Introduction: Methotrexate (MTX) is a commonly used chemotherapeutic and immunosuppressant drug. Nevertheless, due to its numerous side effects, clinical use is restricted. Lactoferrin (Lf) a natural milk glycoprotein with anti-viral, anti-inflammatory, and antioxidant characteristics are among the various pharmacological effects.
Aim of the Study: Assessment of the reno-protective potential of Lf in experimental MTX-induced nephrotoxicity and renal damage.
Material and Methods: A total of twenty-eight adult male albino rats were allocated into four groups: control group, Lf treated group received Lf (300mg/kg/day) orally for 2 weeks; MTX treated group received MTX by intraperitoneal route (20mg/kg) once; and Lf +MTX treated group. Kidney functions, redox status, interleukin (IL)-1β level and tumor necrosis factor (TNF)-α expression were assessed. Moreover, histological characteristics were assessed by light and electron microscopic study.
Results: MTX nephrotoxicity was evidenced by significantly impaired renal functions, increased renal malodialdehyde (MDA) level, IL-1β level, and TNF-α protein expression along with significant decreases in renal GSH and antioxidant enzymes activities. The biochemical results were confirmed by histopathology results that showed disturbed architecture, glomerular atrophy and congestion, damaged tubular cells, interstitial bleeding and inflammatory infiltration with significant increase in collagen fibers and decreased PAS staining. Ultrastructure study revealed; degenerated mitochondria, cytoplasmic vacuoles, and basement membrane damage in renal tubules. Additionally, renal filtration barrier was disrupted. Meanwhile, Lf treatment improved renal function, redox state, inflammation, histology and ultrastructural characteristics.
Conclusion: Lf has the potential to protect the kidneys against MTX-induced nephrotoxicity and cytotoxicity. Results herein suggested that Lf, as an adjuvant therapy, may be valuable in preventing the occurrence of renal damage in patients on MTX or other reno-toxic drugs.