Abstract
BackgroundSide effects of cisplatin (CIS) such as testicular toxicity restrict its clinical use. Instead, evidence indicates that crocin (CR) has synergistic anti-cancer potential with CIS and exhibited beneficial effects on CIS-induced hepatorenal damage. The aim of this study was to investigate the protective potential of CR against CIS-induced testicular toxicity in rats.MethodsFifty adult male Wistar rats randomly assigned to five equal groups including control, CIS, and CIS plus CR at doses of 6.25 mg/kg (CIS + CR6.25), 25 mg/kg (CIS + CR25), and 100 mg/kg (CIS + CR100). CIS and CIS + CR groups received a single intraperitoneally (i.p.) injection of CIS (7 mg/kg). CR (6.25–100 mg/kg i.p.) injections were started three days before the CIS injection and continued once a day for up to 13 days. On the 14th day, all animals were sacrificed and their blood samples and testes were removed for biochemical and histological analyses.ResultsCompared to the control group, CIS significantly decreased relative testis weight (0.28 vs. 0.39, p < 0.001), testosterone level (0.3 vs. 2.31 ng/mL, p < 0.001), germinal layer area (25,886 vs. 35,320 µm2, p < 0.001), superoxide dismutase (SOD) (0.9 vs.1.73 U/mg, p < 0.001) and increased testicular lipid peroxidation (3.05 vs. 15.35 nmol/mg, p < 0.001). CR at 25 mg/kg ameliorated testicular lipid peroxidation and enhanced SOD activity compared to CIS group (p < 0.05). Besides, CR treatment at the maximum dose (100 mg/kg) resulted in reversing CIS effects on testis weight, testosterone level, SOD, lipid peroxidation, and germinal layer area.ConclusionsThese findings demonstrated that CR co-treatment could prevent CIS-induced testicular toxicity in rats.
Highlights
Side effects of cisplatin (CIS) such as testicular toxicity restrict its clinical use
Previous studies revealed that several natural products such as eugenol, curcumin and arjunolic acid could limit CIS-induced testicular damage by reducing oxidative stress and anti-inflammatory properties [10,11,12,13,14,15]
The CIStreated animals exhibited lower body-weight, absolute and relative testicular weights compared to the control group (p < 0.001 all)
Summary
Side effects of cisplatin (CIS) such as testicular toxicity restrict its clinical use. Despite its promising anti-cancer potential, CIS can adversely affect liver and kidney functions and induce testicular toxicity [1,2,3,4,5]. Several studies found that CIS causes severe testicular damage through impairment of Leydig cell function (inhibiting testosterone production) and induction of germ cell apoptosis. Previous studies revealed that several natural products such as eugenol, curcumin and arjunolic acid could limit CIS-induced testicular damage by reducing oxidative stress and anti-inflammatory properties [10,11,12,13,14,15]. CIS can be used singly or in combination therapy for induction and neoadjuvant therapy in the clinic. It makes CIS a suitable candidate for the combination therapy formula [18]
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