Silymarin attenuates paraquat‐induced lung injury via Nrf2‐mediated pathway in vivo and in vitro

Abstract

The present study aims to investigate the impacts and mechanisms of silymarin on paraquat (PQ)-induced lung injury in vivo and in vitro. In in vivo experiments, a total of 32 male Sprague-Dawley (SD) rats were randomly divided into four groups. The rats were killed on day 3. Histopathological changes in lung tissue were examined using HE and Masson's trichrome staining. Biomarkers of neutrophil activation, pulmonary oedema, pulmonary fibrosis, lung permeability and oxidative stress were detected. Several proinflammatory mediators and antioxidant related proteins were measured. In in vitro experiments, A549 cells were transfected with Nrf2 special siRNA to investigate the roles of Nrf2. The results show that silymarin administration abated PQ-induced lung histopathologic changes, decreased inflammatory cell infiltration and lung wet weight/dry weight (W/D) ratio, suppressed myeloperoxidase (MPO) activity and nitric oxide (NO)/inducible nitric oxide synthases (iNOS) expression, downregulated hydroxyproline (HYP) levels, reduced total protein concentration and proinflammatory mediator release, and improved oxidative stress (malondialdehyde, MDA; superoxide dismutase, SOD; catalase, CAT; and glutathione peroxidase, GSH-Px) in lung tissue and serum. Meanwhile, treatment with silymarin upregulated the levels of nuclear factor-erythroid-2-related factor 2 (Nrf2), heme oxygenase-1 (HO-1) and NAD(P)H:quinone oxidoreductase-1(NQO1). However, the addition of Nrf2 siRNA reduced the expression of Nrf2-mediated antioxidant protein HO-1 and thus reversed the protective effects of silymarin against oxidative stress and inflammatory response. These results suggest that silymarin may exert protective effects against PQ-induced lung injury. Its mechanisms were associated with the Nrf2-mediated pathway. Therefore, silymarin may be a potential therapeutic drug for lung injury.

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

“…Recent studies revealed that silymarin can scavenge free radicals in the gut, prevent the formation of free radicals by inhibiting specific ROS-producing enzymes and improve the integrity of electron-transport chain of mitochondria in stress conditions (Gabrielova et al, 2015;Surai, 2015;Feng et al, 2016). Silymarin was also shown to maintain an optimal redox balance in cells by activating a range of antioxidant enzymes and non-enzymatic antioxidants via the activation of specific transcription factors (Zhao et al, 2015). Furthermore, it decreases inflammatory responses in the gut and other tissues by inhibiting NF-κB pathways (Gharagozloo et al, 2010).…”

Embelin impact on paraquat‐induced lung injury through suppressing oxidative stress, inflammatory cascade, and MAPK/NF‐κB signaling pathway

“…The mixed group got at 20 mg/kg dose dissolved in saline and two drops of Tween 20 through oral route for 28 progressive days, with a single dose of paraquat at 50 mg/kg through IP route on the 14th day. [ 16,17 ]…”

“…The mixed group got at 20 mg/kg dose dissolved in saline and two drops of Tween 20 through oral route for 28 progressive days, with a single dose of paraquat at 50 mg/kg through IP route on the 14th day. [16,17] On day 28, after medications, through cervical separation strategy, rats were killed under light ether anesthesia. At that stage, the blood sample collected from rats linked to the various collections and allowed the typical room temperature coagulation.…”

Effects of Silymarin on Diabetes Mellitus Complications: A Review

“…Several articles have reported the findings of in vitro , in vivo , and clinical studies of silymarin and its constituent compounds and found that its main beneficial action involves antioxidant effects in different organs and diseases. Different mechanistic explanations for the antioxidant effects of silymarin have been described, including (i) preventing free radical formation by inhibiting specific reactive oxygen species (ROS)‐producing enzymes or improving the integrity of mitochondria in conditions of stress, (ii) decreasing inflammatory responses by inhibiting nuclear factor κB (NF‐κB)‐dependent pathways, and (iii) maintaining an optimal redox balance in the cell by activating a range of antioxidant enzymes and non‐enzymatic antioxidants, mainly via the activation of nuclear factor‐erythroid two‐related factor (Nrf2; Surai, ; Tan et al , ; Zhao et al ., ; Fallahzadeh et al , ; Salamone et al ., ; Soto et al , ; Vengerovskii et al, ). Growing evidence indicates that the Nrf2 antioxidant response plays an important role in cellular defense by activating a wide variety of genes that are involved in early antioxidant defense reactions (Surai, ), inflammatory processes, apoptotic processes, metabolism, detoxification, and cellular proliferation (Morales‐Gonzáles et al ., ).…”