Work

Tadalafil pretreatment attenuates doxorubicin-induced hepatorenal toxicity by modulating oxidative stress and inflammation in Wistar rats

Year: 2024

Type: article

Abstract: Doxorubicin (DOX) is a widely used anticancer agent, but its clinical application is limited by significant off-target hepatorenal toxicity. Tadalafil (TAD), a selective phosphodiesterase-5 inhibitor used mainly for erectile dysfunction and pulmonary arterial hypertension, has shown potential in reducing oxidative stress. This study investigated TAD's chemoprotective effects and underlying mechanisms in DOX-induced hepatorenal toxicity in rats over 12 days. Eight groups of six rats each were orally pretreated with sterile water, silymarin (SIL), or TAD one hour before receiving intraperitoneal injections of 2.5 mg/kg DOX. On the 13th day, the rats were humanely sacrificed under inhaled halothane anesthesia, and serum was collected for hepatic and renal function tests, while liver and kidney tissues were analyzed for antioxidant enzyme activity, pro-inflammatory cytokines assay, and histopathological evaluation. DOX successfully induced hepatorenal toxicity, evidenced by significant increases (p<0.001, p<0.0001) in serum K + , urea, and creatinine levels, along with decreases in HCO 3 - , TCa 2+ , and Cl - . Tissue analysis showed reduced SOD, CAT, GST, and GPx activities, with elevated MDA and GSH levels. TAD pretreatment significantly ameliorated these biochemical alterations (p<0.05, p<0.001, p<0.0001), suggesting its potential as an effective chemoprophylactic adjuvant in the development of DOX-induced hepatorenal toxicity. • Doxorubicin (DOX) is notorious for causing hepatorenal toxicity as its off-target side effect. • Intraperitoneal injections of 2.5 mg/kg DOX for 12 days resulted in hepatorenal toxicities in the treated rats. • Tadalafil (TAD) pretreatments effectively attenuated and reversed these toxicities via antioxidant and anti-inflammatory mechanisms.

Source: Toxicology Reports

DOI: 10.1016/j.toxrep.2024.101737

Authors: Adejuwon Adewale Adeneye, Fidaraoluwa Esther Babatope, Ademilayo Eunice Adesiji-Adelekan, Olufunke Esan Olorundare, Ikechukwu Innocent Okoye

Institutions: Lagos State University, University of Ilorin

Language: English

Topic: Chemotherapy-induced organ toxicity mitigation

Subfield: Pathology and Forensic Medicine

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $2,230