One of the adverse effects of cisplatin (CIS) treatment is its reproductive toxicity, which limits its clinical use in male patients. The aim of our study was to investigate the potential protective effects and mechanisms of chlorogenic acid (CHA), a well-known antioxidant and anti-inflammatory polyphenol, in a CIS-induced testicular toxicity model. To this end we divided 30 Sprague-Dawley rats into five groups: control and four groups receiving either CHA alone (3 mg/kg), CIS alone (5 mg/kg), or their weaker and stronger combinations: CIS+CHA (1.5 mg/kg) and CIS+CHA (3 mg/kg), respectively. In the combination groups the rats first received a single 5 mg/kg dose of CIS, followed by either 1.5 or 3 mg/kg of CHA administered intraperitoneally for three consecutive days. Testicular tissues were harvested on the fifth day of the experiment. The level of testicular oxidative stress and inflammation induced by CIS and the histopathological changes observed were restored to normal following treatment with both doses of CHA. Furthermore, treatment with CHA led to the regeneration of Nrf2 and HO-1 levels, which had been suppressed by CIS. Consequently, the levels of endoplasmic reticulum stress and apoptosis were reduced. These findings indicate that CHA may counter the reproductive toxicity of CIS and may therefore serve as its add-on in cancer therapy.
Jedan od štetnih učinaka cisplatina je njegova reproduktivna toksičnost, koja ograničava kliničku primjenu ovog antitumorskog lijeka u muškaraca. Cilj našeg istraživanja bio je ispitati moguće zaštitne učinke i mehanizme djelovanja klorogenske kiseline, poznatog antioksidansa i protuupalnog polifenola, na modelu toksičnosti za testise prouzročene cisplatinom. U tu smo svrhu podijelili 30 štakora soja Sprague-Dawley u pet skupina: kontrolnu skupinu i četiri skupine koje su primale samo klorogensku kiselinu (3 mg/kg), samo cisplatin (5 mg/kg) ili njihovu kombinaciju s nižom ili višom dozom klorogenske kiseline (1,5 odnosno 3 mg/kg). U kombiniranim skupinama štakori su prvo primili jednokratnu dozu cisplatina (5 mg/kg), a zatim su tri uzastopna dana intraperitonealno primali klorogensku kiselinu u nižoj odnosno višoj dozi. Tkivo testisa prikupljeno je petog dana pokusa. Razina oksidacijskoga stresa i upale u testisima izazvane cisplatinom te promjene u histološkoj građi vraćene su na normalne vrijednosti nakon primjene obiju doza klorogenske kiseline. Nadalje, primjena klorogenske kiseline dovela je do obnove razina Nrf2 i HO-1 nakon prvotne inhibicije cisplatinom. Posljedično su se smanjile razine stresa endoplazmatskoga retikuluma i apoptoze. Ovi rezultati upućuju na to da klorogenska kiselina može ublažiti reproduktivnu toksičnost cisplatina te stoga poslužiti kao dodatak u liječenju raka.
Keywords: HO-1; Nrf2; apoptosis; apoptoza; endoplasmic reticulum stress; inflammation; oksidacijski stres; oxidative stress; stres endoplazmatskoga retikuluma; upala.
© 2025 Elif Ayazoğlu Demir et al., published by Sciendo.