Silymarin alleviates bleomycin-induced pulmonary toxicity and lipid peroxidation in mice

Abstract

Context: The application of bleomycin is limited due to its side effects including lung toxicity. Silymarin is a flavonoid complex isolated from milk thistle [Silybum marianum L. (Asteraceae)] which has been identified as an antioxidant and anti-inflammatory compound.Objective: This study evaluates the effect of silymarin on oxidative and inflammatory parameters in the lungs of mice exposed to bleomycin. Materials and methods: BALB/c mice were divided into four groups of control, bleomycin (1.5 U/kg), bleomycin plus silymarin (50 and 100 mg/kg). After bleomycin administration, mice received 10 d intraperitoneal silymarin treatment. On 10th day, blood and lung samples were collected for measurement of oxidative and inflammatory factors. Results: Silymarin led to a decrease in lung lipid peroxidation (0.19 and 0.17 nmol/mg protein) in bleomycin-injected animals. Glutathione-S-transferase (GST) which was inhibited by bleomycin (32.4 nmol/min/mg protein) induced by higher dose of silymarin (41 nmol/min/mg protein). Silymarin caused an elevation in glutathione (GSH): 2.6 and 3.1 mmol/g lung compare with bleomycin-injected animals 1.8 mmol/g lung. Catalase (CAT) was increased due to high dose of silymarin (65.7 mmol/min/ml protein) compare with bleomycin treated-mice. Myeloperoxidase (MPO) which was induced due to bleomycin (p50.05) reduced again by high dose of silymarin (0.51 U/min/mg protein). Bleomycin led to an increase in TNF-a and interleukin-6 (IL-6) (7.9 and 11.8 pg/ml). These parameters were reduced by silymarin (p50.05). Conclusions: Silymarin attenuated bleomycin induced-pulmonary toxicity. This protective effect may be due to the ability of silymarin in keeping oxidant-antioxidant balance and regulating of inflammatory mediator release.

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

“…23,24 Furthermore, reduced MPO activity was also detected in a mouse model of bleomycin induced-pulmonary toxicity that was treated with silymarin. 25 The present study demonstrates that PQ administration caused lung histopathological changes, including infiltration of inflammatory cells, thickening of alveolar septum and collagen accumulation, which are in line with previous findings. 26,27 However, our experiments revealed that lung injury and inflammatory responses (the infiltration of neutrophils and macrophages) in lung tissue were effectively alleviated by silymarin administration.…”

“…A previous finding has shown that silymarin pre‐treatment effectively attenuates cigarette smoke‐induced chronic obstructive pulmonary disease in BALB/c mice through suppressing pathological changes, oxidative stress and inflammatory cell infiltration, along with a decreased MPO activity (an indicator of neutrophil infiltration and activation) . Furthermore, reduced MPO activity was also detected in a mouse model of bleomycin induced‐pulmonary toxicity that was treated with silymarin . The present study demonstrates that PQ administration caused lung histopathological changes, including infiltration of inflammatory cells, thickening of alveolar septum and collagen accumulation, which are in line with previous findings .…”

Anti-Fibrotic Potential of Nicorandil in the Treatment of Bleomycin Induced Pulmonary Fibrosis

“…In addition, several studies have demonstrated that bleomycin administration in rats decreased the anti-oxidative capacity and increased oxidative stress in the lung tissue, which aggravated pulmonary fibrosis. 13,14,15 It has been established that in bleomycin induced pulmonary fibrosis the levels of the biochemical, oxidant and antioxidant parameters changed significantly than those of the normal levels. This is evident by increased levels Lactate Dehydrogenase (LDH) which is a marker of biochemical index.…”

“…Previous studies demonstrated that anti-oxidant agents ameliorated the accumulation of leukocytes in bronchial lavage fluid and lung tissue which agrees with our findings. [12][13][14][15][16][17][18][19] The pathophysiology of Bleomycin-induced lung injury typically consisted of two overlapping stages; an early inflammatory phase characterized by leukocyte infiltration and injury to alveolar epithelial cells, and a subsequent fibro-proliferative phase with matrix remodeling and fibrosis. 20 Haematoxylin & Eosin (H&E) staining results in BLM control group showed that acute inflammations were prominent with moderate or severe hemorrhage, widened alveolar septa, and infiltration of numerous inflammatory cells predominated by macrophages, neutral granulocytes, and lymphocytes.…”

Untitled

“…LPO is considered as the prime rationale that instigates lung injury 35 . The most commonly used lipid peroxidation markers are TBARS as MDA.…”