Glycyrrhizin alleviated cisplatin-induced testicular injury by inhibiting the oxidative, apoptotic, hormonal, and histological alterations

Am J Vet Res. 2024 Nov 7;86(1):ajvr.24.10.0288. doi: 10.2460/ajvr.24.10.0288. Print 2025 Jan 1.

Abstract

Objective: To evaluate the potential contribution of glycyrrhizin (GLZ) to mitigate the testicular toxicity linked to cisplatin (CIS) intoxication.

Methods: 40 mature male Wistar albino rats (Rattus norvegicus albinus) were randomly divided into 4 equal groups (n = 10) for 60 days: the control group, CIS-treated group (single dose of 7 mg/kg, IP), GLZ-treated group (25 mg/kg, PO), and GLZ plus CIS-treated group. Blood and testis samples were examined using biochemical, histological, and immunohistochemical techniques. Semen samples were also obtained, and any abnormalities were reported.

Results: Serum follicle-stimulating hormone, luteinizing hormone, and testosterone levels were all markedly reduced by CIS. Oxidative stress and a significant reduction in levels of the antioxidant enzymes glutathione peroxidase, superoxide dismutase, and catalase were linked to CIS. Immunohistochemically, CIS showed diffuse, significantly positive immunolocalizations against the anti-caspase 3 antibody, indicating widespread apoptosis within the testicular parenchyma. Histopathologically, CIS showed diffuse coagulative necrosis of spermatogenic cells, necrotic Sertoli cells, intertubular edema, and Leydig cell hyperplasia. Moreover, CIS revealed a noteworthy increase in sperm abnormalities. Pre-coadministration and posttreatment with GLZ mitigated the majority of these detrimental consequences, and serum levels of antioxidant enzymes, luteinizing hormone, follicle-stimulating hormone, and testosterone were significantly elevated.

Conclusions: Glycyrrhizin has been proven to be a strong antioxidant as well as antiapoptotic and cytoprotective against CIS testicular damage.

Clinical relevance: The described model is a tool to evaluate the testicular protective impact of GLZ.

Keywords: antioxidants; apoptosis; cisplatin; glycyrrhizin; testicular toxicity.

MeSH terms

  • Animals
  • Antineoplastic Agents / adverse effects
  • Antioxidants
  • Apoptosis* / drug effects
  • Cisplatin* / adverse effects
  • Follicle Stimulating Hormone / blood
  • Glycyrrhizic Acid* / pharmacology
  • Glycyrrhizic Acid* / therapeutic use
  • Luteinizing Hormone / blood
  • Male
  • Oxidative Stress* / drug effects
  • Random Allocation
  • Rats
  • Rats, Wistar*
  • Testicular Diseases / chemically induced
  • Testicular Diseases / pathology
  • Testicular Diseases / prevention & control
  • Testicular Diseases / veterinary
  • Testis* / drug effects
  • Testis* / pathology
  • Testosterone / blood

Substances

  • Glycyrrhizic Acid
  • Cisplatin
  • Testosterone
  • Antineoplastic Agents
  • Follicle Stimulating Hormone
  • Luteinizing Hormone
  • Antioxidants