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Current Molecular Pharmacology

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ISSN (Print): 1874-4672
ISSN (Online): 1874-4702

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Research Article

Mechanism Involved in Fortification by Berberine in CDDP-Induced Nephrotoxicity

Author(s): Vipin K. Verma, Salma Malik, Ekta Mutneja, Anil K. Sahu, Kumari Rupashi, Amit K. Dinda, Dharamvir S. Arya and Jagriti Bhatia*

Volume 13, Issue 4, 2020

Page: [342 - 352] Pages: 11

DOI: 10.2174/1874467213666200220142202

Price: $65

Abstract

Background: The activation of Nrf2/HO-1 pathway has been shown to protect against cisplatin- induced nephrotoxicity by reducing oxidative stress. Berberine (Ber), an isoquinoline alkaloid, has demonstrated antioxidant, anti-inflammatory and anti-apoptotic activities in various experimental models.

Aim: To check the effect of Ber on cisplatin-induced nephrotoxicity and to explore the involved mechanism.

Methods: Adult male Wistar rats were divided into 6 groups: Normal, cisplatin-control, treatment groups and per se group. Normal saline and Ber (20, 40 and 80 mg/kg; p.o.) was administered to rats for 10 days. A single intraperitoneal injection of cisplatin (8 mg/kg) was injected on 7th day to induced nephrotoxicity. On 10th day, rats were sacrificed, the kidney was removed and stored for the estimation of various parameters.

Results: As compared to cisplatin-control group, Ber pretreatment improved renal function system and preserved renal architecture. It also diminished oxidative stress by upregulating the expression of Nrf2/HO-1 proteins. In addition, Ber attenuated the cisplatin mediated inflammation and apoptosis. Furthermore, it also reduced the phosphorylation of p38/JNK and PARP/Beclin-1 expression in the kidney.

Conclusion: Ber attenuated renal injury by activating Nrf2/HO-1 and inhibiting JNK/p38MAPKs/ PARP/Beclin-1 expression which prevented oxidative stress, inflammation, apoptosis and autophagy in renal tissue.

Keywords: CDDP, Berberine, Nrf2/HO-1, PARP, JNK/p38 MAPK, nephrotoxicity.

Graphical Abstract

[1]
Arany, I.; Safirstein, R.L. Cisplatin nephrotoxicity. Semin. Nephrol., 2003, 23(5), 460-464.
[http://dx.doi.org/10.1016/S0270-9295(03)00089-5 ] [PMID: 13680535]
[2]
dos Santos, N.A.; Carvalho Rodrigues, M.A.; Martins, N.M.; dos Santos, A.C. Cisplatin-induced nephrotoxicity and targets of nephroprotection: an update. Arch. Toxicol., 2012, 86(8), 1233-1250.
[http://dx.doi.org/10.1007/s00204-012-0821-7 ] [PMID: 22382776]
[3]
Chevalier, R.L. The proximal tubule is the primary target of injury and progression of kidney disease: role of the glomerulotubular junction. Am. J. Physiol. Renal Physiol., 2016, 311(1), F145-F161.
[http://dx.doi.org/10.1152/ajprenal.00164.2016 ] [PMID: 27194714]
[4]
Miller, R.P.; Tadagavadi, R.K.; Ramesh, G.; Reeves, W.B. Mechanisms of Cisplatin nephrotoxicity. Toxins (Basel), 2010, 2(11), 2490-2518.
[http://dx.doi.org/10.3390/toxins2112490 ] [PMID: 22069563]
[5]
Ansari, M.A. Sinapic acid modulates Nrf2/HO-1 signaling pathway in cisplatin-induced nephrotoxicity in rats. Biomed. Pharmacother., 2017, 93, 646-653.
[http://dx.doi.org/10.1016/j.biopha.2017.06.085 ] [PMID: 28686978]
[6]
Cui, Y.; Li, C.; Zeng, C.; Li, J.; Zhu, Z.; Chen, W.; Huang, A.; Qi, X. Tongmai Yangxin pills anti-oxidative stress alleviates cisplatin-induced cardiotoxicity: Network pharmacology analysis and experimental evidence. Biomed. Pharmacother., 2018, 108, 1081-1089.
[http://dx.doi.org/10.1016/j.biopha.2018.09.095 ] [PMID: 30372808]
[7]
Li, F.; Yao, Y.; Huang, H.; Hao, H.; Ying, M. Xanthohumol attenuates cisplatin-induced nephrotoxicity through inhibiting NF-κB and activating Nrf2 signaling pathways. Int. Immunopharmacol., 2018, 61, 277-282.
[http://dx.doi.org/10.1016/j.intimp.2018.05.017 ] [PMID: 29906742]
[8]
Zheng, H.; Lan, J.; Li, J.; Lv, L. Therapeutic effect of berberine on renal ischemia-reperfusion injury in rats and its effect on Bax and Bcl-2. Exp. Ther. Med., 2018, 16(3), 2008-2012.
[http://dx.doi.org/10.3892/etm.2018.6408 ] [PMID: 30186432]
[9]
Dhanda, S.; Kaur, S.; Sandhir, R. Preventive effect of N-acetyl-L cysteine on oxidative stress and cognitive impairment in hepatic encephalopathy following bile duct ligation. Free Radic. Biol. Med., 2013, 56, 204-215.
[http://dx.doi.org/10.1016/j.freeradbiomed.2012.09.017 ] [PMID: 23044263]
[10]
Shah, N.M.; Rushworth, S.A.; Murray, M.Y.; Bowles, K.M.; MacEwan, D.J. Understanding the role of NRF2-regulated miRNAs in human malignancies. Oncotarget, 2013, 4(8), 1130-1142.
[http://dx.doi.org/10.18632/oncotarget.1181 ] [PMID: 24029073]
[11]
Bataille, A.M.; Manautou, J.E. Nrf2: a potential target for new therapeutics in liver disease. Clin. Pharmacol. Ther., 2012, 92(3), 340-348.
[http://dx.doi.org/10.1038/clpt.2012.110 ] [PMID: 22871994]
[12]
Rani, N.; Bharti, S.; Tomar, A.; Dinda, A.K.; Arya, D.S.; Bhatia, J. Inhibition of PARP activation by enalapril is crucial for its renoprotective effect in cisplatin-induced nephrotoxicity in rats. Free Radic. Res., 2016, 50(11), 1226-1236.
[http://dx.doi.org/10.1080/10715762.2016.1228923 ] [PMID: 27571604]
[13]
Alibakhshi, T.; Khodayar, M.J.; Khorsandi, L.; Rashno, M.; Zeidooni, L. Protective effects of zingerone on oxidative stress and inflammation in cisplatin-induced rat nephrotoxicity. Biomed. Pharmacother., 2018, 105, 225-232.
[http://dx.doi.org/10.1016/j.biopha.2018.05.085 ] [PMID: 29857302]
[14]
Neamatallah, T.; El-Shitany, N.A.; Abbas, A.T.; Ali, S.S.; Eid, B.G. Honey protects against cisplatin-induced hepatic and renal toxicity through inhibition of NF-κB-mediated COX-2 expression and the oxidative stress dependent BAX/Bcl-2/caspase-3 apoptotic pathway. Food Funct., 2018, 9(7), 3743-3754.
[http://dx.doi.org/10.1039/C8FO00653A ] [PMID: 29897076]
[15]
Sahu, A.K.; Verma, V.K.; Mutneja, E.; Malik, S.; Nag, T.C.; Dinda, A.K.; Arya, D.S.; Bhatia, J. Mangiferin attenuates cisplatin-induced acute kidney injury in rats mediating modulation of MAPK pathway. Mol. Cell. Biochem., 2019, 452(1-2), 141-152.
[http://dx.doi.org/10.1007/s11010-018-3420-y ] [PMID: 30083783]
[16]
Imanshahidi, M.; Hosseinzadeh, H. Pharmacological and therapeutic effects of Berberis vulgaris and its active constituent, berberine. Phytother. Res., 2008, 22(8), 999-1012.
[http://dx.doi.org/10.1002/ptr.2399 ] [PMID: 18618524]
[17]
Zhou, J.; Yu, Y.; Yang, X.; Wang, Y.; Song, Y.; Wang, Q.; Chen, Z.; Zong, S.; Fan, M.; Meng, X.; Xie, C.; Zhou, F.; Liu, H.; Wei, F. Berberine attenuates arthritis in adjuvant-induced arthritic rats associated with regulating polarization of macrophages through AMPK/NF-кB pathway. Eur. J. Pharmacol., 2019, 852, 179-188.
[http://dx.doi.org/10.1016/j.ejphar.2019.02.036 ] [PMID: 30796904]
[18]
Eissa, L.A.; Kenawy, H.I.; El-Karef, A.; Elsherbiny, N.M.; El-Mihi, K.A. Antioxidant and anti-inflammatory activities of berberine attenuate hepatic fibrosis induced by thioacetamide injection in rats. Chem. Biol. Interact., 2018, 294, 91-100.
[http://dx.doi.org/10.1016/j.cbi.2018.08.016 ] [PMID: 30138605]
[19]
Zhu, J.R.; Lu, H.D.; Guo, C.; Fang, W.R.; Zhao, H.D.; Zhou, J.S.; Wang, F.; Zhao, Y.L.; Li, Y.M.; Zhang, Y.D.; Yang, C.Q.; Sun, J.G. Berberine attenuates ischemia-reperfusion injury through inhibiting HMGB1 release and NF-κB nuclear translocation. Acta Pharmacol. Sin., 2018, 39(11), 1706-1715.
[http://dx.doi.org/10.1038/s41401-018-0160-1 ] [PMID: 30266998]
[20]
Guna, V.; Saha, L.; Bhatia, A.; Banerjee, D.; Chakrabarti, A. Anti-Oxidant and Anti-Apoptotic Effects of Berberine in Pentylenetetrazole-Induced Kindling Model in Rat. J. Epilepsy Res., 2018, 8(2), 66-73.
[http://dx.doi.org/10.14581/jer.18011 ] [PMID: 30809499]
[21]
Pirmoradi, Z.; Yadegari, M.; Moradi, A.; Khojasteh, F.; Zare Mehrjerdi, F. Effect of berberine chloride on caspase-3 dependent apoptosis and antioxidant capacity in the hippocampus of the chronic cerebral hypoperfusion rat model. Iran. J. Basic Med. Sci., 2019, 22(2), 154-159.
[PMID: 30834080]
[22]
Hassanein, E.H.M.; Shalkami, A.S.; Khalaf, M.M.; Mohamed, W.R.; Hemeida, R.A.M. The impact of Keap1/Nrf2, P38MAPK/NF-κB and Bax/Bcl2/caspase-3 signaling pathways in the protective effects of berberine against methotrexate-induced nephrotoxicity. Biomed. Pharmacother., 2019, 109, 47-56.
[http://dx.doi.org/10.1016/j.biopha.2018.10.088 ] [PMID: 30396091]
[23]
Singh, J.; Saha, L.; Singh, N.; Kumari, P.; Bhatia, A.; Chakrabarti, A. Study of nuclear factor-2 erythroid related factor-2 activator, berberine, in paclitaxel induced peripheral neuropathy pain model in rats. J. Pharm. Pharmacol., 2019, 71(5), 797-805.
[http://dx.doi.org/10.1111/jphp.13047 ] [PMID: 30536411]
[24]
Deng, Y.; Tang, K.; Chen, R.; Nie, H.; Liang, S.; Zhang, J.; Zhang, Y.; Yang, Q. Berberine attenuates hepatic oxidative stress in rats with non-alcoholic fatty liver disease via the Nrf2/ARE signalling pathway. Exp. Ther. Med., 2019, 17(3), 2091-2098.
[http://dx.doi.org/10.3892/etm.2019.7208 ] [PMID: 30867696]
[25]
Domitrović, R.; Cvijanović, O.; Pernjak-Pugel, E.; Skoda, M.; Mikelić, L.; Crnčević-Orlić, Z. Berberine exerts nephroprotective effect against cisplatin-induced kidney damage through inhibition of oxidative/nitrosative stress, inflammation, autophagy and apoptosis. Food Chem. Toxicol., 2013, 62, 397-406.
[http://dx.doi.org/10.1016/j.fct.2013.09.003 ] [PMID: 24025684]
[26]
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]
[27]
Moron, M.S.; Depierre, J.W.; Mannervik, B. Levels of glutathione, glutathione reductase and glutathione S-transferase activities in rat lung and liver. Biochim. Biophys. Acta, 1979, 582(1), 67-78.
[http://dx.doi.org/10.1016/0304-4165(79)90289-7 ] [PMID: 760819]
[28]
Marklund, S.; Marklund, G. Involvement of the superoxide anion radical in the autoxidation of pyrogallol and a convenient assay for superoxide dismutase. Eur. J. Biochem., 1974, 47(3), 469-474.
[http://dx.doi.org/10.1111/j.1432-1033.1974.tb03714.x ] [PMID: 4215654]
[29]
Bradford, M.M. A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal. Biochem., 1976, 72, 248-254.
[http://dx.doi.org/10.1016/0003-2697(76)90527-3 ] [PMID: 942051]
[30]
Verma, V.K.; Malik, S.; Narayanan, S.P.; Mutneja, E.; Sahu, A.K.; Bhatia, J.; Arya, D.S. Role of MAPK/NF-κB pathway in cardioprotective effect of Morin in isoproterenol induced myocardial injury in rats. Mol. Biol. Rep., 2019, 46(1), 1139-1148.
[http://dx.doi.org/10.1007/s11033-018-04575-9 ] [PMID: 30666500]
[31]
Zhang, L.; Gu, Y.; Li, H. Daphnetin protects against cisplatin-induced nephrotoxicity by inhibiting inflammatory and oxidative response. Int. Immunopharmacol., 2018, 65, 402-407.
[http://dx.doi.org/10.1016/j.intimp.2018.10.018]
[32]
Siddik, Z.H. Cisplatin: mode of cytotoxic action and molecular basis of resistance. Oncogene, 2003, 22(47), 7265-7279.
[http://dx.doi.org/10.1038/sj.onc.1206933 ] [PMID: 14576837]
[33]
Davis, C.A.; Nick, H.S.; Agarwal, A. Manganese superoxide dismutase attenuates Cisplatin-induced renal injury: importance of superoxide. J. Am. Soc. Nephrol., 2001, 12(12), 2683-2690.
[PMID: 11729237]
[34]
Liu, H.; Baliga, R. Cytochrome P450 2E1 null mice provide novel protection against cisplatin-induced nephrotoxicity and apoptosis. Kidney Int., 2003, 63(5), 1687-1696.
[http://dx.doi.org/10.1046/j.1523-1755.2003.00908.x ] [PMID: 12675844]
[35]
Zhang, Y.; Tao, X.; Yin, L.; Xu, L.; Xu, Y.; Qi, Y.; Han, X.; Song, S.; Zhao, Y.; Lin, Y.; Liu, K.; Peng, J. Protective effects of dioscin against cisplatin-induced nephrotoxicity via the microRNA-34a/sirtuin 1 signalling pathway. Br. J. Pharmacol., 2017, 174(15), 2512-2527.
[http://dx.doi.org/10.1111/bph.13862 ] [PMID: 28514495]
[36]
Zhao, K.; Wen, L.B. DMF attenuates cisplatin-induced kidney injury via activating Nrf2 signaling pathway and inhibiting NF-kB signaling pathway. Eur. Rev. Med. Pharmacol. Sci., 2018, 22(24), 8924-8931.
[PMID: 30575936]
[37]
Shino, Y.; Itoh, Y.; Kubota, T.; Yano, T.; Sendo, T.; Oishi, R. Role of poly(ADP-ribose)polymerase in cisplatin-induced injury in LLC-PK1 cells. Free Radic. Biol. Med., 2003, 35(8), 966-977.
[http://dx.doi.org/10.1016/S0891-5849(03)00470-2 ] [PMID: 14556861]
[38]
Kim, H.J.; Ravichandran, K.; Ozkok, A.; Wang, Q.; He, Z.; Jani, A.; Ljubanovic, D.; Douglas, I.S.; Edelstein, C.L. The water-soluble triptolide derivative PG490-88 protects against cisplatin-induced acute kidney injury. J. Pharmacol. Exp. Ther., 2014, 349(3), 518-525.
[http://dx.doi.org/10.1124/jpet.114.213769 ] [PMID: 24727856]
[39]
Malik, S.; Suchal, K.; Bhatia, J.; Khan, S.I.; Vasisth, S.; Tomar, A.; Goyal, S.; Kumar, R.; Arya, D.S.; Ojha, S.K. Therapeutic Potential and Molecular Mechanisms of Emblica officinalis Gaertn in Countering Nephrotoxicity in Rats Induced by the Chemotherapeutic Agent Cisplatin. Front. Pharmacol., 2016, 7, 350.
[http://dx.doi.org/10.3389/fphar.2016.00350 ] [PMID: 27752245]
[40]
Sahu, B.D.; Mahesh Kumar, J.; Sistla, R. Baicalein, a Bioflavonoid, Prevents Cisplatin-Induced Acute Kidney Injury by Up-Regulating Antioxidant Defenses and Down-Regulating the MAPKs and NF-κB Pathways. PLoS One, 2015, 10(7)e0134139
[http://dx.doi.org/10.1371/journal.pone.0134139 ] [PMID: 26222683]
[41]
Sadraie, S.; Kiasalari, Z.; Razavian, M.; Azimi, S.; Sedighnejad, L.; Afshin-Majd, S.; Baluchnejadmojarad, T.; Roghani, M. Berberine ameliorates lipopolysaccharide-induced learning and memory deficit in the rat: insights into underlying molecular mechanisms. Metab. Brain Dis., 2019, 34(1), 245-255.
[http://dx.doi.org/10.1007/s11011-018-0349-5 ] [PMID: 30456649]
[42]
Pattingre, S.; Levine, B. Bcl-2 inhibition of autophagy: a new route to cancer? Cancer Res., 2006, 66(6), 2885-2888.
[http://dx.doi.org/10.1158/0008-5472.CAN-05-4412 ] [PMID: 16540632]
[43]
Bolisetty, S.; Traylor, A.M.; Kim, J.; Joseph, R.; Ricart, K.; Landar, A.; Agarwal, A. Heme oxygenase-1 inhibits renal tubular macroautophagy in acute kidney injury. J. Am. Soc. Nephrol., 2010, 21(10), 1702-1712.
[http://dx.doi.org/10.1681/ASN.2010030238 ] [PMID: 20705711]

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