Silymarin Protection against Major Reactive Oxygen Species Released by Environmental Toxins: Exogenous H₂O₂ Exposure in Erythrocytes

Abstract

Silymarin is a polyphenolic plant flavonoid (a mixture of flavonoid isomers such as silibinin, isosilibinin, silidianin and silichristin) derived from Silymarin marianum that has anti-inflammatory, hepatoprotective and anticarcinogenic effects. Our earlier studies have shown that silymarin plays a protective role against the oxidative damage induced by environmental contaminants like benzo(a)pyrene in erythrocyte haemolysates. During the detoxification of these environmental contaminants, the major reactive oxygen species generated is hydrogen peroxide (H 2 O 2 ). Because H 2 O 2 can easily penetrate into the cell and cause damage to biomolecules, the protective role of silymarin was further assessed against this cytotoxic agent in vitro in erythrocyte haemolysates. The protective effect was monitored by assessing the levels of the antioxidant enzymes superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase, glutathione-s -transferase, glutathione peroxidase and malondialdehyde (LPO) in three groups: vehicle control, H 2 O 2 -exposed groups and drug co-incubation group (H 2 O 2 + silymarin). The protective effect of silymarin on the non-enzymic antioxidant glutathione and haemolysis, methaemoglobin content and protein carbonyl content were also assessed. It was observed that the activities of antioxidant enzymes and glutathione were reduced and the malondialdehyde levels were elevated after H 2 O 2 exposure. There were also alterations in haemolysis, methaemoglobin content and protein carbonyl content, whereas after the administration of silymarin, the antioxidant enzyme activities reversed to near normal with reduced malondialdehyde content and normalized haemolysis, methaemoglobin content and protein carbonyl content. The results suggest that silymarin possesses substantial protective effect and free radical scavenging mechanism against exogenous H 2 O 2 -induced oxidative stress damages, hence, can be used as a protective drug against toxicity induced by environmental contaminants.

Multitargeted therapy of cancer by silymarin

“…Kiruthiga et al [46] have shown that administration of silymarin increases the activities of antioxidant enzymes like superoxide dismutase (SOD), catalase, glutathione peroxidase (GPx), glutathione reductase (GR) and glutathione-s-transferase (GST) together with a decrease in the levels of malondialdehyde (MDA), a marker for lipid peroxidation, in erythrocytes exposed to H 2 O 2 . Silymarin application extensively reduces GSH depletion and ROS production as well as lipid peroxidation in UVA irradiation-induced damage in human keratinocytes.…”

Providing the plant extract silymarin to lactating sows: effects on litter performance and oxidative stress in sows

“…Indeed, silymarin decreased the liver protein carbonyl content, without affecting mitochondrial oxidative status and gene expression of the principal cellular antioxidants, and reduced the accumulation of circulating protein carbonyls. Similar actions of silymarin on protein carbonyls were also observed in rodents (Kiruthiga et al, 2007;Turgut et al, 2008), and there are indications that a combination of silymarin and lycopene has a protective effect against lipoperoxidation in periparturient cows (Garavaglia et al, 2015). The potential of silymarin to alleviate systemic oxidative conditions during lactation was never previously investigated in sows.…”

Silymarin regulates HIF-1α and iNOS expression in the brain and gills of hypoxic-reoxygenated rainbow trout Oncorhynchus mykiss

“…Therefore, SMN acts both transcriptionally and post-transcriptionally, as we showed in the present study. The antioxidant effect of SMN is mainly attributable to its antiradical and ROS scavenging capabilities (Kiruthiga et al 2007, Shaker et al 2010. Moreover, other mechanisms, such as increasing the pro-oxidant-reduced mitochondrial membrane potential and inhibition of the sepsis-elevated cytokines (IL-1β and PGE 2 ) production, can also explain the SMN-induced antioxidant effects (Kang et al 2004).…”