Abstract
The present work was designed to assess the efficacy of Silybum marianum total extract (STE), silymarin (Sm), and silibinin (Sb) against experimentally induced renal carcinogenesis in male Wistar rats and their roles in regulating oxidative stress, inflammation, apoptosis, and carcinogenesis. The diethylnitrosamine (DEN)/2-acetylaminofluorene (AAF)/carbon tetrachloride (CCl4)-administered rats were orally treated with STE (200 mg/kg b.w.), Sm (150 mg/kg b.w.), and Sb (5 mg/kg b.w.) every other day either from the 1st week or from the 16th week of carcinogen administration to the end of 25th week. The treatments with STE, Sm, and Sb attenuated markers of toxicity in serum, decreased kidney lipid peroxidation (LPO), and significantly reinforced the renal antioxidant armory. The biochemical results were further confirmed by the histopathological alterations. The treatments also led to suppression of proinflammatory mediators such as NF-κβ, p65, Iκβα, and IL-6 in association with inhibition of the PI3K/Akt pathway. Furthermore, they activated the expressions of PPARs, Nrf2, and IL-4 in addition to downregulation of apoptotic proteins p53 and caspase-3 and upregulation of antiapoptotic mediator Bcl-2. The obtained data supply potent proof for the efficacy of STE, Sm, and Sb to counteract renal carcinogenesis via alteration of varied molecular pathways.
Highlights
Kidney cancer is one of the most common malignant tumors of the genitourinary system, and it is among the cancer types that have the highest growth rate in all age and racial groups worldwide [1]
Antibodies for p-PI3K and β-actin were obtained from Santa Cruz Biotechnology (USA). t-PI3K, t-Akt, p-Akt, t-p65, p-p65, t-IκBα, and p-IκBα antibodies were purchased from Cell Signaling Technology, Inc. (USA)
The concentrations of urea, creatinine, and uric acid were significantly (P < 0:001) increased in the serum of DEN/AAF/CCl4-administered rats comparing to the normal control group
Summary
Kidney cancer is one of the most common malignant tumors of the genitourinary system, and it is among the cancer types that have the highest growth rate in all age and racial groups worldwide [1]. Several risk factors are claimed to predispose to kidney cancer involving chronic renal disease, hereditary syndrome, hypertension, obesity, cigarette smoking, long-term dialysis, genetic susceptibility, and maybe the result of exposure to different environmental toxicants [4]. Oxidative stress is defined as an imbalance between the generation of reactive oxygen species (ROS) and the biological system’s ability to counteract the effects of reactive free. High amounts of ROS can compromise the antioxidant defense system resulting in DNA, protein, and lipid damage [6]. The diminished effectiveness of the antioxidant defense system may aggravate oxidative damage [7]. Oxidative stress is a major cause of various renal diseases that stimulates progression from acute to chronic damage and the development of kidney cancer [10]
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