β-Sitosterol Prevents Lipid Peroxidation and Improves Antioxidant Status and Histoarchitecture in Rats with 1,2-Dimethylhydrazine-Induced Colon Cancer

Abstract

Oxidative stress has become widely viewed as an underlying condition in diseases such as ischemia/reperfusion disorders, central nervous system disorders, cardiovascular disease, cancer, diabetes, etc. The role that antioxidants play in the process of carcinogenesis has recently gained considerable attention. β-Sitosterol, a naturally occurring sterol molecule, is a relatively mild to moderate antioxidant and exerts beneficial effects in vitro by decreasing the level of reactive oxygen species. The present study evaluated the antioxidant potential of β-sitosterol in 1,2-dimethylhydrazine (DMH)-induced colon carcinogenesis. The enzymatic and nonenzymatic antioxidants and lipid peroxides in colonic and hepatic tissues were evaluated. Generation of reactive oxygen species, beyond the body's endogenous antioxidant capacity, causes a severe imbalance of cellular antioxidant defense mechanisms. Elevated levels of liver lipid peroxides by DMH induction were effectively decreased by β-sitosterol supplementation. β-Sitosterol also exhibited a protective action against DMH-induced depletion of antioxidants such as catalase, superoxide dismutase, glutathione peroxidase, glutathione reductase, glutathione S-transferase, and reduced glutathione in colonic and hepatic tissues of experimental animals. Supplementation with β-sitosterol restored the levels of nonenzymatic antioxidants (vitamin C, vitamin E, and glutathione). Histopathological alterations in DMH-induced animals were restored to near normal in rats treated with β-sitosterol. Thus, β-sitosterol by virtue of its antioxidant potential may be used as an effective agent to reduce DMH-induced oxidative stress in Wistar rats and may be an effective chemopreventive drug for colon carcinogenesis.

Amelioration of 1,2 Dimethylhydrazine (DMH) Induced Colon Oxidative Stress, Inflammation and Tumor Promotion Response by Tannic Acid in Wistar Rats

“…Protective efficacy of tannic acid in DMH induced oxidative stress can be possibly due to its ability to induce antioxidant enzymes like GR, GST.GPX etc. as previously reported from our laboratory and by others too (Tsujiiet al, 1998;Gülçin et al, 2010;Ahmad and Sultana, 2012;Baskar et al, 2012).…”

Cytotoxic Steroids from the Bark of Aglaia argentea (Meliaceae)

“…They include β-sitosterol, campesterol, stigmasterol, and cycloartenol (Ostlund et al, 2002). Sterols, especially β-sitosterol, have been reported to have the following activities or effects: anti-inflammatory (Prieto et al, 2006), inducing apoptosis (Ju et al, 2004;Park et al, 2007;Chai et al, 2008), chemoprotective or chemopreventive (Ovesna et al, 2004), hypocholesterolemic (Zak et al, 1990), angiongenic (Moon et al, 1999), anti-diabetic (Jamaluddin et al, 1994;Gupta et al, 2011;Radika et al, 2013), and anti-oxidant (Vivancos and Moreno, 2005;Baskar et al, 2012).…”

Anti-proliferative effect of main dietary phytosterols and β-cryptoxanthin alone or combined in human colon cancer Caco-2 cells through cytosolic Ca+2 – and oxidative stress-induced apoptosis

“…These compounds are well known for their effects on cholesterol blood levels (Wong, 2014); however, research into their potential role in mitigating cancer risk, and specifically colon cancer, has received comparably little attention (Bradford & Awad, 2010;Grattan, 2013). It has been reported that β-sitosterol, the prevalent Ps in the diet, has antiproliferative effects in rat models of colon cancer (Awad, Tagle-Hernandez, Fink, & Mendel, 1997;Baskar et al, 2012;Baskar, Ignacimuthu, Paulraj, & Al Numair, 2010;Raitch, Cohen, Faqzzani, Sarwal, & Takahashi, 1980) and in the colon cancer cell lines HT-29, HCT116 and Colo 320, within the range of physiological plasma concentrations (4-70 µM) (Awad, Chen, Fink, & Hennessey, 1996;Awad & Fink, 2000;Choi et al, 2003;Jayaprakasha, Jadegoud, Nagana Gowda, & Patil, 2010;Montserrat-de la Paz, Fernández-Arche, Bermúdez, & García-Giménez, 2015). In other cases, inhibition of colon cancer cell growth (Caco-2 cells) has been observed with pharmacological levels of β-sitosterol and campesterol (≥100 µM) (Daly, Aherne, O'Connor, & O'Brien, 2009).…”