Polyphenolic‑rich fraction of Pithecellobium dulce attenuates methotrexate‑induced oxidative stress and associated tissue injury by regulating the TNF‑α, IL‑1β and IL‑6 pro‑inflammatory cytokines

Abstract

The fruits of <em>Pithecellobium dulce</em> (P. dulce) are edible, and have been consumed in Asian countries. They are considered a dense source of proteins, fats, carbohydrates and vitamins. The present study aimed to explore the antioxidant (<em>in vitro</em> and <em>in vivo</em>) effects of the fruit extract of <em>P. dulce</em> (FPD) against methotrexate (MTX)‑induced hepatic and renal toxicities in a BALB/c mouse model. A preliminary qualitative analysis of FPD was carried out following standard procedures. The <em>in vitro</em> antioxidant efficacy of FPD was evaluated by different free radical scavenging assays. In order to further validate the protective effects of FPD, an expansive <em>in vivo</em> experimental strategy was developed. Oxidative stress was induced in mice by an intraperitoneal (i.p) injection of MTX (20 mg/kg body weight). The protective effects of FPD against MTX‑induced oxidative stress were evaluated following the oral administration of FPD at 40 mg/kg body weight for 10 consecutive days. Preliminary qualitative analysis of FPD revealed the presence of several active phyto‑components. The <em>in vitro</em> antioxidant efficacy of FPD was evaluated, and a concentration‑dependent increment in antioxidant activity was observed. These data from the cell free system represent a clear approximation of the antioxidant status of potential bioactive constituents. The administration of FPD significantly reduced MTX‑induced serum hepatic and renal toxicity marker enzymes. The co‑administration of FPD also reduced the levels of tissue oxidative stress markers and enhanced the antioxidant status in the liver, kidneys and lungs of mice compared with the MTX alone group. FPD also reversed MTX‑induced pancytopenia. Furthermore, the protective effects of FPD were confirmed by tissue histopathological analysis. Additionally, treatment with FPD markedly reduced the MTX‑induced increase in the levels of serum pro‑inflammatory cytokines, such as TNF‑α, IL‑1β and IL‑6. On the whole, the findings of the present study strongly ascertain the antioxidant efficacy of FPD and its role in mitigating MTX‑induced tissue injury.