Naringin protects against cyclophosphamide-induced hepatotoxicity and nephrotoxicity through modulation of oxidative stress, inflammation, apoptosis, autophagy, and DNA damage.

Environmental Science and Pollution Research International
Cuneyt CaglayanSefa Kucukler

Abstract

Cyclophosphamide (CP) is a common chemotherapeutic agent that is effective against a wide variety of tumors. The associated hepatotoxicity and nephrotoxicity, however, limit its therapeutic use. Naringin (NG) is a natural flavanone glycoside that has pharmacological and therapeutic activities, such as anti-inflammation, anti-apoptotic, and antioxidant properties. Therefore, the present study was undertaken to evaluate the protective effect of NG against CP-induced hepatotoxicity and nephrotoxicity in rats. Rats were pre-treated with NG (50 and 100 mg/kg b.w.) for 7 days before administering a single dose of CP (200 mg/kg b.w.) on the seventh day. CP-induced hepatotoxicity and nephrotoxicity were associated with an increase in serum toxicity markers and a decrease in antioxidant enzyme activities. CP also induced inflammatory responses by increasing the levels of tumor necrosis factor-α (TNF-α), nuclear factor kappa B (NF-κB), interleukin-6 (IL-6), and interleukin-1β (IL-1β), and activities of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2). Moreover, it activated the apoptotic and autophagic pathway by increasing cysteine aspartate-specific protease-3 (caspase-3) expression and light chain 3B (LC3B) level an...Continue Reading

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