Hepatorenoprotective effects of Lepidium draba L. extracts against cyclophosphamide-induced oxidative injuries in rats via reducing apoptosis and inflammation

Abstract

Objective: To investigate the protective effects of Lepidium draba L. (L. draba) on cyclophosphamide (CP)-induced hepatotoxicity and nephrotoxicity in rats.

Methods: A total of 36 rats were divided into six groups as follows: the sham control group, the CP group (CP 100 mg/kg i.p. on days 1, 7, 14, 21, 28, and 35), the CP groups treated with L. draba extract (100, 200 and 400 mg/kg of L. draba extract for 28 d), and the L. draba extract alone group (400 mg/kg of L. draba extract for 28 d). Serum parameters of renal and hepatic function, as well as pro-inflammatory and anti-inflammatory cytokines associated with liver and kidney damage were measured. Moreover, Bax, Bcl-2, and caspase-3 gene expression and histopathological changes were assessed.

Results: L. draba extract alleviated CP-induced hepatotoxicity and nephrotoxicity by decreasing nitric oxide, TBARS, IL-6, TNF-α, and IL-Ιβ levels, as well as increasing superoxide dismutase, catalase and glutathione peroxidase activities, and FRAP, MIF, and TGF-β levels. In addition, the extract downregulated the expression of pro-apoptotic genes (Bax and caspase-3) and mitigated the destruction of glomeruli and renal tubules as well as the degeneration of hepatocytes.

Conclusions: L. draba extract can protect hepatic and renal structure and function against CP-induced toxicities, and may be used as a therapeutic agent for CP-induced hepatotoxicity and nephrotoxicity.

Keywords

Lepidium draba / Cyclophosphamide / Oxidative stress / Antioxidant / Apoptosis / Hepatotoxicity / Nephrotoxicity