Login Register Cart 0
Generic placeholder image

Combinatorial Chemistry & High Throughput Screening

Editor-in-Chief

ISSN (Print): 1386-2073
ISSN (Online): 1875-5402

Back
Journal Home About Journal Editorial Board Journal Insight Current Issue Volumes/Issues
Subscribe
Research Article

Ziziphus spina-christi Leaf Extract Mitigates Mercuric Chloride-induced Cortical Damage in Rats

Author(s): Rafa S. Almeer*, Saad Alkahtani, Saud Alarifi, Ahmed E. Abdel Moneim, Saba Abdi and Gadah Albasher

Volume 25, Issue 1, 2022

Published on: 04 December, 2020

Page: [103 - 113] Pages: 11

DOI: 10.2174/1386207323666201204124412

Price: $65

Abstract

Background: Mercuric chloride (HgCl2) severely impairs the central nervous system when humans are exposed to it.

Aims: We investigated the neuroprotective efficiency of Ziziphus spina-christi leaf extract (ZSCLE) on HgCl2-mediated cortical deficits.

Methods: Twenty-eight rats were distributed equally into four groups: the control, ZSCLE-treated (300 mg/kg), HgCl2-treated (0.4 mg/kg), and ZSCLE+HgCl2-treated groups. Animals received their treatments for 28 days.

Results: Supplementation with ZSCLE after HgCl2 exposure prevented the deposition of mercury in the cortical slices. It also lowered malondialdehyde levels and nitrite and nitrate formation, elevated glutathione levels, activated its associated-antioxidant enzymes, glutathione reductase, and glutathione peroxidase, and upregulated the transcription of catalase and superoxide dismutase and their activities were accordingly increased. Moreover, ZSCLE activated the expression of nuclear factor erythroid 2-related factor 2 and heme oxygenase-1 when compared with the HgCl2 group. Notably, post-treatment with ZSCLE increased the activity of acetylcholinesterase and ameliorated the histopathological changes associated with HgCl2 exposure. Furthermore, ZSCLE blocked cortical inflammation, as observed by the lowered mRNA expression and protein levels of interleukin-1 beta and tumor necrosis factor-alpha, as well as decreased mRNA expression of inducible nitric oxide synthase. In addition, ZSCLE decreased neuron loss by preventing apoptosis in the cortical tissue upon HgCl2 intoxication.

Conclusion: Based on the obtained findings, we suggest that ZSCLE supplementation could be applied as a neuroprotective agent to decrease neuron damage following HgCl2 toxicity.

Keywords: Mercury, Ziziphus spina-christi, brain, Nrf2, inflammation, apoptosis.

« Previous Next »
Graphical Abstract

[1]
Bernhoft, R.A. Mercury toxicity and treatment: a review of the literature. J. Environ. Public Health, 2012, 2012, 460508.
[http://dx.doi.org/10.1155/2012/460508] [PMID: 22235210]
[2]
Caglayan, C.; Kandemir, F.M.; Darendelioğlu, E.; Yıldırım, S.; Kucukler, S.; Dortbudak, M.B. Rutin ameliorates mercuric chloride-induced hepatotoxicity in rats via interfering with oxidative stress, inflammation and apoptosis. J. Trace Elem. Med. Biol., 2019, 56, 60-68.
[http://dx.doi.org/10.1016/j.jtemb.2019.07.011] [PMID: 31442956]
[3]
Yadav, H.N.; Sharma, U.S.; Singh, S.; Gupta, Y.K. Effect of Tribulus terrestris in mercuric chloride-induced renal accumulation of mercury and nephrotoxicity in rat. J. Adv. Pharm. Technol. Res., 2019, 10(3), 132-137.
[http://dx.doi.org/10.4103/japtr.JAPTR_386_18] [PMID: 31334096]
[4]
Genchi, G.; Sinicropi, M.S.; Carocci, A.; Lauria, G.; Catalano, A. Mercury exposure and heart diseases. Int. J. Environ. Res. Public Health, 2017, 14(1), E74.
[http://dx.doi.org/10.3390/ijerph14010074] [PMID: 28085104]
[5]
Koopsamy Naidoo, S.V.; Bester, M.J.; Arbi, S.; Venter, C.; Dhanraj, P.; Oberholzer, H.M. Oral exposure to cadmium and mercury alone and in combination causes damage to the lung tissue of Sprague-Dawley rats. Environ. Toxicol. Pharmacol., 2019, 69, 86-94.
[http://dx.doi.org/10.1016/j.etap.2019.03.021] [PMID: 30981014]
[6]
Ye, B.J.; Kim, B.G.; Jeon, M.J.; Kim, S.Y.; Kim, H.C.; Jang, T.W.; Chae, H.J.; Choi, W.J.; Ha, M.N.; Hong, Y.S. Evaluation of mercury exposure level, clinical diagnosis and treatment for mercury intoxication. Ann. Occup. Environ. Med., 2016, 28, 5.
[http://dx.doi.org/10.1186/s40557-015-0086-8] [PMID: 26807265]
[7]
Xu, F.; Farkas, S.; Kortbeek, S.; Zhang, F-X.; Chen, L.; Zamponi, G.W.; Syed, N.I. Mercury-induced toxicity of rat cortical neurons is mediated through N-Methyl-D-Aspartate receptors. Mol. Brain, 2012, 5(1), 30.
[http://dx.doi.org/10.1186/1756-6606-5-30] [PMID: 22980357]
[8]
Abdel Moneim, A.E. The neuroprotective effect of berberine in mercury-induced neurotoxicity in rats. Metab. Brain Dis., 2015, 30(4), 935-942.
[http://dx.doi.org/10.1007/s11011-015-9652-6] [PMID: 25600690]
[9]
Moneim, A.E. Mercury-induced neurotoxicity and neuroprotective effects of berberine. Neural Regen. Res., 2015, 10(6), 881-882.
[http://dx.doi.org/10.4103/1673-5374.158336] [PMID: 26199596]
[10]
Teixeira, FB; Fernandes, RM; Farias-Junior, PM; Costa, NM; Fernandes, LM; Santana, LN; Silva-Junior, AF; Silva, MC; Maia, CS; Lima, RR Evaluation of the effects of chronic intoxication with inorganic mercury on memory and motor control in rats. Int. J. Environ. Res. Public Health, 2014, 11(9), 9171-9185.
[http://dx.doi.org/10.3390/ijerph110909171]
[11]
Al Omairi, N.E.; Radwan, O.K.; Alzahrani, Y.A.; Kassab, R.B. Neuroprotective efficiency of Mangifera indica leaves extract on cadmium-induced cortical damage in rats. Metab. Brain Dis., 2018, 33(4), 1121-1130.
[http://dx.doi.org/10.1007/s11011-018-0222-6] [PMID: 29557530]
[12]
Al Olayan, E.M.; Aloufi, A.S.; AlAmri, O.D.; El-Habit, O.H.; Abdel Moneim, A.E. Protocatechuic acid mitigates cadmium-induced neurotoxicity in rats: Role of oxidative stress, inflammation and apoptosis. Sci. Total Environ., 2020, 723, 137969.
[http://dx.doi.org/10.1016/j.scitotenv.2020.137969] [PMID: 32392679]
[13]
Al-Megrin, W.A.; Soliman, D.; Kassab, R.B.; Metwally, D.M.; El-Khadragy, M.F.; Ahmed, E. Abdel Moneim. Coenzyme Q10 activates the antioxidant machinery and inhibits the inflammatory and apoptotic cascades against lead acetate-induced renal injury in rats. Front. Physiol., 2020, 11(64), 64.
[http://dx.doi.org/10.3389/fphys.2020.00064] [PMID: 32116774]
[14]
Saied, A.S.; Gebauer, J.; Hammer, K.; Buerkert, A. Ziziphus spina-christi (L.) Willd.: a multipurpose fruit tree. Genet. Resour. Crop Evol., 2008, 55(7), 929-937.
[http://dx.doi.org/10.1007/s10722-007-9299-1]
[15]
Amin, AR; Kassab, RB; Abdel Moneim, AE Amin, HK Comparison Among garlic, berberine, resveratrol, hibiscus sabdariffa, genus zizyphus, hesperidin, red beetroot, catha edulis, portulaca oleracea, and mulberry leaves in the treatment of hypertension and type 2 dm: a comprehensive review. Natural Product Communications, 2020, 15(4)
[16]
Asgarpanah, J.; Haghighat, E. Phytochemistry and pharmacologic properties of Ziziphus spina christi (L.) Willd. Afr. J. Pharm. Pharmacol., 2012.
[http://dx.doi.org/10.5897/AJPP12.509]
[17]
Dkhil, M.A.; Al-Quraishy, S.; Moneim, A.E.A. Ziziphus spina-christi leaf extract pretreatment inhibits liver and spleen injury in a mouse model of sepsis via anti-oxidant and anti-inflammatory effects. Inflammopharmacology, 2018, 26(3), 779-791.
[http://dx.doi.org/10.1007/s10787-017-0439-8] [PMID: 29327282]
[18]
Dkhil, MA; Kassab, RB; Al-Quraishy, S; Abdel-Daim, MM; Zrieq, R Abdel Moneim, AE Ziziphus spina-christi (L.) leaf extract alleviates myocardial and renal dysfunction associated with sepsis in mice. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie, 2018, 102, 64-75.
[19]
Almeer, R.S.; Mahmoud, S.M.; Amin, H.K.; Abdel Moneim, A.E. Ziziphus spina-christi fruit extract suppresses oxidative stress and p38 MAPK expression in ulcerative colitis in rats via induction of Nrf2 and HO-1 expression. Food Chem. Toxicol., 2018, 115, 49-62.
[http://dx.doi.org/10.1016/j.fct.2018.03.002] [PMID: 29518435]
[20]
Lowry, O.H.; Rosebrough, N.J.; Farr, A.L.; Randall, R.J. Protein measurement with the Folin phenol reagent. J. Biol. Chem., 1951, 193(1), 265-275.
[PMID: 14907713]
[21]
Baxter, D.C.; Frech, W. Determination of mercury by atomic absorption spectrometry using a platinum-lined graphite furnace for in situ preconcentration. Anal. Chim. Acta, 1989, 225, 175-183.
[http://dx.doi.org/10.1016/S0003-2670(00)84605-X]
[22]
Ellman, G.L.; Courtney, K.D.; Andres, V., Jr; Feather-Stone, R.M. A new and rapid colorimetric determination of acetylcholinesterase activity. Biochem. Pharmacol., 1961, 7, 88-95.
[http://dx.doi.org/10.1016/0006-2952(61)90145-9] [PMID: 13726518]
[23]
Ohkawa, H.; Ohishi, N.; Yagi, K. Assay for lipid peroxides in animal tissues by thiobarbituric acid reaction. Anal. Biochem., 1979, 95(2), 351-358.
[http://dx.doi.org/10.1016/0003-2697(79)90738-3] [PMID: 36810]
[24]
Bryan, NS; Grisham, MB Methods to detect nitric oxide and its metabolites in biological samples. Free Rad. Biol. Med., 2007, 43(5), 645-657.
[http://dx.doi.org/10.1016/j.freeradbiomed.2007.04.026]
[25]
Ellman, G.L. Tissue sulfhydryl groups. Arch. Biochem. Biophys., 1959, 82(1), 70-77.
[http://dx.doi.org/10.1016/0003-9861(59)90090-6] [PMID: 13650640]
[26]
Paglia, D.E.; Valentine, W.N. Studies on the quantitative and qualitative characterization of erythrocyte glutathione peroxidase. J. Lab. Clin. Med., 1967, 70(1), 158-169.
[PMID: 6066618]
[27]
De Vega, L.; Férnandez, R.P.; Mateo, M.C.; Bustamante, J.B.; Herrero, A.M.; Munguira, E.B. Glutathione determination and a study of the activity of glutathione-peroxidase, glutathione-transferase, and glutathione-reductase in renal transplants. Ren. Fail., 2002, 24(4), 421-432.
[http://dx.doi.org/10.1081/JDI-120006769] [PMID: 12212822]
[28]
Nishikimi, M.; Appaji, N.; Yagi, K. The occurrence of superoxide anion in the reaction of reduced phenazine methosulfate and molecular oxygen. Biochem. Biophys. Res. Commun., 1972, 46(2), 849-854.
[http://dx.doi.org/10.1016/S0006-291X(72)80218-3] [PMID: 4400444]
[29]
Aebi, H. Catalase in vitro. Methods Enzymol., 1984, 105, 121-126.
[http://dx.doi.org/10.1016/S0076-6879(84)05016-3] [PMID: 6727660]
[30]
Al-Quraishy, S.; Dkhil, M.A.; Abdel-Gaber, R.; Zrieq, R.; Hafez, T.A.; Mubaraki, M.A.; Abdel Moneim, A.E. Myristica fragrans seed extract reverses scopolamine-induced cortical injury via stimulation of HO-1 expression in male rats. Environ. Sci. Pollut. Res. Int., 2020, 27(11), 12395-12404. [pii].
[http://dx.doi.org/10.1007/s11356-020-07686-8] [PMID: 31993909]
[31]
Aragão, W.A.B.; Teixeira, F.B.; Fagundes, N.C.F.; Fernandes, R.M.; Fernandes, L.M.P.; da Silva, M.C.F.; Amado, L.L.; Sagica, F.E.S.; Oliveira, E.H.C.; Crespo-Lopez, M.E.; Maia, C.S.F.; Lima, R.R. Hippocampal dysfunction provoked by mercury chloride exposure: evaluation of cognitive impairment, oxidative stress, tissue injury and nature of cell death. Oxid. Med. Cell. Longev., 2018, 2018, 7878050.
[http://dx.doi.org/10.1155/2018/7878050] [PMID: 29849915]
[32]
Moraes-Silva, L.; Siqueira, L.F.; Oliveira, V.A.; Oliveira, C.S.; Ineu, R.P.; Pedroso, T.F.; Fonseca, M.M.; Pereira, M.E. Preventive effect of CuCl2 on behavioral alterations and mercury accumulation in central nervous system induced by HgCl2 in newborn rats. J. Biochem. Mol. Toxicol., 2014, 28(7), 328-335.
[http://dx.doi.org/10.1002/jbt.21569] [PMID: 24799335]
[33]
Weis, J.; Smith, G.; Zhou, T.; Bass, C.; Weis, P. Effects of contaminants on behavior: biochemical mechanisms and ecological consequences. Bioscience, 2009, 51, 209-217.
[http://dx.doi.org/10.1641/0006-3568(2001)051[0209:EOCOBB]2.0.CO;2]
[34]
Almeer, R.S.; Albasher, G.; Kassab, R.B.; Ibrahim, S.R.; Alotibi, F.; Alarifi, S.; Ali, D.; Alkahtani, S.; Abdel Moneim, A.E. Ziziphus spina-christi leaf extract attenuates mercury chloride-induced testicular dysfunction in rats. Environ. Sci. Pollut. Res. Int., 2020, 27(3), 3401-3412. [pii].
[http://dx.doi.org/10.1007/s11356-019-07237-w] [PMID: 31840221]
[35]
Abdel Moneim, A.E. Indigofera oblongifolia prevents lead acetate-induced hepatotoxicity, oxidative stress, fibrosis and apoptosis in rats. PLoS One, 2016, 11(7), e0158965.
[http://dx.doi.org/10.1371/journal.pone.0158965] [PMID: 27391413]
[36]
Franciscato, C.; Goulart, F.R.; Lovatto, N.M.; Duarte, F.A.; Flores, E.M.; Dressler, V.L.; Peixoto, N.C.; Pereira, M.E. ZnCl2 exposure protects against behavioral and acetylcholinesterase changes induced by HgCl2. Int. J. Dev. Neurosci., 2009, 27(5), 459-468.
[http://dx.doi.org/10.1016/j.ijdevneu.2009.05.002] [PMID: 19446626]
[37]
Al Omairi, N.E.; Al-Brakati, A.Y.; Kassab, R.B.; Lokman, M.S.; Elmahallawy, E.K.; Amin, H.K.; Abdel Moneim, A.E. Soursop fruit extract mitigates scopolamine-induced amnesia and oxidative stress via activating cholinergic and Nrf2/HO-1 pathways. Metab. Brain Dis., 2019, 34(3), 853-864.
[http://dx.doi.org/10.1007/s11011-019-00407-2] [PMID: 30919246]
[38]
Abu-Taweel, G.M. Neurobehavioral protective properties of curcumin against the mercury chloride treated mice offspring. Saudi J. Biol. Sci., 2019, 26(4), 736-743.
[http://dx.doi.org/10.1016/j.sjbs.2018.10.016] [PMID: 31048998]
[39]
Ceccatelli, S.; Daré, E.; Moors, M. Methylmercury-induced neurotoxicity and apoptosis. Chem. Biol. Interact., 2010, 188(2), 301-308.
[http://dx.doi.org/10.1016/j.cbi.2010.04.007] [PMID: 20399200]
[40]
Almeer, R.S.; Kassab, R.B.; AlBasher, G.I.; Alarifi, S.; Alkahtani, S.; Ali, D.; Abdel Moneim, A.E. Royal jelly mitigates cadmium-induced neuronal damage in mouse cortex. Mol. Biol. Rep., 2019, 46(1), 119-131.
[http://dx.doi.org/10.1007/s11033-018-4451-x] [PMID: 30414103]
[41]
Stohs, S.J.; Bagchi, D. Oxidative mechanisms in the toxicity of metal ions. Free Radic. Biol. Med., 1995, 18(2), 321-336.
[http://dx.doi.org/10.1016/0891-5849(94)00159-H] [PMID: 7744317]
[42]
Hickey, M.J.; Granger, D.N.; Kubes, P. Inducible nitric oxide synthase (iNOS) and regulation of leucocyte/endothelial cell interactions: studies in iNOS-deficient mice. Acta Physiol. Scand., 2001, 173(1), 119-126.
[http://dx.doi.org/10.1046/j.1365-201X.2001.00892.x] [PMID: 11678734]
[43]
Ferreiro, C.R.; Chagas, A.C.; Carvalho, M.H.; Dantas, A.P.; Jatene, M.B.; Bento De Souza, L.C.; Lemos Da Luz, P. Influence of hypoxia on nitric oxide synthase activity and gene expression in children with congenital heart disease: a novel pathophysiological adaptive mechanism. Circulation, 2001, 103(18), 2272-2276.
[http://dx.doi.org/10.1161/01.CIR.103.18.2272] [PMID: 11342476]
[44]
Pollard, KM; Cauvi, DM; Toomey, CB; Hultman, P; Kono, DH Mercury-induced inflammation and autoimmunity. Biochim. Biophys. Acta, Gen. Subj., 2019., 129299.
[http://dx.doi.org/10.1016/j.bbagen.2019.02.001]
[45]
Yoo, K.Y.; Li, H.; Hwang, I.K.; Choi, J.H.; Lee, C.H.; Kwon, D.Y.; Ryu, S.Y.; Kim, Y.S.; Kang, I.J.; Shin, H.C.; Won, M.H. Zizyphus attenuates ischemic damage in the gerbil hippocampus via its antioxidant effect. J. Med. Food, 2010, 13(3), 557-563.
[http://dx.doi.org/10.1089/jmf.2009.1254] [PMID: 20521981]
[46]
Sheng, Y.; Abreu, I.A.; Cabelli, D.E.; Maroney, M.J.; Miller, A.F.; Teixeira, M.; Valentine, J.S. Superoxide dismutases and superoxide reductases. Chem. Rev., 2014, 114(7), 3854-3918.
[http://dx.doi.org/10.1021/cr4005296] [PMID: 24684599]
[47]
Al-Olayan, E.M.; El-Khadragy, M.F.; Omer, S.A.; Shata, M.T.; Kassab, R.B.; Abdel Moneim, A.E. The beneficial effect of cape gooseberry juice on carbon tetrachloride- induced neuronal damage. CNS Neurol. Disord. Drug Targets, 2016, 15(3), 344-350.
[http://dx.doi.org/10.2174/1871527314666150821112051] [PMID: 26295813]
[48]
Guizani, N.; Waly, M.I.; Singh, V.; Rahman, M.S. Nabag (Zizyphus spina-christi) extract prevents aberrant crypt foci development in colons of azoxymethane-treated rats by abrogating oxidative stress and inducing apoptosis. Asian Pac. J. Cancer Prev., 2013, 14(9), 5031-5035.
[http://dx.doi.org/10.7314/APJCP.2013.14.9.5031] [PMID: 24175771]
[49]
Glombitza, K.W.; Mahran, G.H.; Mirhom, Y.W.; Michel, K.G.; Motawi, T.K. Hypoglycemic and antihyperglycemic effects of Zizyphus spina-christi in rats. Planta Med., 1994, 60(3), 244-247.
[http://dx.doi.org/10.1055/s-2006-959468] [PMID: 8073092]
[50]
Zhu, J.T.; Choi, R.C.; Chu, G.K.; Cheung, A.W.; Gao, Q.T.; Li, J.; Jiang, Z.Y.; Dong, T.T.; Tsim, K.W. Flavonoids possess neuroprotective effects on cultured pheochromocytoma PC12 cells: a comparison of different flavonoids in activating estrogenic effect and in preventing beta-amyloid-induced cell death. J. Agric. Food Chem., 2007, 55(6), 2438-2445.
[http://dx.doi.org/10.1021/jf063299z] [PMID: 17323972]
[51]
Kumar, S.; Pandey, A.K. Chemistry and biological activities of flavonoids: an overview. ScientificWorldJournal, 2013., 2013162750.
[http://dx.doi.org/10.1155/2013/162750] [PMID: 24470791]
[52]
Yin, M.; Jiang, N.; Guo, L.; Ni, Z.; Al-Brakati, A.Y.; Othman, M.S.; Abdel Moneim, A.E.; Kassab, R.B. Oleuropein suppresses oxidative, inflammatory, and apoptotic responses following glycerol-induced acute kidney injury in rats. Life Sci., 2019., 232116634.
[http://dx.doi.org/10.1016/j.lfs.2019.116634] [PMID: 31279782]
[53]
Al-Brakati, A.Y.; Fouda, M.S.; Tharwat, A.M.; Elmahallawy, E.K.; Kassab, R.B.; Abdel Moneim, A.E. The protective efficacy of soursop fruit extract against hepatic injury associated with acetaminophen exposure is mediated through antioxidant, anti-inflammatory, and anti-apoptotic activities. Environ. Sci. Pollut. Res. Int., 2019, 26(13), 13539-13550.
[http://dx.doi.org/10.1007/s11356-019-04935-3] [PMID: 30915694]
[54]
Jaiswal, A.K. Nrf2 signaling in coordinated activation of antioxidant gene expression. Free Radic. Biol. Med., 2004, 36(10), 1199-1207.
[http://dx.doi.org/10.1016/j.freeradbiomed.2004.02.074] [PMID: 15110384]
[55]
Clark, J.E.; Foresti, R.; Sarathchandra, P.; Kaur, H.; Green, C.J.; Motterlini, R. Heme oxygenase-1-derived bilirubin ameliorates postischemic myocardial dysfunction. Am. J. Physiol. Heart Circ. Physiol., 2000, 278(2), H643-H651.
[http://dx.doi.org/10.1152/ajpheart.2000.278.2.H643] [PMID: 10666097]
[56]
Otterbein, L.E.; Choi, A.M. Heme oxygenase: colors of defense against cellular stress. Am. J. Physiol. Lung Cell. Mol. Physiol., 2000, 279(6), L1029-L1037.
[http://dx.doi.org/10.1152/ajplung.2000.279.6.L1029] [PMID: 11076792]
[57]
Liu, X.M.; Chapman, G.B.; Wang, H.; Durante, W. Adenovirus-mediated heme oxygenase-1 gene expression stimulates apoptosis in vascular smooth muscle cells. Circulation, 2002, 105(1), 79-84.
[http://dx.doi.org/10.1161/hc0102.101369] [PMID: 11772880]
[58]
So, H.; Kim, H.; Kim, Y.; Kim, E.; Pae, H.O.; Chung, H.T.; Kim, H.J.; Kwon, K.B.; Lee, K.M.; Lee, H.Y.; Moon, S.K.; Park, R. Evidence that cisplatin-induced auditory damage is attenuated by downregulation of pro-inflammatory cytokines via Nrf2/HO-1. J. Assoc. Res. Otolaryngol., 2008, 9(3), 290-306.
[http://dx.doi.org/10.1007/s10162-008-0126-y] [PMID: 18584244]
[59]
Huang, W.; Wang, Y.; Jiang, X.; Sun, Y.; Zhao, Z.; Li, S. Protective Effect of Flavonoids from Ziziphus jujuba cv. Jinsixiaozao against Acetaminophen-Induced Liver Injury by Inhibiting Oxidative Stress and Inflammation in Mice. Molecules, 2017, 22(10), E1781.
[http://dx.doi.org/10.3390/molecules22101781] [PMID: 29053632]
[60]
Zhang, Y.K.; Wu, K.C.; Klaassen, C.D. Genetic activation of Nrf2 protects against fasting-induced oxidative stress in livers of mice. PLoS One, 2013, 8(3), e59122.
[http://dx.doi.org/10.1371/journal.pone.0059122] [PMID: 23527105]

Rights & Permissions Print Cite
Article Metrics
7
3
1
1
© 2024 Bentham Science Publishers | Privacy Policy