Protective effects of Lagerstroemia speciosa against paracetamol-induced renal and testicular toxicity in rats via antioxidant, anti-inflammatory, and anti-apoptotic mechanisms

Introduction: Paracetamol (PCM) is widely used as an analgesic; however, at high doses, it is well recognized for its hepatotoxic effects and is increasingly associated with renal and reproductive damage. Methods: leaf extract (EELS; 500 mg/kg/day, orally for 24 days) was investigated against PCM-induced kidney and testicular injury in male rats, using N-acetyl cysteine (NAC) as a reference treatment. Results: PCM administration led to pronounced impairment in sperm quality and significant disturbances in serum biochemical parameters, reflected by elevated renal function markers, sodium, and phosphorus levels, together with reduced calcium, potassium, and testosterone. These changes were accompanied by clear evidence of oxidative stress, as indicated by increased malondialdehyde and decreased reduced glutathione. Moreover, inflammatory and apoptotic responses were markedly intensified, whereas antioxidant and steroidogenic regulators were suppressed. Histopathological findings further confirmed extensive structural damage in renal and testicular tissues. Notably, treatment with EELS or NAC substantially mitigated these alterations, restoring most parameters toward normal values. Conclusion: Collectively, these findings demonstrate that EELS exerts notable nephroprotective and gonadoprotective effects comparable to NAC, largely through the attenuation of oxidative stress, inflammation, and apoptosis.