Mitigative Effects of l-Arginine and N-Acetyl Cysteine against Cisplatin-Induced Testicular Dysfunction and Toxicity through the Regulation of Antioxidant, Anti-inflammatory, and Antiapoptotic Markers: Role of miR-155 and miR-34c Expression

Fatma A Gad ¹, Mahmoud Abdelghaffar Emam ², Abeer A Eldeeb ³

⁰Clinical Pathology Department, Faculty of Veterinary Medicine, Benha University, P.O. Box13736 Benha, Egypt.

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July 1, 2024

View abstract on PubMed

Summary

N-acetyl cysteine (NAC) and l-arginine (LA) protect against cisplatin-induced testicular dysfunction by regulating oxidative stress, inflammation, and apoptosis. These compounds modulate micro-RNA (miRNA) expression, offering a potential therapeutic strategy for chemotherapy side effects.

Area Of Science

Reproductive Biology
Pharmacology
Molecular Biology

Background

Cisplatin (CIS) chemotherapy commonly causes testicular dysfunction.
Micro-RNAs (miRNAs), specifically miR-155 and miR-34c, are implicated in CIS-induced testicular toxicity.
N-acetyl cysteine (NAC) and l-arginine (LA) are investigated for their protective potential.

Purpose Of The Study

To investigate the role of miR-155 and miR-34c in cisplatin-induced testicular dysfunction.
To evaluate the protective effects of N-acetyl cysteine (NAC) and/or l-arginine (LA) against CIS toxicity.
To assess the impact of NAC and LA on oxidative stress, inflammation, apoptosis, and miRNA expression in the testes.

Main Methods

Albino rats were divided into seven groups: control, CIS, NAC, LA, NAC+CIS, LA+CIS, and NAC+LA+CIS.
CIS was administered once, while NAC and LA were administered daily for 28 days.
Serum hormone levels, testicular enzyme activities, oxidative stress biomarkers, inflammatory cytokines, and apoptosis markers were measured.
Histopathological and immunohistochemical analyses were performed, including PCNA, F4/80, and BAX expression.
Expression levels of miR-155 and miR-34c were analyzed.

Main Results

CIS administration significantly reduced testosterone, LH, and FSH levels, and testicular enzyme activities.
CIS induced elevated oxidative stress, inflammation, and apoptosis markers, with miR-155 overexpression and low miR-34c expression.
Histological examination revealed marked testicular degeneration in the CIS group.
NAC and/or LA administration improved testicular function, histopathology, and immunohistochemical profiles.
Combined NAC and LA treatment showed a more significant protective effect than either agent alone.
NAC and LA modulated the expression of miR-155 and miR-34c.

Conclusions

NAC and LA demonstrate significant ameliorative effects against cisplatin-induced testicular toxicity and dysfunction.
These protective effects are mediated through the regulation of antioxidant, anti-inflammatory, and antiapoptotic pathways.
Modulation of miR-155 and miR-34c expression by NAC and LA contributes to their protective mechanisms.
Combined NAC and LA therapy offers enhanced protection against chemotherapy-induced testicular damage.

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