The Chemoprotective Potentials of Alpha-lipoic Acid against
Cisplatin-induced Ototoxicity: A Systematic Review

Ghaidaa   Raheem   Lateef Al-Awsi; Uzma      Arshed; Anam      Arif; Andrés   Alexis   Ramírez-Coronel; Muataz   S.   Alhassan; Yasser   Fakri   Mustafa; Ferry   Fadzlul   Rahman; Rahman   S.   Zabibah; Jitendra      Gupta; Muhammad   Shahid   Iqbal; Acim   Heri   Iswanto; Bagher      Farhood
Abstract

Purpose: Ototoxicity is one of the major adverse effects of cisplatin therapy which restrict its clinical application. Alpha-lipoic acid administration may mitigate cisplatin-induced ototoxicity. In the present study, we reviewed the protective potentials of alpha-lipoic acid against the cisplatin-mediated ototoxic adverse effects.
Methods: Based on the PRISMA guideline, we performed a systematic search for the identification of all relevant studies in various electronic databases up to June 2022. According to the inclusion and exclusion criteria, the obtained articles (n=59) were screened and 13 eligible articles were finally included in the present study.
Results: The findings of in-vitro experiments showed that cisplatin treatment significantly reduced the auditory cell viability in comparison with the control group; nevertheless, the alpha-lipoic acid co-administration protected the cells against the reduction of cell viability induced by cisplatin treatment. Moreover, the in-vivo results of the auditory brainstem response (ABR) and distortion product otoacoustic emission (DPOAE) tests revealed a decrease in DPOAE and an increase in ABR threshold of cisplatin-injected animals; however, it was shown that alpha-lipoic acid co-treatment had an opposite pattern on the evaluated parameters. Other findings demonstrated that cisplatin treatment could significantly induce the biochemical and histopathological alterations in inner ear cells/tissue; in contrast, alpha-lipoic acid co-treatment ameliorated the cisplatin-mediated biochemical and histological changes.
Conclusion: The findings of audiometry, biochemical parameters, and histological evaluation showed that alpha-lipoic acid co-administration alleviates the cisplatin-induced ototoxicity. The protective role of alpha-lipoic acid against the cisplatin-induced ototoxicity can be due to different mechanisms of anti-oxidant, anti-apoptotic, anti-inflammatory activities, and regulation of cell cycle progression.
[1]
Mortezaee, K.; Narmani, A.; Salehi, M.; Bagheri, H.; Farhood, B.; Haghi-Aminjan, H.; Najafi, M. Synergic effects of nanoparticles-mediated hyperthermia in radiotherapy/chemotherapy of cancer. Life Sci.,  2021, 269, 119020.
 [http://dx.doi.org/10.1016/j.lfs.2021.119020] [PMID: 33450258]

[2]
Sheikholeslami, S.; Khodaverdian, S.; Dorri-Giv, M.; Mohammad Hosseini, S.; Souri, S.; Abedi-Firouzjah, R.; Zamani, H.; Dastranj, L.; Farhood, B. The radioprotective effects of alpha-lipoic acid on radiotherapy-induced toxicities: A systematic review. Int. Immunopharmacol.,  2021, 96, 107741.
 [http://dx.doi.org/10.1016/j.intimp.2021.107741] [PMID: 33989970]

[3]
Sheikholeslami, S.; Aryafar, T.; Abedi-Firouzjah, R.; Banaei, A.; Dorri-Giv, M.; Zamani, H.; Ataei, G.; Majdaeen, M.; Farhood, B. The role of melatonin on radiation-induced pneumonitis and lung fibrosis: A systematic review. Life Sci.,  2021, 281, 119721.
 [http://dx.doi.org/10.1016/j.lfs.2021.119721] [PMID: 34146555]

[4]
Farhood, B.; Bahreyni Toossi, M.T.; Soleymanifard, S.; Mohebbi, S.; Davenport, D. Assessment of accuracy of out of field dose calculations by TiGRT treatment planning system in radiotherapy. J. Cancer Res. Ther.,  2018, 14(3), 634-639.
 [http://dx.doi.org/10.4103/0973-1482.176423] [PMID: 29893331]

[5]
Abdi Goushbolagh, N.; Abedi Firouzjah, R.; Ebrahimnejad Gorji, K.; Khosravanipour, M.; Moradi, S.; Banaei, A. Estimation of radiation dose-reduction factor for cerium oxide nanoparticles in MRC-5 human lung fibroblastic cells and MCF-7 breast-cancer cells. Artificial Cells, Nanomed., and Biotechnology.,  2018, 46(sup3), S1215-s25.

[6]
Abdi Goushbolagh, N.; Keshavarz, M.; Zare, M.H.; Bahreyni-Toosi, M.H.; Kargar, M.; Farhood, B. Photosensitizer effects of MWCNTs-COOH particles on CT26 fibroblastic cells exposed to laser irradiation. Artif. Cells Nanomed. Biotechnol.,  2019, 47(1), 1326-1334.
 [http://dx.doi.org/10.1080/21691401.2019.1593997] [PMID: 30964347]

[7]
Najafi, M.; Hooshangi Shayesteh, M.R.; Mortezaee, K.; Farhood, B.; Haghi-Aminjan, H. The role of melatonin on doxorubicin-induced cardiotoxicity: A systematic review. Life Sci.,  2020, 241, 117173.
 [http://dx.doi.org/10.1016/j.lfs.2019.117173] [PMID: 31843530]

[8]
Nygren, P. What is cancer chemotherapy? Acta Oncol.,  2001, 40(2-3), 166-174.
 [http://dx.doi.org/10.1080/02841860151116204] [PMID: 11441929]

[9]
Hariyanti, T.; Margiana, R.; Al-Gazally, M.E.; Patra, I.; Lateef Al-Awsi, G.R.; Hameed, N.M.; Kayumova, D.; Ansari, M.J.; Torres-Criollo, L.M.; Mustafa, Y.F.; Abedi- Firouzjah, R.; Farhood, B. The protective effects of silymarin on the reproductive toxicity: A comprehensive review. Curr. Med. Chem.,  2023, 30(39), 4421-4449.
 [PMID: 36717999]

[10]
Haghi-Aminjan, H.; Farhood, B.; Rahimifard, M.; Didari, T.; Baeeri, M.; Hassani, S.; Hosseini, R.; Abdollahi, M. The protective role of melatonin in chemotherapy-induced nephrotoxicity: A systematic review of non-clinical studies. Expert Opin. Drug Metab. Toxicol.,  2018, 14(9), 937-950.
 [http://dx.doi.org/10.1080/17425255.2018.1513492] [PMID: 30118646]

[11]
Haghi-Aminjan, H.; Asghari, M.H.; Farhood, B.; Rahimifard, M.; Hashemi Goradel, N.; Abdollahi, M. The role of melatonin on chemotherapy-induced reproductive toxicity. J. Pharm. Pharmacol.,  2018, 70(3), 291-306.
 [http://dx.doi.org/10.1111/jphp.12855] [PMID: 29168173]

[12]
Hu, L.F.; Lan, H.R.; Li, X.M.; Jin, K.T. A systematic review of the potential chemoprotective effects of resveratrol on doxorubicin-induced cardiotoxicity: Focus on the antioxidant, antiapoptotic, and anti-inflammatory activities. Oxid. Med. Cell. Longev.,  2021, 2021, 1-19.
 [http://dx.doi.org/10.1155/2021/2951697] [PMID: 34471463]

[13]
Moutabian, H.; Ghahramani-Asl, R.; Mortezazadeh, T.; Laripour, R.; Narmani, A.; Zamani, H.; Ataei, G.; Bagheri, H.; Farhood, B.; Sathyapalan, T.; Sahebkar, A. The cardioprotective effects of nano-curcumin against doxorubicin-induced cardiotoxicity: A systematic review. Biofactors,  2022, 48(3), 597-610.
 [http://dx.doi.org/10.1002/biof.1823] [PMID: 35080781]

[14]
Wang, D.; Lippard, S.J. Cellular processing of platinum anticancer drugs. Nat. Rev. Drug Discov.,  2005, 4(4), 307-320.
 [http://dx.doi.org/10.1038/nrd1691] [PMID: 15789122]

[15]
Cvitkovic, E. Cumulative toxicities from cisplatin therapy and current cytoprotective measures. Cancer Treat. Rev.,  1998, 24(4), 265-281.
 [http://dx.doi.org/10.1016/S0305-7372(98)90061-5] [PMID: 9805507]

[16]
Hanigan, M.H.; Devarajan, P. Cisplatin nephrotoxicity: Molecular mechanisms. Cancer Ther.,  2003, 1, 47-61.
 [PMID: 18185852]

[17]
Santos, N.; Ferreira, R.S.; Santos, A.C.D. Overview of cisplatin-induced neurotoxicity and ototoxicity, and the protective agents. Food Chem. Toxicol.,  2020, 136, 111079.
 [http://dx.doi.org/10.1016/j.fct.2019.111079]

[18]
van den Berg, J.H.; Beijnen, J.H.; Balm, A.J.M.; Schellens, J.H.M. Future opportunities in preventing cisplatin induced ototoxicity. Cancer Treat. Rev.,  2006, 32(5), 390-397.
 [http://dx.doi.org/10.1016/j.ctrv.2006.04.011] [PMID: 16781082]

[19]
Waissbluth, S.; Peleva, E.; Daniel, S.J. Platinum-induced ototoxicity: A review of prevailing ototoxicity criteria. Eur Arch Otorhinolaryngol.,  2017, 274(3), 1187-1196.

[20]
Schaefer, S.D.; Post, J.D.; Close, L.G.; Wright, C.G. Ototoxicity of low- and moderate-dose cisplatin. Cancer,  1985, 56(8), 1934-1939.
 [http://dx.doi.org/10.1002/1097-0142(19851015)56:8<1934::AID-CNCR2820560807>3.0.CO;2-F] [PMID: 4040801]

[21]
Sheth, S.; Mukherjea, D.; Rybak, L.P.; Ramkumar, V. Mechanisms of cisplatin-induced ototoxicity and otoprotection. Front. Cell. Neurosci.,  2017, 11, 338.
 [http://dx.doi.org/10.3389/fncel.2017.00338] [PMID: 29163050]

[22]
Gentilin, E.; Simoni, E.; Candito, M.; Cazzador, D.; Astolfi, L. Cisplatin-induced ototoxicity: Updates on molecular targets. Trends Mol. Med.,  2019, 25(12), 1123-1132.
 [http://dx.doi.org/10.1016/j.molmed.2019.08.002] [PMID: 31473143]

[23]
Haghighatdoost, F.; Hariri, M. The effect of alpha-lipoic acid on inflammatory mediators: A systematic review and meta-analysis on randomized clinical trials. Eur. J. Pharmacol.,  2019, 849, 115-123.
 [http://dx.doi.org/10.1016/j.ejphar.2019.01.065] [PMID: 30721699]

[24]
Bilska, A.; Włodek, L. Lipoic acid-the drug of the future? Pharmacol. Rep.,  2005, 57(5), 570-577.
 [PMID: 16227639]

[25]
Shay, K.P.; Moreau, R.F.; Smith, E.J.; Smith, A.R.; Hagen, T.M. Alpha-lipoic acid as a dietary supplement: Molecular mechanisms and therapeutic potential. Biochim. Biophys. Acta, Gen. Subj.,  2009, 1790(10), 1149-1160.
 [http://dx.doi.org/10.1016/j.bbagen.2009.07.026] [PMID: 19664690]

[26]
Mirtaheri, E.; Pourghassem Gargari, B.; Kolahi, S.; Dehghan, P.; Asghari-Jafarabadi, M.; Hajalilou, M.; Shakiba Novin, Z.; Mesgari Abbasi, M. Effects of alpha-lipoic acid supplementation on inflammatory biomarkers and matrix metalloproteinase-3 in rheumatoid arthritis patients. J. Am. Coll. Nutr.,  2015, 34(4), 310-317.
 [http://dx.doi.org/10.1080/07315724.2014.910740] [PMID: 25751300]

[27]
Malińska, D.; Winiarska, K.; Metabolizmu, Z.R. Kwas liponowy–charakterystyka i zastosowanie w terapii* Lipoic acid: Characteristics and therapeutic application. Postepy Hig. Med. Dosw.,  2005, 59, 535-543.

[28]
Martins, V.D.; Manfredini, V.; Peralba, M.C.; Benfato, M.S. Alpha-lipoic acid modifies oxidative stress parameters in sickle cell trait subjects and sickle cell patients. Clin.. Nutr.,  2009, 28(2), 192-7.
 [http://dx.doi.org/10.1016/j.clnu.2009.01.017]

[29]
Ergür, B.U.; Çilaker Mıcılı, S.; Yilmaz, O.; Akokay, P. The effects of α-lipoic acid on aortic injury and hypertension in the rat remnant kidney (5/6 nephrectomy) model. Anatol. J. Cardiol.,  2015, 15(16), 443-449.
 [http://dx.doi.org/10.5152/akd.2014.5483] [PMID: 25430409]

[30]
Salinthone, S.; Yadav, V.; Schillace, R.V.; Bourdette, D.N.; Carr, D.W. Lipoic acid attenuates inflammation via cAMP and protein kinase A signaling. PLoS One,  2010, 5(9), e13058.
 [http://dx.doi.org/10.1371/journal.pone.0013058] [PMID: 20927401]

[31]
Ambrosi, N.; Guerrieri, D.; Caro, F.; Sanchez, F.; Haeublein, G.; Casadei, D.; Incardona, C.; Chuluyan, E. Alpha lipoic acid: A therapeutic strategy that tend to limit the action of free radicals in transplantation. Int. J. Mol. Sci.,  2018, 19(1), 102.
 [http://dx.doi.org/10.3390/ijms19010102] [PMID: 29300330]

[32]
Holmquist, L.; Stuchbury, G.; Berbaum, K.; Muscat, S.; Young, S.; Hager, K.; Engel, J.; Münch, G. Lipoic acid as a novel treatment for Alzheimer’s disease and related dementias. Pharmacol. Ther.,  2007, 113(1), 154-164.
 [http://dx.doi.org/10.1016/j.pharmthera.2006.07.001] [PMID: 16989905]

[33]
Şehirli, Ö.; Şener, E.; Çetinel, Ş.; Yüksel, M.; Gedik, N.; Şener, G. α-lipoic acid protects against renal ischaemia–reperfusion injury in rats. Clin. Exp. Pharmacol. Physiol.,  2008, 35(3), 249-255.
 [http://dx.doi.org/10.1111/j.1440-1681.2007.04810.x] [PMID: 17941895]

[34]
Ghibu, S.; Richard, C.; Vergely, C.; Zeller, M.; Cottin, Y.; Rochette, L. Antioxidant properties of an endogenous thiol: Alpha-lipoic acid, useful in the prevention of cardiovascular diseases. J. Cardiovasc. Pharmacol.,  2009, 54(5), 391-398.
 [http://dx.doi.org/10.1097/FJC.0b013e3181be7554] [PMID: 19998523]

[35]
Golbidi, S.; Badran, M.; Laher, I. Diabetes and alpha lipoic Acid. Front. Pharmacol.,  2011, 2, 69.
 [http://dx.doi.org/10.3389/fphar.2011.00069] [PMID: 22125537]

[36]
Baur, A.; Harrer, T.; Peukert, M.; Jahn, G.; Kalden, J.R.; Fleckenstein, B. Alpha-lipoic acid is an effective inhibitor of human immuno-deficiency virus (HIV-1) replication. Klin. Wochenschr.,  1991, 69(15), 722-724.
 [http://dx.doi.org/10.1007/BF01649442] [PMID: 1724477]

[37]
Moher, D.; Liberati, A.; Tetzlaff, J.; Altman, D.G. Preferred reporting items for systematic reviews and meta-analyses: The PRISMA statement. Annals Internal Med.,  2009, 151(4), 264-9.

[38]
Kim, J.; Cho, H.J.; Sagong, B.; Kim, S.J.; Lee, J.T.; So, H.S.; Lee, I.K.; Kim, U.K.; Lee, K.Y.; Choo, Y.S. Alpha-lipoic acid protects against cisplatin-induced ototoxicity via the regulation of MAPKs and proinflammatory cytokines. Biochem. Biophys. Res. Commun.,  2014, 449(2), 183-189.
 [http://dx.doi.org/10.1016/j.bbrc.2014.04.118] [PMID: 24796665]

[39]
Koo, D.Y.; Lee, S.H.; Lee, S.; Chang, J.; Jung, H.H.; Im, G.J. Comparison of the effects of lipoic acid and glutathione against cisplatin-induced ototoxicity in auditory cells. Int. J. Pediatr. Otorhinolaryngol.,  2016, 91, 30-36.
 [http://dx.doi.org/10.1016/j.ijporl.2016.10.008] [PMID: 27863638]

[40]
Kim, K.H.; Lee, B.; Kim, Y.R.; Kim, M.A.; Ryu, N.; Jung, D.J.; Kim, U.K.; Baek, J.I.; Lee, K.Y. Evaluating protective and therapeutic effects of alpha-lipoic acid on cisplatin-induced ototoxicity. Cell Death Dis.,  2018, 9(8), 827.
 [http://dx.doi.org/10.1038/s41419-018-0888-z] [PMID: 30068942]

[41]
Lee, J.; Jung, S.Y.; Yang, K.J.; Kim, Y.; Lee, D.; Lee, M.H.; Kim, D.K. α-Lipoic acid prevents against cisplatin cytotoxicity via activation of the NRF2/HO-1 antioxidant pathway. PLoS One,  2019, 14(12), e0226769.
 [http://dx.doi.org/10.1371/journal.pone.0226769] [PMID: 31877176]

[42]
Curcio, M.; Cirillo, G.; Amato, R.; Guidotti, L.; Amantea, D.; De Luca, M.; Nicoletta, F.P.; Iemma, F.; Garcia-Gil, M. Encapsulation of alpha-lipoic acid in functional hybrid liposomes: Promising tool for the reduction of cisplatin-induced ototoxicity. Pharmaceuticals,  2022, 15(4), 394.
 [http://dx.doi.org/10.3390/ph15040394] [PMID: 35455391]

[43]
Rybak, LP; Husain, K; Whitworth, C; Somani, SM Dose dependent protection by lipoic acid against cisplatin-induced ototoxicity in rats: antioxidant defense system. Toxicol Sci.,  1999, 47(2), 195-202.
 [http://dx.doi.org/10.1093/toxsci/47.2.195]

[44]
Rybak, L.P.; Somani, S. Ototoxicity. Amelioration by protective agents. Ann. N. Y. Acad. Sci.,  1999, 884, 143-151.
 [PMID: 10842591]

[45]
Rybak, L.P.; Whitworth, C.; Somani, S. Application of antioxidants and other agents to prevent cisplatin ototoxicity. Laryngoscope,  1999, 109(11), 1740-1744.
 [http://dx.doi.org/10.1097/00005537-199911000-00003] [PMID: 10569399]

[46]
Mukherjea, D.; Jajoo, S.; Whitworth, C.; Bunch, J.R.; Turner, J.G.; Rybak, L.P.; Ramkumar, V. Short interfering RNA against transient receptor potential vanilloid 1 attenuates cisplatin-induced hearing loss in the rat. J. Neurosci.,  2008, 28(49), 13056-13065.
 [http://dx.doi.org/10.1523/JNEUROSCI.1307-08.2008] [PMID: 19052196]

[47]
Altintoprak, N.; Aydin, S.; Sanli, A.; Bilmez, Z.E.; Kösemihal, E. The protective effect of intratympanic alpha lipoic acid on cisplatin-induced ototoxicity on rats. J. Int. Adv. Otol.,  2015, 10(3), 217-221.
 [http://dx.doi.org/10.5152/iao.2014.369]

[48]
Ozkul, Y.; Songu, M.; Basoglu, M.S.; Ozturkcan, S.; Katilmis, H. Evaluation of the protective effect of α-lipoic acid on cisplatin ototoxicity using distortion-product otoacoustic emission measurements: An experimental animal study. J. Craniofac. Surg.,  2014, 25(4), 1515-1518.
 [http://dx.doi.org/10.1097/SCS.0000000000000881] [PMID: 24905944]

[49]
Mukherjea, D.; Whitworth, C.A.; Nandish, S.; Dunaway, G.A.; Rybak, L.P.; Ramkumar, V. Expression of the kidney injury molecule 1 in the rat cochlea and induction by cisplatin. Neuroscience,  2006, 139(2), 733-740.
 [http://dx.doi.org/10.1016/j.neuroscience.2005.12.044] [PMID: 16464536]

[50]
Aydin, S.; Demir, M.; Oguztüzün, S.; Altintoprak, N.; Bilmez, E.; Gül, A.; Kocdogan, A.K. GSTP1 levels in cisplatin-induced rat cochlea after alpha lipoic acid and oxytocin treatment. Indian J. Otology,  2017, 23(4), 237.
 [http://dx.doi.org/10.4103/indianjotol.INDIANJOTOL_137_16]

[51]
Florea, A.M.; Büsselberg, D. Cisplatin as an anti-tumor drug: Cellular mechanisms of activity, drug resistance and induced side effects. Cancers,  2011, 3(1), 1351-1371.
 [http://dx.doi.org/10.3390/cancers3011351] [PMID: 24212665]

[52]
Rezvanfar, M.A.; Rezvanfar, M.A.; Shahverdi, A.R.; Ahmadi, A.; Baeeri, M.; Mohammadirad, A.; Abdollahi, M. Protection of cisplatin-induced spermatotoxicity, DNA damage and chromatin abnormality by selenium nano-particles. Toxicol. Appl. Pharmacol.,  2013, 266(3), 356-365.
 [http://dx.doi.org/10.1016/j.taap.2012.11.025] [PMID: 23260366]

[53]
Galluzzi, L.; Senovilla, L.; Vitale, I.; Michels, J.; Martins, I.; Kepp, O.; Castedo, M.; Kroemer, G. Molecular mechanisms of cisplatin resistance. Oncogene,  2012, 31(15), 1869-1883.
 [http://dx.doi.org/10.1038/onc.2011.384] [PMID: 21892204]

[54]
Yasui, K; Takashima, H; Miyagawa, M; Miyazawa, K; Ochiai, T; Mukaisho, K Selective accumulation of platinum and formation of platinum-DNA adducts in hepatocellular carcinoma after transarterial chemoembolization with miriplatin. Hepato. Res.,  2013, 43(10), 1093-9.
 [http://dx.doi.org/10.1111/hepr.12059]

[55]
Brown, A.; Kumar, S.; Tchounwou, P.B. Cisplatin-based chemotherapy of human cancers. J. Cancer Sci. Ther.,  2019, 11(4), 97.
 [PMID: 32148661]

[56]
Dasari, S.; Bernard Tchounwou, P. Cisplatin in cancer therapy: Molecular mechanisms of action. Eur. J. Pharmacol.,  2014, 740, 364-378.
 [http://dx.doi.org/10.1016/j.ejphar.2014.07.025] [PMID: 25058905]

[57]
Kumar, S.; Tchounwou, P.B. Molecular mechanisms of cisplatin cytotoxicity in acute promyelocytic leukemia cells. Oncotarget,  2015, 6(38), 40734-40746.
 [http://dx.doi.org/10.18632/oncotarget.5754] [PMID: 26486083]

[58]
Cepeda, V.; Fuertes, M.A.; Castilla, J.; Alonso, C.; Quevedo, C.; Pérez, J.M. Biochemical mechanisms of cisplatin cytotoxicity. Anticancer. Agents Med. Chem.,  2007, 7(1), 3-18.
 [http://dx.doi.org/10.2174/187152007779314044] [PMID: 17266502]

[59]
Fuertes, M.; Castilla, J.; Alonso, C.; Pérez, J. Cisplatin biochemical mechanism of action: from cytotoxicity to induction of cell death through interconnections between apoptotic and necrotic pathways. Curr. Med. Chem.,  2003, 10(3), 257-266.
 [http://dx.doi.org/10.2174/0929867033368484] [PMID: 12570712]

[60]
McKeage, M.J. Comparative adverse effect profiles of platinum drugs. Drug Saf.,  1995, 13(4), 228-244.
 [http://dx.doi.org/10.2165/00002018-199513040-00003] [PMID: 8573296]

[61]
Huang, S.; Xu, A.; Sun, X.; Shang, W.; Zhou, B.; Xie, Y.; Zhao, M.; Li, P.; Lu, P.; Liu, T.; Han, F. Otoprotective effects of α-lipoic acid on A/J mice with age-related hearing loss. Otol. Neurotol.,  2020, 41(6), e648-e654.
 [http://dx.doi.org/10.1097/MAO.0000000000002643]

[62]
Han, J.S.; Kim, Y.L.; Yu, H.J.; Park, J.M.; Kim, Y.; Park, S.Y. Safety and efficacy of intratympanic alpha-lipoic acid injection in a mouse model of noise-induced hearing loss. Antioxidants,  2022, 11(8)
 [http://dx.doi.org/10.3390/antiox11081423]

[63]
Conlon, B.J.; Aran, J.M.; Erre, J.P.; Smith, D.W. Attenuation of aminoglycoside-induced cochlear damage with the metabolic antioxidant α-lipoic acid. Hear. Res.,  1999, 128(1-2), 40-44.
 [http://dx.doi.org/10.1016/S0378-5955(98)00195-6] [PMID: 10082281]

[64]
Wang, A.; Hou, N.; Bao, D.; Liu, S.; Xu, T. Mechanism of alpha-lipoic acid in attenuating kanamycin-induced ototoxicity. Neural Regen. Res.,  2012, 7(35), 2793-2800.
 [PMID: 25317129]

[65]
Husain, K.; Whitworth, C.; Somani, S.M.; Rybak, L.P. Partial protection by lipoic acid against carboplantin-induced ototoxicity in rats. Biomed. Environ. Sci.,  2005, 18(3), 198-206.
 [PMID: 16131024]

[66]
Xu, A.; Shang, W.; Wang, Y.; Sun, X.; Zhou, B.; Xie, Y.; Xu, X.; Liu, T.; Han, F. ALA protects against ERS-mediated apoptosis in a cochlear cell model with low citrate synthase expression. Arch. Biochem. Biophys.,  2020, 688, 108402.
 [http://dx.doi.org/10.1016/j.abb.2020.108402] [PMID: 32418909]

[67]
Astolfi, L.; Ghiselli, S.; Guaran, V.; Chicca, M.; Simoni, E.; Olivetto, E.; Lelli, G.; Martini, A. Correlation of adverse effects of cisplatin administration in patients affected by solid tumours: A retrospective evaluation. Oncol. Rep.,  2013, 29(4), 1285-1292.
 [http://dx.doi.org/10.3892/or.2013.2279] [PMID: 23404427]

[68]
Borse, V.; Al Aameri, R.F.H.; Sheehan, K.; Sheth, S.; Kaur, T.; Mukherjea, D.; Tupal, S.; Lowy, M.; Ghosh, S.; Dhukhwa, A.; Bhatta, P.; Rybak, L.P.; Ramkumar, V. Epigallocatechin-3-gallate, a prototypic chemopreventative agent for protection against cisplatin-based ototoxicity. Cell Death Dis.,  2017, 8(7), e2921.
 [http://dx.doi.org/10.1038/cddis.2017.314] [PMID: 28703809]

[69]
Mukherjea, D.; Jajoo, S.; Kaur, T.; Sheehan, K.E.; Ramkumar, V.; Rybak, L.P. Transtympanic administration of short interfering (si)RNA for the NOX3 isoform of NADPH oxidase protects against cisplatin-induced hearing loss in the rat. Antioxid. Redox Signal.,  2010, 13(5), 589-598.
 [http://dx.doi.org/10.1089/ars.2010.3110] [PMID: 20214492]

[70]
Kim, H.J.; Lee, J.H.; Kim, S.J.; Oh, G.S.; Moon, H.D.; Kwon, K.B.; Park, C.; Park, B.H.; Lee, H.K.; Chung, S.Y.; Park, R.; So, H.S. Roles of NADPH oxidases in cisplatin-induced reactive oxygen species generation and ototoxicity. J. Neurosci.,  2010, 30(11), 3933-3946.
 [http://dx.doi.org/10.1523/JNEUROSCI.6054-09.2010] [PMID: 20237264]

[71]
Bánfi, B.; Malgrange, B.; Knisz, J.; Steger, K.; Dubois- Dauphin, M.; Krause, K.H. NOX3, a superoxide-generating NADPH oxidase of the inner ear. J. Biol. Chem.,  2004, 279(44), 46065-46072.
 [http://dx.doi.org/10.1074/jbc.M403046200] [PMID: 15326186]

[72]
Juarez, J.C.; Manuia, M.; Burnett, M.E.; Betancourt, O.; Boivin, B.; Shaw, D.E.; Tonks, N.K.; Mazar, A.P.; Doñate, F. Superoxide dismutase 1 (SOD1) is essential for H2O2 -mediated oxidation and inactivation of phosphatases in growth factor signaling. Proc. Natl. Acad. Sci. USA,  2008, 105(20), 7147-7152.
 [http://dx.doi.org/10.1073/pnas.0709451105] [PMID: 18480265]

[73]
Ma, W.; Hu, J.; Cheng, Y.; Wang, J.; Zhang, X.; Xu, M. Ginkgolide B protects against cisplatin-induced ototoxicity: Enhancement of Akt–Nrf2–HO-1 signaling and reduction of NADPH oxidase. Cancer Chemother. Pharmacol.,  2015, 75(5), 949-959.
 [http://dx.doi.org/10.1007/s00280-015-2716-9] [PMID: 25749575]

[74]
El-Beshbishy, H.A.; Bahashwan, S.A.; Aly, H.A.A.; Fakher, H.A. Abrogation of cisplatin-induced nephrotoxicity in mice by alpha lipoic acid through ameliorating oxidative stress and enhancing gene expression of antioxidant enzymes. Eur. J. Pharmacol.,  2011, 668(1-2), 278-284.
 [http://dx.doi.org/10.1016/j.ejphar.2011.06.051] [PMID: 21763304]

[75]
Werida, R.H.; Elshafiey, R.A.; Ghoneim, A.; Elzawawy, S.; Mostafa, T.M. Role of alpha-lipoic acid in counteracting paclitaxel- and doxorubicin-induced toxicities: a randomized controlled trial in breast cancer patients. Supportive Care Cancer,  2022, 30(9), 7281-7292.

[76]
He, J.; Yu, J.J.; Xu, Q.; Wang, L.; Zheng, J.Z.; Liu, L.Z.; Jiang, B.H. Downregulation of ATG14 by EGR1-MIR152 sensitizes ovarian cancer cells to cisplatin-induced apoptosis by inhibiting cyto-protective autophagy. Autophagy,  2015, 11(2), 373-384.
 [http://dx.doi.org/10.1080/15548627.2015.1009781] [PMID: 25650716]

[77]
Najafi, M.; Mortezaee, K.; Rahimifard, M.; Farhood, B.; Haghi-Aminjan, H. The role of curcumin/curcuminoids during gastric cancer chemotherapy: A systematic review of non-clinical study. Life Sci.,  2020, 257, 118051.
 [http://dx.doi.org/10.1016/j.lfs.2020.118051] [PMID: 32634426]

[78]
Mortezaee, K.; Najafi, M.; Farhood, B.; Ahmadi, A.; Potes, Y.; Shabeeb, D.; Musa, A.E. Modulation of apoptosis by melatonin for improving cancer treatment efficiency: An updated review. Life Sci.,  2019, 228, 228-241.
 [http://dx.doi.org/10.1016/j.lfs.2019.05.009] [PMID: 31077716]

[79]
Sogwagwa, N.; Davison, G.; Khan, S.; Solomon, W. P9. Correlation of radiation induced apoptosis with Bax and Bcl-2 protein expression. Physica Medica. European J. Med. Phy.,  2016, 32, 163.

[80]
Huerta, S.; Gao, X.; Dineen, S.; Kapur, P.; Saha, D.; Meyer, J. Role of p53, Bax, p21, and DNA-PKcs in radiation sensitivity of HCT-116 cells and xenografts. Surgery,  2013, 154(2), 143-151.
 [http://dx.doi.org/10.1016/j.surg.2013.03.012] [PMID: 23889944]

[81]
Werner, L.R.; Huang, S.; Francis, D.M.; Armstrong, E.A.; Ma, F.; Li, C.; Iyer, G.; Canon, J.; Harari, P.M. Small molecule inhibition of mdm2–p53 interaction augments radiation response in human tumors. Mol. Cancer Ther.,  2015, 14(9), 1994-2003.
 [http://dx.doi.org/10.1158/1535-7163.MCT-14-1056-T] [PMID: 26162687]

[82]
Csuka, O.; RemenÁr, É.; Koronczay, K.; Doleschall, Z.; NÉmeth, G. Predictive value of p53, Bcl2 and bax in the radiotherapy of head and neck cancer. Pathol. Oncol. Res.,  1997, 3(3), 204-210.
 [http://dx.doi.org/10.1007/BF02899922] [PMID: 18470731]

[83]
Maebayashi, K.; Mitsuhashi, N.; Takahashi, T.; Sakurai, H.; Niibe, H. P53 mutation decreased radiosensitivity in rat yolk sac tumor cell lines. Int. J. Radiat. Oncol. Biol. Phys.,  1999, 44(3), 677-682.
 [http://dx.doi.org/10.1016/S0360-3016(99)00025-5] [PMID: 10348299]

[84]
Sugihara, T.; Murano, H.; Nakamura, M.; Ichinohe, K.; Tanaka, K. p53-Mediated gene activation in mice at high doses of chronic low-dose-rate γ radiation. Radiat. Res.,  2010, 175(3), 328-335.
 [http://dx.doi.org/10.1667/RR2446.1] [PMID: 21388276]

[85]
Punnoose, E.A.; Leverson, J.D.; Peale, F.; Boghaert, E.R.; Belmont, L.D.; Tan, N.; Young, A.; Mitten, M.; Ingalla, E.; Darbonne, W.C.; Oleksijew, A.; Tapang, P.; Yue, P.; Oeh, J.; Lee, L.; Maiga, S.; Fairbrother, W.J.; Amiot, M.; Souers, A.J.; Sampath, D. Expression profile of BCL-2, BCL-XL, and MCL-1 predicts pharmacological response to the BCL-2 selective antagonist venetoclax in multiple myeloma models. Mol. Cancer Ther.,  2016, 15(5), 1132-1144.
 [http://dx.doi.org/10.1158/1535-7163.MCT-15-0730] [PMID: 26939706]

[86]
Haimovitz-Friedman, A.; Kolesnick, R.N.; Fuks, Z. Ceramide signaling in apoptosis. Br. Med. Bull.,  1997, 53(3), 539-553.
 [http://dx.doi.org/10.1093/oxfordjournals.bmb.a011629] [PMID: 9374036]

[87]
Kim, H.; Yoo, W.S.; Jung, J.H.; Jeong, B.K.; Woo, S.H.; Kim, J.H.; Kim, S.J. Alpha-lipoic acid ameliorates radiation-induced lacrimal gland injury through NFAT5-dependent signaling. Int. J. Mol. Sci.,  2019, 20(22), 5691.
 [http://dx.doi.org/10.3390/ijms20225691] [PMID: 31766286]

[88]
Yue, J.; López, J.M. Understanding MAPK signaling pathways in apoptosis. Int. J. Mol. Sci.,  2020, 21(7), 2346.
 [http://dx.doi.org/10.3390/ijms21072346] [PMID: 32231094]

[89]
Wu, X.Y.; Zhai, J.; Huan, X.K.; Xu, W.W.; Tian, J.; Farhood, B. A systematic review of the therapeutic potential of resveratrol during colorectal cancer chemotherapy. Mini Rev. Med. Chem.,  2023, 23(10), 1137-1152.
 [PMID: 36173048]

[90]
Oben, K.Z.; Gachuki, B.W.; Alhakeem, S.S.; McKenna, M.K.; Liang, Y.; St Clair, D.K.; Rangnekar, V.M.; Bondada, S. Radiation induced apoptosis of murine bone marrow cells is independent of Early Growth Response 1 (EGR1). PLoS One,  2017, 12(1), e0169767.
 [http://dx.doi.org/10.1371/journal.pone.0169767] [PMID: 28081176]

[91]
Komarova, E.A.; Kondratov, R.V.; Wang, K.; Christov, K.; Golovkina, T.V.; Goldblum, J.R.; Gudkov, A.V. Dual effect of p53 on radiation sensitivity in vivo: p53 promotes hematopoietic injury, but protects from gastro-intestinal syndrome in mice. Oncogene,  2004, 23(19), 3265-3271.
 [http://dx.doi.org/10.1038/sj.onc.1207494] [PMID: 15064735]

[92]
Olgun, Y.; Altun, Z.; Aktas, S.; Ercetin, P.; Kirkim, G.; Kiray, M. Molecular mechanisms of protective effect of resveratrol against cisplatinium induced ototoxicity. J. Int. Adv. Otol.,  2013, 9(2), 145.

[93]
Olgun, Y.; Kırkım, G.; Kolatan, E.; Kıray, M.; Bagrıyanık, A.; Olgun, A.; Kızmazoglu, D.C.; Ellıdokuz, H.; Serbetcıoglu, B.; Altun, Z.; Aktas, S.; Yılmaz, O.; Günerı, E.A. Friend or foe? Effect of oral resveratrol on cisplatin ototoxicity. Laryngoscope,  2014, 124(3), 760-766.
 [http://dx.doi.org/10.1002/lary.24323] [PMID: 23900991]

[94]
Freitas, M.R.D.; Figueiredo, A.A.; Brito, G.A.C.; Leitao, R.F.C.; Carvalho Junior, J.V.; Gomes Junior, R.M.; Ribeiro, R.A. The role of apoptosis in cisplatin-induced ototoxicity in rats. Rev. Bras. Otorrinolaringol.,  2009, 75(5), 745-752.
 [http://dx.doi.org/10.1590/S1808-86942009000500022] [PMID: 19893946]

[95]
Guo, X.; Bai, X.; Li, L.; Li, J.; Wang, H. Forskolin protects against cisplatin-induced ototoxicity by inhibiting apoptosis and ROS production. Biomedicine & pharmacotherapy,  2018, 99, 530-6.
 [http://dx.doi.org/10.1016/j.biopha.2018.01.080]

[96]
Rybak, L.P.; Whitworth, C.A.; Mukherjea, D.; Ramkumar, V. Mechanisms of cisplatin-induced ototoxicity and prevention. Hear. Res.,  2007, 226(1-2), 157-167.
 [http://dx.doi.org/10.1016/j.heares.2006.09.015] [PMID: 17113254]

[97]
Casares, C.; Ramírez-Camacho, R.; Trinidad, A.; Roldán, A.; Jorge, E.; García-Berrocal, J.R. Reactive oxygen species in apoptosis induced by cisplatin: Review of physiopathological mechanisms in animal models. Eur. Arch. Otorhinolaryngol.,  2012, 269(12), 2455-2459.

[98]
Callejo, A.; Sedó-Cabezón, L.; Juan, I.; Llorens, J. Cisplatin-induced ototoxicity: Effects, mechanisms and protection strategies. Toxics,  2015, 3(3), 268-293.
 [http://dx.doi.org/10.3390/toxics3030268] [PMID: 29051464]

[99]
Shi, D.; Liu, H.; Stern, J.S.; Yu, P.; Liu, S. Alpha-lipoic acid induces apoptosis in hepatoma cells via the PTEN/Akt pathway. FEBS Lett.,  2008, 582(12), 1667-1671.
 [http://dx.doi.org/10.1016/j.febslet.2008.04.021] [PMID: 18435927]

[100]
Dozio, E.; Ruscica, M.; Passafaro, L.; Dogliotti, G.; Steffani, L.; Pagani, A.; Demartini, G.; Esposti, D.; Fraschini, F.; Magni, P.; Magni, P. The natural antioxidant alpha-lipoic acid induces p27Kip1-dependent cell cycle arrest and apoptosis in MCF-7 human breast cancer cells. Eur. J. Pharmacol.,  2010, 641(1), 29-34.
 [http://dx.doi.org/10.1016/j.ejphar.2010.05.009] [PMID: 20580704]

[101]
Yue, L.; Ren, Y.; Yue, Q.; Ding, Z.; Wang, K.; Zheng, T.; Chen, G.; Chen, X.; Li, M.; Fan, L. α-lipoic acid targeting PDK1/NRF2 axis contributes to the apoptosis effect of lung cancer cells. Oxid. Med. Cell. Longev.,  2021, 2021, 1-16.
 [http://dx.doi.org/10.1155/2021/6633419] [PMID: 34211631]

[102]
Simbula, G; Columbano, A; Ledda-Columbano, GM; Sanna, L; Deidda, M; Diana, A Increased ROS generation and p53 activation in alpha-lipoic acid-induced apoptosis of hepatoma cells. Apoptosis,  2007, 12(1), 113-23.

[103]
Lee, Y.M.; Bae, S.Y.; Won, N.H.; Pyo, H.J.; Kwon, Y.J. Alpha-lipoic acid attenuates cisplatin-induced tubulointerstitial injuries through inhibition of mitochondrial bax translocation in rats. Nephron, Exp. Nephrol.,  2009, 113(4), e104-e112.
 [http://dx.doi.org/10.1159/000235754] [PMID: 19713707]

[104]
El-Sayed, E.S.M.; Mansour, A.M.; El-Sawy, W.S. Alpha lipoic acid prevents doxorubicin-induced nephrotoxicity by mitigation of oxidative stress, inflammation, and apoptosis in rats. J. Biochem. Mol. Toxicol.,  2017, 31(9), e21940.
 [http://dx.doi.org/10.1002/jbt.21940] [PMID: 28598563]

[105]
Erdem Guzel, E.; Kaya Tektemur, N.; Tektemur, A. Alpha-lipoic acid may ameliorate testicular damage by targeting dox-induced altered antioxidant parameters, mitofusin-2 and apoptotic gene expression. Andrologia,  2021, 53(3), e13990.
 [http://dx.doi.org/10.1111/and.13990] [PMID: 33529370]

[106]
Latacela, G.A.; Ramaiah, P.; Patra, I.; Jalil, A.T.; Gupta, R.; Madaminov, F.A.; Shaker Shafik, S.; Al-Gazally, M.E.; Ansari, M.J.; Kandeel, M.; Mustafa, Y.F.; Farhood, B. The radioprotective potentials of silymarin/silibinin against radiotherapy-induced toxicities: A systematic review of clinical and experimental studies. Curr. Med. Chem.,  2023, 30(33), 3775-3797.
 [PMID: 36424777]

[107]
Al-Saikhan, F.I. Anti-inflammatory potentials of fibraurea tinctoria leaves extract in experimental rats or animals. J. Pharma. Res. Int.,  2020, 32(8), 79-83.
 [http://dx.doi.org/10.9734/jpri/2020/v32i830474]

[108]
Vyas, D.; Laput, G.; Vyas, A. Chemotherapy-enhanced inflammation may lead to the failure of therapy and metastasis. OncoTargets Ther.,  2014, 7, 1015-1023.
 [http://dx.doi.org/10.2147/OTT.S60114] [PMID: 24959088]

[109]
Farhood, B.; Mortezaee, K.; Goradel, N.H.; Khanlarkhani, N.; Salehi, E.; Nashtaei, M.S.; Najafi, M.; Sahebkar, A. Curcumin as an anti-inflammatory agent: Implications to radiotherapy and chemotherapy. J. Cell. Physiol.,  2019, 234(5), 5728-5740.
 [http://dx.doi.org/10.1002/jcp.27442] [PMID: 30317564]

[110]
Moutabian, H.; Majdaeen, M.; Ghahramani-Asl, R.; Yadollahi, M.; Gharepapagh, E.; Ataei, G.; Falahatpour, Z.; Bagheri, H.; Farhood, B. A systematic review of the therapeutic effects of resveratrol in combination with 5-fluorouracil during colorectal cancer treatment: With a special focus on the oxidant, apoptotic, and anti-inflammatory activities. Cancer Cell Int.,  2022, 22(1), 142.
 [http://dx.doi.org/10.1186/s12935-022-02561-7] [PMID: 35366874]

[111]
So, H.; Kim, H.; Lee, J.H.; Park, C.; Kim, Y.; Kim, E.; Kim, J.K.; Yun, K.J.; Lee, K.M.; Lee, H.Y.; Moon, S.K.; Lim, D.J.; Park, R. Cisplatin cytotoxicity of auditory cells requires secretions of proinflammatory cytokines via activation of ERK and NF-kappaB. J. Assoc. Res. Otolaryngol.,  2007, 8(3), 338-355.
 [http://dx.doi.org/10.1007/s10162-007-0084-9] [PMID: 17516123]

[112]
Kim, S.J.; Kwak, H.J.; Kim, D.S.; Choi, H.M.; Sim, J.E.; Kim, S.H.; Um, J.Y.; Hong, S.H. Protective mechanism of Korean Red Ginseng in cisplatin-induced ototoxicity through attenuation of nuclear factor-κB and caspase-1 activation. Mol. Med. Rep.,  2015, 12(1), 315-322.
 [http://dx.doi.org/10.3892/mmr.2015.3396] [PMID: 25738645]

[113]
Levano, S.; Bodmer, D. Loss of STAT1 protects hair cells from ototoxicity through modulation of STAT3, c-Jun, Akt, and autophagy factors. Cell Death Dis.,  2015, 6(12), e2019.
 [http://dx.doi.org/10.1038/cddis.2015.362] [PMID: 26673664]

[114]
Sethi, G.; Tergaonkar, V. Potential pharmacological control of the NF-κB pathway. Trends Pharmacol. Sci.,  2009, 30(6), 313-321.
 [http://dx.doi.org/10.1016/j.tips.2009.03.004] [PMID: 19446347]

[115]
Nafees, S.; Rashid, S.; Ali, N.; Hasan, S.K.; Sultana, S. Rutin ameliorates cyclophosphamide induced oxidative stress and inflammation in Wistar rats: Role of NFκB/MAPK pathway. Chem. Biol. Interact.,  2015, 231, 98-107.
 [http://dx.doi.org/10.1016/j.cbi.2015.02.021] [PMID: 25753322]

[116]
Kandemir, F.M.; Kucukler, S.; Caglayan, C.; Gur, C.; Batil, A.A.; Gülçin, İ. Therapeutic effects of silymarin and naringin on methotrexate-induced nephrotoxicity in rats: Biochemical evaluation of anti-inflammatory, antiapoptotic, and antiautophagic properties. J. Food Biochem.,  2017, 41(5), e12398.
 [http://dx.doi.org/10.1111/jfbc.12398]

[117]
Kaur, T.; Mukherjea, D.; Sheehan, K.; Jajoo, S.; Rybak, L.P.; Ramkumar, V. Short interfering RNA against STAT1 attenuates cisplatin-induced ototoxicity in the rat by suppressing inflammation. Cell Death Dis.,  2011, 2(7), e180.
 [http://dx.doi.org/10.1038/cddis.2011.63] [PMID: 21776018]

[118]
Previati, M.; Lanzoni, I.; Astolfi, L.; Fagioli, F.; Vecchiati, G.; Pagnoni, A.; Martini, A.; Capitani, S. Cisplatin cytotoxicity in organ of corti-derived immortalized cells. J. Cell. Biochem.,  2007, 101(5), 1185-1197.
 [http://dx.doi.org/10.1002/jcb.21239] [PMID: 17243113]

[119]
Deveci, H.A.; Akyuva, Y.; Nur, G.; Nazıroğlu, M. Alpha lipoic acid attenuates hypoxia-induced apoptosis, inflammation and mitochondrial oxidative stress via inhibition of TRPA1 channel in human glioblastoma cell line. Biomed.  Pharmacother.,  2019, 111, 292-304.
 [http://dx.doi.org/10.1016/j.biopha.2018.12.077]

[120]
Rahimifard, M.; Navaei-Nigjeh, M.; Baeeri, M.; Maqbool, F.; Abdollahi, M. Multiple protective mechanisms of alpha-lipoic acid in oxidation, apoptosis and inflammation against hydrogen peroxide induced toxicity in human lymphocytes. Mol. Cell. Biochem.,  2015, 403(1-2), 179-186.
 [http://dx.doi.org/10.1007/s11010-015-2348-8] [PMID: 25673508]

[121]
Azmoonfar, R.; Amini, P.; Yahyapour, R.; Rezaeyan, A.; Tavassoli, A.; Motevaseli, E.; Khodamoradi, E.; Shabeeb, D.; Musa, A.E.; Najafi, M. Mitigation of radiation-induced pneumonitis and lung fibrosis using alpha-lipoic acid and resveratrol. Antiinflamm. Antiallergy Agents Med. Chem.,  2020, 19(2), 149-157.
 [http://dx.doi.org/10.2174/1871523018666190319144020] [PMID: 30892165]

[122]
Farhood, B.; Hassanzadeh, G.; Amini, P.; Shabeeb, D.; Musa, A.E.; Khodamoradi, E.; Mohseni, M.; Aliasgharzadeh, A.; Moradi, H.; Najafi, M. Mitigation of radiation-induced gastrointestinal system injury using resveratrol or alpha-lipoic acid: A pilot histopathological study. Antiinflamm. Antiallergy Agents Med. Chem.,  2020, 19(4), 413-424.
 [http://dx.doi.org/10.2174/1871523018666191111124028] [PMID: 31713500]

[123]
Yahyapour, R.; Amini, P.; Saffar, H.; Motevaseli, E.; Farhood, B.; Pooladvand, V.; Shabeeb, D.; Musa, A.E.; Najafi, M. Protective effect of metformin, resveratrol and alpha-lipoic acid on radiation-induced pneumonitis and fibrosis: A histopathological study. Curr. Drug Res. Rev.,  2019, 11(2), 111-117.
 [http://dx.doi.org/10.2174/2589977511666191018180758] [PMID: 31875783]

[124]
Li, G.; Fu, J.; Zhao, Y.; Ji, K.; Luan, T.; Zang, B. Alpha-lipoic acid exerts anti-inflammatory effects on lipopolysaccharide-stimulated rat mesangial cells via inhibition of nuclear factor kappa B (NF-κB) signaling pathway. Inflammation,  2015, 38(2), 510-519.
 [http://dx.doi.org/10.1007/s10753-014-9957-3] [PMID: 24962643]

[125]
Alanazi, A.M.; Fadda, L.; Alhusaini, A.; Ahmad, R.; Hasan, I.H.; Mahmoud, A.M. Liposomal resveratrol and/or carvedilol attenuate doxorubicin-induced cardiotoxicity by modulating inflammation, oxidative stress and S100A1 in rats. Antioxidants,  2020, 9(2), 159.

[126]
Mortezaee, K.; Najafi, M.; Farhood, B.; Ahmadi, A.; Shabeeb, D.; Musa, A.E. Resveratrol as an adjuvant for normal tissues protection and tumor sensitization. Curr. Cancer Drug Targets,  2020, 20(2), 130-145.
 [http://dx.doi.org/10.2174/1568009619666191019143539] [PMID: 31738153]

[127]
Alarcón de la Lastra, C.; Villegas, I. Resveratrol as an anti-inflammatory and anti-aging agent: Mechanisms and clinical implications. Mol. Nutr. Food Res.,  2005, 49(5), 405-430.
 [http://dx.doi.org/10.1002/mnfr.200500022] [PMID: 15832402]

[128]
Udenigwe, C.C.; Ramprasath, V.R.; Aluko, R.E.; Jones, P.J.H. Potential of resveratrol in anticancer and anti-inflammatory therapy. Nutr. Rev.,  2008, 66(8), 445-454.
 [http://dx.doi.org/10.1111/j.1753-4887.2008.00076.x] [PMID: 18667005]

[129]
de Sá Coutinho, D.; Pacheco, M.; Frozza, R.; Bernardi, A. Anti-inflammatory effects of resveratrol: Mechanistic insights. Int. J. Mol. Sci.,  2018, 19(6), 1812.
 [http://dx.doi.org/10.3390/ijms19061812] [PMID: 29925765]

[130]
Das, S.; Das, D. Anti-inflammatory responses of resveratrol. Inflamm. Allergy Drug Targets,  2007, 6(3), 168-173.
 [http://dx.doi.org/10.2174/187152807781696464] [PMID: 17897053]

[131]
Tripathy, J.; Chowdhury, A.R.; Prusty, M.; Muduli, K.; Priyadarshini, N.; Reddy, K.S.; Banerjee, B.; Elangovan, S. α-Lipoic acid prevents the ionizing radiation-induced epithelial-mesenchymal transition and enhances the radiosensitivity in breast cancer cells. Eur. J. Pharmacol.,  2020, 871, 172938.
 [http://dx.doi.org/10.1016/j.ejphar.2020.172938] [PMID: 31958458]

[132]
Choi, H.S.; Kim, J.H.; Jang, S.J.; Yun, J.W.; Kang, K.M.; Jeong, H.; Ha, I.B.; Jeong, B.K. Synergistic tumoricidal effects of alpha-lipoic acid and radiotherapy on human breast cancer cells via HMGB1. Cancer Res. Treat.,  2021, 53(3), 685-694.
 [http://dx.doi.org/10.4143/crt.2020.1015] [PMID: 33321563]

[133]
Puchsaka, P.; Chaotham, C.; Chanvorachote, P. α-Lipoic acid sensitizes lung cancer cells to chemotherapeutic agents and anoikis via integrin β1/β3 downregulation. Int. J. Oncol.,  2016, 49(4), 1445-1456.
 [http://dx.doi.org/10.3892/ijo.2016.3624] [PMID: 27431988]

[134]
Nur, G.; Nazıroğlu, M.; Deveci, H.A. Synergic prooxidant, apoptotic and TRPV1 channel activator effects of alpha-lipoic acid and cisplatin in MCF-7 breast cancer cells. J. Recept. Signal Transduct. Res.,  2017, 37(6), 569-577.
 [http://dx.doi.org/10.1080/10799893.2017.1369121] [PMID: 28849985]

[135]
Ramachandran, L.; Nair, C.K.K. Therapeutic potentials of silver nanoparticle complex of α-lipoic acid. Nanomater. Nanotechnol.,  2011, 1, 14.
 [http://dx.doi.org/10.5772/50956]

[136]
McConnell, D.; McGreevy, J.; Williams, M.; Litofsky, N. Do anti-oxidants vitamin D3, melatonin, and alpha-lipoic acid have synergistic effects with temozolomide on cultured glioblastoma cells? Medicines,  2018, 5(2), 58.
 [http://dx.doi.org/10.3390/medicines5020058] [PMID: 29925764]
Cite As
Current Medicinal Chemistry

The Chemoprotective Potentials of Alpha-lipoic Acid against Cisplatin-induced Ototoxicity: A Systematic Review

Abstract
