Mitigative potential of rhoifolin against cisplatin prompted testicular toxicity: biochemical, spermatogenic and histological based analysis

Faria Saher; Muhammad Umar Ijaz; Ali Hamza; Qurat Ul Ain; Muhammad Faisal Hayat; Tayyaba Afsar; Ali Almajwal; Huma Shafique; Suhail Razak

doi:10.1093/toxres/tfad073

Mitigative potential of rhoifolin against cisplatin prompted testicular toxicity: biochemical, spermatogenic and histological based analysis

Toxicol Res (Camb). 2023 Aug 26;12(5):814-823. doi: 10.1093/toxres/tfad073. eCollection 2023 Oct.

Authors

Faria Saher¹, Muhammad Umar Ijaz¹, Ali Hamza¹, Qurat Ul Ain², Muhammad Faisal Hayat¹, Tayyaba Afsar³, Ali Almajwal³, Huma Shafique⁴, Suhail Razak³

Affiliations

¹ Department of Zoology, Wildlife and Fisheries, University of Agriculture, Faisalabad 38040, Pakistan.
² Department of Zoology, Government College Women University, Sialkot 51040, Pakistan.
³ Department of Community Health Sciences, College of Applied Medical Sciences, 11433, King Saud University, Riyadh, Saudi Arabia.
⁴ Institute of Cellular Medicine, Newcastle University Medical School, Newcastle University, Newcastle upon Tyne, NE1 7RU, United Kingdom.

PMID: 37915485
PMCID: PMC10615821 (available on 2024-08-26)
DOI: 10.1093/toxres/tfad073

Abstract

Rhoifolin (ROF) is a naturally occurring flavonoid compound with diverse pharmacological and therapeutic benefits. The current investigation was designed to evaluate the curative potential of Rhoifolin (ROF) against Cisplatin (CP) induced testicular damage. Mature male albino rats (n = 48) were randomly distributed into 4 equal groups: control, CP (10 mg/kg), CP + ROF (10 mg/kg + 20 mg/kg) and ROF (20 mg/kg) supplemented group. Following 56 days of the trial, biochemical, inflammatory markers, spermatogenic, steroidogenic, hormonal, apoptotic, anti-apoptotic, and histopathological parameters were evaluated. The exposure to CP markedly (p < 0.05) lowered the activities of anti-oxidant enzymes, glutathione reductase (GSR), catalase (CAT), and glutathione peroxidase (GPx) as well as superoxide dismutase (SOD) in testicular tissues of male albino rats. Besides the levels of reactive oxygen species (ROS) and thiobarbituric acid reactive substances (TBARS) were considerably augmented in CP exposed rats. The administration of CP also increased the level of inflammatory cytokines i.e. IL-6, TNF-α, 1L-1β and NF-κβ as well as COX-2 activity. Additionally, a notable (p < 0.05) upsurge was observed in dead sperms count, abnormality in the tail, midpiece as well as head of sperms along with a notable decline in sperm motility in CP treated rats. Moreover, the expressions of steroidogenic enzymes were also lowered in CP administered group. The levels of follicle stimulating hormone (FSH) and plasma testosterone as well as luteinizing hormone (LH) were decreased in CP treated group. Moreover, the expression of Bax as well as Caspase-3 (apoptotic markers) were increased. On the other hand, Bcl-2 expression (anti-apoptotic marker) was reduced. Furthermore, the histopathological analysis showed that CP considerably (p < 0.05) damaged the testicular tissues. However, the administration of ROF significantly reduced the damaging effects of CP in testicular tissues. The results of our study suggested that ROF can potentially alleviate CP-induced testicular damages due to its androgenic, anti-oxidant and anti-inflammatory as well as anti-apoptotic nature.

Keywords: antioxidant; cisplatin; inflammation; reactive oxygen species; rhoifolin; steroidogenesis.