Abstract:Background Naringin as a bioflavanone glycoside is abundant in citrus fruits, which since ancient times have been utilized as natural herbal treatments in traditional medicine. Naringin has potent antioxidant effect that may mitigate oxidative stress mediated cardiovascular and renal dysfunctions in mammalian systems. Objective To explore probable modulatory actions of naringin on fipronil-induced cardio-renal dysfunctions. Methods Twenty-four Wistar rats weighing 140 ± 3.0 g were divided into four groups including normal control (saline), 10 mg/kg Fipronil (FIP), FIP+100 mg/kg naringin, and 100 mg/kg naringin. Administration of naringin and fipronil was by oral gavage for 28 consecutive days. Urinalysis, blood pressure monitoring, biochemical assays, histology, and immunohistochemical evaluations were performed. Results Naringin significantly (P < 0.001) lessened blood pressure parameters, oxidative stress markers but significantly (P < 0.001) heightened the systemic antioxidants. Likewise, naringin prevented fipronil-induced histopathological lesions such as congestion and cellular infiltration in cardiac and renal tissues. Moreover, naringin attenuated the immunohistochemical expression of troponin 1 and matrix metalloperoxidase-2 in cardiac tissues, but heightened angiotensin converting enzyme 2 expression in contrast to that of fipronil group. Conclusion The observation in this study shows potent attenuation of fipronil-induced toxicity by naringin, through inhibiting processes related to oxidation and inflammation.