. Fourteen days post-gonadectomy, the subjects were administered AA (10 mg/kg body weight/day) via intraperitoneal injection for two consecutive days, followed by euthanasia seven days subsequent to the initial injection. Parameters such as body weight, renal functionality, and tubular morphology were meticulously evaluated. A comparative analysis between male and female non-gonadectomized subjects revealed that the weight reduction induced by AA was significantly more pronounced in male mice (H = 20.041, dF = 3, P ≤ 0.001, as determined by the Kruskal-Wallis test). Additionally, functional and structural impairments in male kidneys were significantly exacerbated following AA administration, whereas the kidneys of AA-treated female mice exhibited either negligible or mild injuries (F = 83.618, P < 0.001 on plasma creatinine level; F = 3971.979, P < 0.001 on tubular injury score in the cortex, as determined by the analysis of variance). Ovariectomy did not influence AA-induced nephrotoxic acute kidney injury in the female cohort (F = 0.0955, P = 0.760 on body weight change; F = 0.211, P = 0.651 on plasma creatinine level; F = 2.985, P = 0.099 on tubular injury score in the cortex, as determined by the analysis of variance). In contrast, orchiectomy resulted in a significant attenuation of weight loss, renal dysfunction, and tubular damage in the context of AA-induced nephrotoxicity among male mice (F = 8.541, P = 0.008 on body weight change; F = 8.892, P = 0.007 on plasma creatinine level, as determined by the analysis of variance; H = 19.767, dF = 3, P ≤ 0.001 on tubular injury score in the cortex, as determined by the Kruskal-Wallis test). This research has conclusively established that the presence of testes contributes to the development of AA-induced nephrotoxic acute kidney injury. Future studies should investigate the molecular mechanisms by which gonadal hormones, such as androgens and estrogens, modulate AA-induced nephrotoxicity. Additionally, researchers should explore sex-specific therapeutic strategies, which may pave the way for translating these findings into clinical trials.

 

Author (s) Details

Jinu Kim
Department of Anatomy, College of Medicine, Jeju National University, Jeju 63243, Republic of Korea and Interdisciplinary Graduate Program in Advanced Convergence Technology & Science, Jeju National University, Jeju 63243, Republic of Korea.

 

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