Biological Trace Element Research

, Volume 183, Issue 1, pp 80–91 | Cite as

Alleviation of Arsenic-Induced Pulmonary Oxidative Damage by GSPE as Shown during In vivo and In vitro Experiments

  • Meng Wei
  • Fangming Guo
  • Dongsheng Rui
  • Haixia Wang
  • Gangling Feng
  • Shugang Li
  • Guanling Song


A long-term exposure to arsenic may lead to lung damage due to oxidative stress. In this context, GSPE can play a major role as a strong antioxidant. Our study attempted to reveal the connection between arsenic-induced lung injury and the antagonistic effect of GSPE. For this purpose, BEAS-2B cells and Kunming mice were exposed to different dosages of As2O3 and GSPE. Oxidative stress indicators were detected both in vivo and in vitro. Cell survival rate and morphological changes in the lung tissue (H&E staining) were evaluated as well. It was exhibited that As2O3 increased oxidative stress both in vivo and in vitro and decreased cells viability. In contrast, higher cell survival rate was revealed in the group treated with arsenic plus GSPE after 24 h as compared to that in the arsenic group. GSPE effectively reduced oxidative stress levels, along with increasing antioxidant capacity. In vivo experiments in arsenic-exposed group showed alveolar septum to be significantly thickened with considerable capillary congestion and invasion by inflammatory cells. After the intervention with GSPE, there seemed to be a dramatic reversal of morphology with thinning of the alveolar septum, decrease in capillary congestion, and number of inflammatory cells. This had shown that GSPE can effectively reduce the levels of oxidative stress, induced by arsenic in mice lung tissue. Conversely, antioxidant enzymes or products were increased. The experiment proved that GSPE can protect the lungs from oxidative damage induced by arsenic, and it may also be used as an antagonist against arsenic injuries.


Arsenic Oxidative damage GSPE Mice lung tissues 



The authors would like to thank the Department of Public Health, Shihezi University School of Medicine for assistance with this work, as well as funding from National Natural Science Foundation of China (No. 81560517), the Key Areas of Science and Technology Research Project of Xinjiang Production and Construction Corps (No. 2015AG014, No.2014BA039) and the International Cooperative Project of Shihezi University (No. GJHZ201602).

Author’s Contribution

Experiments conceived and designed by SL MW FG and performed by MW, FG, DR, HW, GF, SL, GS. Analyses of the data are performed by SL, DR. Reagents, materials, and analysis tools were contributed by MW, GS, SL, and FG. The manuscript was written by SL, MW, and FG and revised by SL and GS.

Compliance with Ethical Standards

The present research was approved by the Ethical Committee of the First Affiliated Hospital of School of Medicine, Shihezi University (Approval ID: 2015-076-01). In this study, we were permitted to collect the blood samples and lung tissues of mice to detect the biochemical parameters.

Conflict of Interests

The authors declare that they have no conflict of interest.


  1. 1.
    Lynch HN, Zua K, Kennedy EM, Lam T, Liu X, Pizzurro DM, Loftus CT, Rhomberga LR (2017) Quantitative assessment of lung and bladder cancer risk and oral exposure to inorganic arsenic: meta-regression analyses of epidemiological data. Environ Int 106:178–206. doi: 10.1016/j.envint.2017.04.008 CrossRefPubMedGoogle Scholar
  2. 2.
    Ferreccio C, Smith AH, Durán V, Barlaro T, Benítez H, Valdés R, Aguirre JJ, Moore LE, Acevedo J, Vásquez MI, Pérez L, Yuan Y, Liaw J, Cantor KP, Steinmaus C (2013) Case-control study of arsenic in drinking water and kidney cancer in uniquely exposed northern Chile. Am J Epidemiol 178(5):813–818CrossRefPubMedPubMedCentralGoogle Scholar
  3. 3.
    Wang W, Cheng S, Zhang D (2014) Association of inorganic arsenic exposure with liver cancer mortality: a meta-analysis. Environ Res 135(2):120–125CrossRefPubMedGoogle Scholar
  4. 4.
    Tanaka-Kagawa T, Hanioka N, Yoshida H, Jinno H, Ando M (2015) Arsenite and arsenate activate extracellular signal-regulated kinases 1/2 by an epidermal growth factor receptor-mediated pathway in normal human keratinocytes. Br J Dermatol 149(6):1116–1127CrossRefGoogle Scholar
  5. 5.
    Bulka CM, JonesR M, Turyk ME, Stayner LT, Argos M (2016) Arsenic in drinking water and prostate cancer in Illinois counties: an ecologic study. Environ Res 148:450–465CrossRefPubMedPubMedCentralGoogle Scholar
  6. 6.
    Rahman A, Vahter M, Ekström EC, Persson LÅ (2011) Arsenic exposure in pregnancy increases the risk of lower respiratory tract infection and diarrhea during infancy in Bangladesh. Environ Health Perspect 119(5):719–724CrossRefPubMedGoogle Scholar
  7. 7.
    Yadav RS, Chandravanshi LP, Shukla RK, Sankhwar ML, Ansari RW, Shukla PK (2011) Neuroprotective efficacy of curcumin in arsenic induced cholinergic dysfunctions in rats. Neurotoxicology 32(6):760–768CrossRefPubMedGoogle Scholar
  8. 8.
    Srivastava P, Yadav RS, Chandravanshi LP, Shukla RK, Dhuriya YK, Chauhan LK (2014) Unraveling the mechanism of neuroprotection of curcumin in arsenic induced cholinergic dysfunctions in rats. Toxicol Appl Pharmacol 279(3):428–440CrossRefPubMedGoogle Scholar
  9. 9.
    Mandal BK, Suzuki KT (2002) Arsenic round the world: a review. Talanta 58(1):201–235CrossRefPubMedGoogle Scholar
  10. 10.
    Steinmaus C, Ferreccio C, Acevedo J, Balmes JR, Liaw J, Troncoso P, Dauphiné DC, Nardone A, Smith AH (2016) High risks of lung disease associated with early-life and moderate lifetime arsenic exposure in northern Chile. Toxicol Appl Pharmacol 313:10–15CrossRefPubMedPubMedCentralGoogle Scholar
  11. 11.
    Li S, Ding Y, Niu Q, Xu S, Pang L, Ma R, Jing M, Feng G, Wei M, Li F, Guo S (2015) Grape seed proanthocyanidin extract alleviates arsenic-induced oxidative reproductive toxicity in male mice. Biomed Environ Sci 28(4):272–280PubMedGoogle Scholar
  12. 12.
    Shen H, Niu Q, Xu M, Rui D, Xu S, Feng G, Ding Y, Li S, Jing M (2016) Factors affecting arsenic methylation in arsenic-exposed humans: a systematic review and meta-analysis. Int J Environ Res Public Health 13(2):205CrossRefPubMedPubMedCentralGoogle Scholar
  13. 13.
    Li S, Ma R, Niu Q, Xu S, Pang L, Ding Y, Lati M, Jing M, Feng G, Liu JM, Wang H, Li F, Guo S (2015) The relationship between liver dysfunction and arsenic methylation in mice. Pol J Environ Stud 24(4):1667–1676CrossRefGoogle Scholar
  14. 14.
    Li SG, Xu SZ, Niu Q, Ding YS, Pang LJ, Ma RL, Jing MX, Wang K, Ma XM, Feng GL, Liu JM, Zhang XF, Xiang HL, Li F, Guo SX (2015) Lutein alleviates arsenic-induced reproductive toxicity in male mice via Nrf2 signaling. Hum Exp Toxicol 35(5):491–499CrossRefPubMedGoogle Scholar
  15. 15.
    Wang DP, Wang SX, Wang ZH, Zhang LM, Li J, Liu J (2011) The arsenic concentration in saliva, urine and drinking water in endemic arsenicosis area in Shanyin County of Shanxi Province, China. Appl Mech Mater 140(2):465–468CrossRefGoogle Scholar
  16. 16.
    Jin X, Su R, Li R, Song L, Chen M, Cheng L (2015) Amelioration of particulate matter-induced oxidative damage by vitamin c and quercetin in human bronchial epithelial cells. Chemosphere 144:459–466CrossRefPubMedGoogle Scholar
  17. 17.
    Ourique GM, Saccol EMH, Pês TS, Glanzner WG, Sun HS, Woehl VM (2016) Protective effect of vitamin E on sperm motility and oxidative stress in valproic acid treated rats. Food Chem Toxicol 95:159–167CrossRefPubMedGoogle Scholar
  18. 18.
    Li S, Xu M, Niu Q, Xu S, Ding Y, Yan Y, Li F, Guo S (2015) Efficacy of Procyanidins against in vivo cellular oxidative damage: a systematic review and meta-analysis. PLoS One 10(10):e0139455CrossRefPubMedPubMedCentralGoogle Scholar
  19. 19.
    Li C, Li S, Niu Q, Xu S, Ding Y, Wang X (2016) Procyanidin protects against arsenic-induced liver injury in mice. J Toxicol 30(1):14–17Google Scholar
  20. 20.
    Zhang B, Li S, Niu Q, Ding Y, Guo S, Xu S (2014) Greap seed extract procyanidins has a antagonism effect on hepatotoxicity induced by arsenic in mile mice. J Tox 28(5):397–400Google Scholar
  21. 21.
    Zhou Q, Yin ZP, Ma L, Zhao W, Hao HW, Li HL (2014) Free radical-scavenging activities of oligomeric proanthocyanidin from Rhodiola Rosea L. and its antioxidant effects in vivo. Nat Prod Res 28(24):1–3CrossRefGoogle Scholar
  22. 22.
    Zhang Z, Pratheeshkumar P, Budhraja A, Son Y-O, Kim D, Shi X (2015) Role of reactive oxygen species in arsenic-induced transformation of human lung bronchial epithelial (BEAS-2B) cells. Biochem Biophys Res Commun 156(2):643–648CrossRefGoogle Scholar
  23. 23.
    Zhou Y, Ye X, Shi Y, Wang K, Wan D (2016) Grape seed proanthocyanidins inhibits the invasion and migration of A549 lung cancer cells. Chin J Cell Mol Immunol 32(2):173–181Google Scholar
  24. 24.
    Grabie N, Delfs MW, Westrich JR, Love VA, Stavrakis G, Ahmad F (2003) IL-12 is required for differentiation of pathogenic CD8+ T cell effectors that cause myocarditis. J Clin Investig 111(5):671–680CrossRefPubMedPubMedCentralGoogle Scholar
  25. 25.
    Christoforidou EP, Riza E, Kales SN, Hadjistavrou K, Stoltidi M, Kastania AN (2013) Bladder cancer and arsenic through drinking water: a systematic review of epidemiologic evidence. J Environ Sci Health Tox Hazard Subst Environ Eng 48(14):1764–1775CrossRefGoogle Scholar
  26. 26.
    Saha JC, Dikshit AK, Bandyopadhyay M, Saha KC (1999) A review of arsenic poisoning and its effects on human health. Crit Rev Environ Sci Technol 29(29)Google Scholar
  27. 27.
    Ghosh SK, Bandyopadhyay D, Bandyopadhyay SK, Debbarma K (2013) Cutaneous malignant and premalignant conditions caused by chronic arsenicosis from contaminated ground water consumption: a profile of patients from eastern India. Skinmed 11(4):211–216PubMedGoogle Scholar
  28. 28.
    Ghosh A (2013) Evaluation of chronic arsenic poisoning due to consumption of contaminated ground water in West Bengal, India. Int J Prev Med 4(8):976–979PubMedPubMedCentralGoogle Scholar
  29. 29.
    Ghazi HS, Habibiyan M, Moeini MM, Abdolmohammadi AR (2012) Effects of dietary selenium, vitamin E, and their combination on growth, serum metabolites, and antioxidant defense system in skeletal muscle of broilers under heat stress. Biol Trace Elem Res 148(3):322–330CrossRefGoogle Scholar
  30. 30.
    Flora SJ, Flora G, Saxena G, Mishra M (2007) Arsenic and lead induced free radical generation and their reversibility following chelation. Cell Mol Biol (Noisy-le-Grand, France) 53(1):26–47Google Scholar
  31. 31.
    Jia Z, Song Z, Zhao Y, Wang X, Liu P (2011) Grape seed proanthocyanidin extract protects human lens epithelial cells from oxidative stress via reducing NF-кB and MAPK protein expression. Mol Vis 17:210–217PubMedPubMedCentralGoogle Scholar
  32. 32.
    Zhao YM, Zhao JY, Gao PL (2015) Protective effects of grape seed proanthocyanidin extract(GSPE) on cis-diamminedichloroplatinum (CDDP)-induced renal oxidative damage and mitochondrial injury in rats. Mod Food Sci Technol 31(1)Google Scholar
  33. 33.
    Danh LT, Truong P, Mammucari R, Foster N (2014) A critical review of the arsenic uptake mechanisms and phytoremediation potential of Pteris vittata. Int J Phytoremediation 16(5):429–453CrossRefPubMedGoogle Scholar
  34. 34.
    Malik JA, Goel S, Kaur N, Sharma S, Singh I, Nayyar H (2011) Selenium antagonises the toxic effects of arsenic on mungbean ( Phaseolus aureus, Roxb.) plants by restricting its uptake and enhancing the antioxidative and detoxification mechanisms. Environ Exp Bot 77(2):42–48Google Scholar
  35. 35.
    Waghe P, Sarath TS, Gupta P, Kutty HS, Kandasamy K, Mishra SK (2014) Subchronic arsenic exposure through drinking water alters vascular redox homeostasis and affects physical health in rats. Biol Trace Elem Res 162(1–3):234–241CrossRefPubMedGoogle Scholar
  36. 36.
    Klauser E, Gülden M, Maser E, Seibert S, Seibert H (2014) Additivity, antagonism, and synergy in arsenic trioxide-induced growth inhibition of C6 glioma cells: effects of genistein, quercetin and buthionine-sulfoximine. Food Chem Toxicol 67(5):212–221CrossRefPubMedGoogle Scholar
  37. 37.
    Cozic A, Viollier E, Chiffoleau JF, Knoery J, Rozuel E (2008) Interactions between volatile reduced sulfur compounds and metals in the seine estuary (France). Estuar Coasts 31(6):1063–1071CrossRefGoogle Scholar
  38. 38.
    Özk G, Ulusoy S, Alkanat M, Orem A, Akc B, Ersöz Ş (2012) Antiapoptotic and antioxidant effects of GSPE in preventing cyclosporine A-induced cardiotoxicity. Ren Fail 34(4):460–466CrossRefGoogle Scholar
  39. 39.
    Li S, Xu S, Niu Q, Ding Y, Pang L, Ma R (2016) Lutein alleviates arsenic-induced reproductive toxicity in male mice via Nrf2 signaling. Hum Exp Toxicol 35(5):491–495CrossRefPubMedGoogle Scholar
  40. 40.
    Yan S, Xiu C, Wei L, Yuan T, Wang J, Qu YI (2016) Grape seed proanthocyanidin extract protects the retina against early diabetic injury by activating the Nrf2 pathway. Exp Ther Med 11(4):1253–1258CrossRefGoogle Scholar
  41. 41.
    Srivastava P, Dhuriya YK, Gupta R, Shukla RK, Yadav RS, Dwivedi HN, Pant AB, Khanna VK (2016) Protective effect of curcumin by modulating BDNF/DARPP32/CREB in arsenic-induced alterations in dopaminergic signaling in rat corpus striatum. Mol Neurobiol 1–17. doi: 10.1007/s12035-016-0288-2
  42. 42.
    Zhong Y, Chen T, Zheng W, Yang Y (2015) Selenium enhances antioxidant activity and photosynthesis in Ulva Fasciata. J Appl Phycol 27(1):555–562CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2017

Authors and Affiliations

  1. 1.Shihezi University School of MedicineShiheziChina

Personalised recommendations