Pioglitazone improves tamoxifen-induced renal injury in rat model through modulating oxidative stress, inflammation, and apoptosis signaling.

Abstract

One prevalent chemotherapeutic medication used to treat breast cancer is tamoxifen (TAM), and several off-label uses. However, when used as an antineoplastic drug in clinical settings, it causes harmful cellular effects such as renal damage. The mechanisms underlying TAM-induced kidney injury primarily involve oxidative stress and inflammatory pathways. Pioglitazone (PIO), an agonist of peroxisome proliferator-activated receptor-gamma (PPAR-γ), is a medication primarily indicated for type 2 diabetes mellitus. Beyond its hypoglycemic actions, PIO exhibits potent anti-inflammatory and antioxidant effects, which have been documented in various tissues. Hence, this study investigates the potential protective effects of PIO on TAM-induced renal impairment, revealing their possible protective mechanisms. The rats were orally administered doses of PIO (10 mg/kg) and TAM (45 mg/kg) over ten days. Renal histopathological changes, kidney function, and biochemical examination are conducted. TAM raised serum creatinine and urea levels, leading to histopathological changes, renal oxidative stress, and elevated expression of NF-κB p65 and proinflammatory cytokines. Conversely, PIO treatment exerted a protective effect and attenuated TAM-induced nephrotoxicity. Significantly, malondialdehyde (MDA) and proinflammatory markers were reduced while enhancing renal antioxidant activity. Furthermore, renal Nrf2, HO-1, Bcl-2 expression while lowering NF-κB, KIM-1, Bax and caspase-3 levels. In conclusion, PIO demonstrated significant nephroprotective effects against TAM-induced renal damage by inhibiting apoptosis, reducing inflammation, and counteracting oxidative stress.