Key result
Tadalafil pretreatment significantly ameliorated doxorubicin-induced hepatorenal toxicity and biochemical alterations in Wistar rats (p<0.05 to p<0.0001).
Why the study?
Clinical application of doxorubicin is limited by off-target hepatorenal toxicity, and tadalafil has shown potential in reducing oxidative stress.
Does tadalafil pretreatment reduce doxorubicin-induced hepatorenal toxicity in Wistar rats?
Does tadalafil pretreatment reduce doxorubicin-induced hepatorenal toxicity in Wistar rats?
p-value: p=<0.05
Tadalafil pretreatment effectively attenuates doxorubicin-induced hepatorenal toxicity in a rat model through antioxidant and anti-inflammatory mechanisms.
Tadalafil may mitigate doxorubicin hepatorenal toxicity in rats; leaves open translation to patients.
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.
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Adeneye et al. (2024) studied Doxorubicin-induced hepatorenal toxicity (n=48). Tadalafil vs. Sterile water or silymarin was evaluated on Hepatorenal toxicity (serum K+, urea, creatinine, and antioxidant enzyme activity) (p=<0.05). Tadalafil pretreatment significantly ameliorated doxorubicin-induced hepatorenal toxicity and biochemical alterations in Wistar rats (p<0.05 to p<0.0001).
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