Aims: Paclitaxel (Pax) is a chemotherapeutic drug from the taxane family that is used in the treatment of human cancer, including ovarian, breast, and non-small cell lung carcinoma. Chrysin (CR) has antioxidant, anti-inflammatory, anti-apoptotic, anti-diabetic, and anti-carcinogenic properties, as well as hepatoprotective and renoprotective activities. In the present study, we evaluated the protective effect of CR against Pax-induced hepatorenal toxicity on inflammation, apoptosis, antioxidant levels, oxidative DNA damage, and histopathology in rats.
Material and methods: Thirty-five male Sprague-Dawley rats were divided into five groups (n = 7): Group I (normal control), Group II (CR alone at a dose of 50 mg/kg), Group III (Pax at a dose of 2 mg/kg), Group IV (Pax+CR 25), and Group V (Pax+CR 50). The expressions of apoptotic (Bax and Bcl-2) and antioxidant genes (SOD1, CAT, GPx3, and GST) were evaluated using RT-PCR from paraffin sections. Caspase 3, KIM-1, NF-kB, COX-2, and 8-OHdG were also determined by immunohistochemical examination.
Key findings: The results revealed that Pax exposure caused hepatic and renal damage in rats, which was indicated by a significant elevation of caspase 3, Bax, KIM-1, NF-kB, COX-2, and 8-OHdG. However, there was a marked downregulation in the expressions of the Bcl-2, SOD1, CAT, GPx3, and GST genes. In contrast, rats given CR in combination showed better gene expression, histological structure, and immunohistochemical staining results.
Significance: Consequently, CR exhibited the ability to reduce oxidative DNA damage, exert anti-apoptotic and anti-inflammatory properties, and mitigate the toxic effects of Pax-induced hepatorenal toxicity.
Keywords: Antioxidant; Apoptosis; Chemotherapy; Chrysin; Inflammation; Paclitaxel.
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