Effects of Lycopene, Indole-3-Carbinol, and Luteolin on Nitric Oxide Production and iNOS Expression are Organ-Specific in Rats

Abstract

Natural compounds are known to modify NO content in tissues; however, the biological activity of polyphenol-rich food often does not correspond to the effects of individual polyphenols on NO synthase activity. The aim of this study was to see how natural compounds luteolin, indole-3-carbinol, and lycopene modify NO production in rat tissues and change the expression of the iNOS gene and protein. Indole-3-carbinol produced multiple effects on the NO level; it signifi cantly decreased NO concentration in blood, lungs, and skeletal muscles and increased it in the liver. Indole-3-carbinol enhanced lipopolyssaccharide (LPS)-induced NO production in all rat organs. It decreased iNOS gene expression in the brain cortex of animals that did not receive LPS and up-regulated it in the LPS-treated animals. Lycopene increased the iNOS gene transcription rate in the brain cortex of LPS-treated animals. Luteolin did not modify NO production in any organ of LPS-untreated rats, nor did it affect gene expression in the liver. In the brain it slightly decreased iNOS gene expression. Luteolin decreased NO production in the blood of LPS-treated animals and the number of iNOS-positive cells in these animals. Our results suggest that changes in tissue NO levels caused by natural compounds cannot be predicted from their effect on NOS expression or activity obtained in model systems. This stresses the importance of direct measurements of NO and NOS expression in animal tissues. Toksikol 2010;61:275-285 Natural biologically active compounds of plant origin such as flavonoids are widely used as dietary supplements with detoxicating effects. The detoxicating effect of many plant-derived compounds is based on their antioxidant, anti-mutagenic, and anti-carcinogenic effects (1, 2). These substances are also known to infl uence the enzymatic production of nitric oxide (NO) and its stability. (3). This underlines the signifi cance of the uptake of fl avonoid and other natural compound for the defence of cardiovascular, immune, and nervous systems against toxins. However, the biological activity of polyphenol-rich food does not correspond to the effects of individual compounds on NO synthase activity. For example, red wine is known as a vasodilator (4) and is rich in quercetin. Purifi ed quercetin inhibits inducible nitric oxide synthase (iNOS) gene expression (3, 5), destabilises endothelial NOS (eNOS) mRNA (6), KEY WORDS: ESR spectroscopy, inducible nitric oxide synthase, natural compounds, NO Rostoka E, et al. EFFECTS OF NATURAL COMPOUNDS ON NO AND iNOSArh Hig Rada

Effects of Lycopene Alone or Combined with Melatonin on Methotrexate-Induced Nephrotoxicity in Rats

“…Several reports clearly indicated that the Lyc which possesses many conjugated double bonds is known with its high antioxidant activity and free radical scavenging capacity (Cohen, 2002;Jonker et al, 2003;Michael McClain and Bausch, 2003;Tapiero et al, 2004;Velmurugan et al, 2004;Rostoka 2010). Lyc treatment, either before or after cisplatin administration, provided a significant protection against cisplatin-induced nephrotoxicity (Atessahin et al, 2005).…”

Indole-3-carbinol protects against cisplatin-induced acute nephrotoxicity: role of calcitonin gene-related peptide and insulin-like growth factor-1

“…In fact, indole-3-carbinol had been found to reduce the expression of pro-inflammatory cytokines such as IL-1β, IL-6, TNF-α and NF-kB 18 19 21 . Also, the expression of cyclooxygenase-2, lipoxygenase and inducible nitric oxide synthase enzymes was significantly reduced by indole-3-carbinol administration 22 23 . Moreover, indole-3-carbinol was shown to possess chemopreventive 24 as well as anti-tumor activities 25 26 via interference with a variety of signal transduction pathways involved in cell survival 23 .…”

Lycopene and Caffeic Acid Phenethyl Ester Affect Caspase-3 Activity, but Do Not Alter the NO Pathway in Lung Tissue Damage Induced by Cisplatin

“…These results might seem inconsistent since CAPE was previously found to inhibit inducible NOS activity; however, it is also found that CAPE can cause an increase in the endothelial NOS activity which increases the NO production [17]. Also, lack of activity of LCP on CP-induced increase in NO production is not unexpected since this antioxidant previously failed to prevent lipopolysaccharide-induced increase in rat lung iNOS and NO activity/concentrations [18]. The absence of any notable action of LCP and CAPE on CP-induced increase in NO production might be related to the organ-specific action of 2 tested antioxidants, which has been reported for different natural compounds [18].…”