Myrtenol Protects Against Acute Kidney Injury Induced by Cisplatin in Mice

Document Type : Original paper

Authors

Research Center of Tropical and Infectious Diseases, Kerman University of Medical Sciences, Kerman, Iran.

Abstract

Background and objectives: Cisplatin is an effective anticancer drug which has some side effects such as acute kidney injury. Myrtenol, a monoterpene alcohol which is found in some plants, has various pharmacological effects including anti-inflammatory and antioxidant activities. In this study, we evaluated the nephroprotective effects of myrtenol in acute kidney injury induced by cisplatin in male mice. Methods: In this experimental in-vivo study, 35 male mice were randomly separated into 5 groups, including control, CIS (20 mg/kg cisplatin, intraperitoneally on day 1), dimethyl sulfoxide (DMSO; received cisplatin only on day 1, plus DMSO 1% on the first day, continued for 3 days), and treatment groups (received cisplatin only on day 1, plus myrtenol 25 mg/kg and 50 mg/kg intraperitoneally on the first day, continued for 3 days). The blood urea nitrogen (BUN) levels were evaluated in serum. The renal tissues were collected for evaluating malondialdehyde (MDA), superoxide dismutase (SOD), and catalase (CAT) activities; histopathological investigation was also performed. Results: Our results showed that cisplatin administration caused significant elevation in the levels of renal MDA and serum BUN; in contrast, renal SOD and CAT activities significantly reduced. Myrtenol treatment, especially 50 mg/kg for four consecutive days mitigated these alternations in serum and renal tissue. Also, the kidney’s histopathological investigations were consistent with biochemical and oxidative parameters. Conclusion: The results of our study revealed that myrtenol ameliorates acute kidney injury induced by cisplatin via oxidative stress suppression.

Keywords

Main Subjects


  • Pabla N, Dong Z. Cisplatin nephrotoxicity: mechanisms and renoprotective strategies. Kidney Int. 2008; 73(9): 994–1007.
  • Yao X, Panichpisal K, Kurtzman N, Nugent K. Cisplatin nephrotoxicity: a review. Am J Med Sci. 2007; 334(2): 115–124.
  • Sharp CN, Siskind LJ. Developing better mouse models to study cisplatin-induced kidney injury. Am J Physiol Renal Physiol. 2017; 313(4): 835–841.
  • Goudarzi M, Khodayar MJ, Hosseini Tabatabaei SMT, Ghaznavi H, Fatemi I, Mehrzadi S. Pretreatment with melatonin protects against cyclophosphamide‐induced oxidative stress and renal damage in mice. Fundam Clin Pharmacol. 2017; 31(6): 625–635.
  • Dehnamaki F, Karimi A, Pilevarian AA, Fatemi I, Hakimizadeh E, Kaeidi A, Allahtavakoli M, Rahmani MR, Khademalhosseini M, Bazmandegan G. Treatment with troxerutin protects against cisplatin-induced kidney injury in mice. Acta Chir Belg. 2019; 119(1): 31–37.
  • Kaeidi A, Rasoulian B, Hajializadeh Z, Pourkhodadad S, Rezaei M. Cisplatin toxicity reduced in human cultured renal tubular cells by oxygen pretreatment. Ren Fail. 2013; 35(10): 1382–1386.
  • Fang CY, Lou DY, Zhou LQ, Wang JC, Yang B, He QJ, Wang JJ, Weng QJ. Natural products: potential treatments for cisplatin-induced nephrotoxicity. Acta Pharmacol Sin. 2021; 42(12): 1–19.
  • Miller R, Tadagavadi R, Ramesh G, Reeves W. Mechanisms of cisplatin nephrotoxicity. Toxins (Basel). 2010; 2(11): 2490–2518.
  • Ozkok A, Edelstein CL. Pathophysiology of cisplatin-induced acute kidney injury. Biomed Res Int. 2014; Article ID 967826.
  • Tan RZ, Wang C, Deng C, Zhong X, Yan Y, Luo Y, Lan HY, He T, Wang L. Quercetin protects against cisplatin‐induced acute kidney injury by inhibiting Mincle/Syk/NF‐κB signaling maintained macrophage inflammation. Phytother Res. 2020; 34(1): 139–152.
  • Datta SC, Datta D, Mukerji B. Pharmacognostic studies on leaves of Myrtus communis the Indian Buchu of commerce. J Sci Ind Res (C). 1961; 20C: 88–91.
  • Raeiszadeh M, Esmaeili-Tarzi M, Bahrampour-Juybari K, Nematollahi-Mahani S, Pardakhty A, Nematollahi M, Mehrabani M. Evaluation the effect of Myrtus communis L. extract on several underlying mechanisms involved in wound healing: an in vitro study. S Afr J Bot. 2018; 118: 144–150.
  • Amiri K, Nasibi S, Mehrabani M, Nematollahi MH, Harandi MF. In vitro evaluation on the scolicidal effect of Myrtus communis L. and Tripleurospermum disciforme methanolic extracts. Exp Parasitol. 2019; 199: 111–115.
  • Samareh Fekri M, Mandegary A, Sharififar F, Poursalehi HR, Nematollahi MH, Izadi A, Mehdipour M, Asadi A, Samareh Fekri M. Protective effect of standardized extract of Myrtus communis (myrtle) on experimentally bleomycin-induced pulmonary fibrosis: biochemical and histopathological study. Drug Chem Toxicol. 2018; 41(4): 408–414.
  • Evstatieva L, Todorova M, Antonova D, Staneva J. Chemical composition of the essential oils of Rhodiola rosea of three different origins. Pharmacogn Mag. 2010; 6(24): 256–258.
  • Silva RO, Salvadori MS, Sousa FBM, Santos MS, Carvalho NS, Sousa DP, Gomes BS, Oliveira FA, Barbosa ALR, Freitas RM. Evaluation of the anti‐inflammatory and antinociceptive effects of myrtenol, a plant‐derived monoterpene alcohol, in mice. Flavour Fragr J. 2014; 29(3): 184–192.
  • Huang S, Tan Z, Cai J, Wang Z, Tian Y. Myrtenol improves brain damage and promotes angiogenesis in rats with cerebral infarction by activating the ERK1/2 signalling pathway. Pharm Biol. 2021; 59(1): 584–593.
  • Sepici-Dincel A, Açıkgöz Ş, Çevik C, Sengelen M, Yeşilada E. Effects of in vivo antioxidant enzyme activities of myrtle oil in normoglycaemic and alloxan diabetic rabbits. J Ethnopharmacol. 2007; 110(3): 498–503.
  • Rathinam A, Pari L, Venkatesan M, Munusamy S. Myrtenal attenuates oxidative stress and inflammation in a rat model of streptozotocin-induced diabetes. Arch Physiol Biochem. 2019; 128(1): 175–183.
  • Gomes BS, Neto BP, Lopes EM, Cunha FV, Araújo AR, Wanderley CW, Wong DV, Júnior RCP, Ribeiro RA, Sousa DP. Anti-inflammatory effect of the monoterpene myrtenol is dependent on the direct modulation of neutrophil migration and oxidative stress. Chem Biol Interact. 2017; 273: 73–81.
  • Moreira MR, Salvadori MG, de Almeida AA, de Sousa DP, Jordán J, Satyal P, de Freitas RM, de Almeida RN. Anxiolytic-like effects and mechanism of (−)-myrtenol: a monoterpene alcohol. Neurosci Lett. 2014; 579: 119–124.
  • De Britto RM, da Silva-Neto JA, Mesquita TRR, de Vasconcelos CML, de Almeida GKM, de Jesus ICG, Dos Santos PH, Souza DS, Miguel-dos-Santos R, de Sá LA. Myrtenol protects against myocardial ischemia-reperfusion injury through antioxidant and anti-apoptotic dependent mechanisms. Food Chem Toxicol. 2018; 111: 557–566.
  • Bejeshk MA, Aminizadeh AH, Jafari E, Motamedi S, Zangiabadi I, Ghasemi A, Fathi M, Nezhadi A, Akhgarandouz F, Bejeshk F, Mohammadi L, Mohammadi F, Rajizadeh MA. Myrtenol ameliorates recognition memories' impairment and anxiety-like behaviors induced by asthma by mitigating hippocampal inflammation and oxidative stress in rats. Neuroimmunomodulation. 2023; 30(1): 42–54.
  • Bejeshk M, Fekri MS, Najafipour H, Rostamzadeh F, Jafari E, Rajizadeh M, Masoumi-Ardakani Y. Anti-inflammatory and anti-remodeling effects of myrtenol in the lungs of asthmatic rats: histopathological and biochemical findings. Allergol Immunopathol (Madr). 2019; 47(2): 185–193.
  • Bazmandegan G, Fatemi I, Kaeidi A, Khademalhosseini M, Fathinejad A, Amirteimoury M. Calcium dobesilate prevents cisplatin-induced nephrotoxicity by modulating oxidative and histopathological changes in mice. Naunyn Schmiedebergs Arch Pharmacol. 2021; 394(3): 515–521.
  • Taghipour Z, Kaviani E, Kaeidi A, Shamsizadeh A, Hassanshahi J, Fatemi I. Atorvastatin attenuates D-galactose-induced hepatorenal toxicity in mice: an experimental study with histopathological evaluations. Physiol Pharmacol. 2019; 23(1): 36–43.
  • Kaeidi A, Sahamsizadeh A, Allahtavakoli M, Fatemi I, Rahmani M, Hakimizadeh E, Hassanshahi J. The effect of oleuropein on unilateral ureteral obstruction induced-kidney injury in rats: the role of oxidative stress, inflammation and apoptosis. Mol Biol Rep. 2020; 47(2): 1371–1379.
  • Kaeidi A, Taghipour Z, Allahtavakoli M, Fatemi I, Hakimizadeh E, Hassanshahi J. Ameliorating effect of troxerutin in unilateral ureteral obstruction induced renal oxidative stress, inflammation, and apoptosis in male rats. Naunyn Schmiedebergs Arch Pharmacol. 2020; 393(5): 879–888.
  • Buege JA, Aust SD. Microsomal lipid peroxidation. Methods Enzymol. 1978; 52: 302–310.
  • Mehrzadi S, Khalili H, Fatemi I, Malayeri A, Siahpoosh A, Goudarzi M. Zingerone mitigates carrageenan-induced inflammation through antioxidant and anti-inflammatory activities. Inflammation. 2021; 44(1): 186–193.
  • Hosseinzadeh A, Goudarzi M, Fatemi I, Khodayar MJ, Mehrzadi S, Khalili HR, Karimi MA. Gemfibrozil attenuates doxorubicin induced toxicity in renal tissues of male rats by reducing the oxidative insult and inflammation. Biotech Histochem. 2020; 95(7): 532–539.
  • Allameh H, Fatemi I, Malayeri AR, Nesari A, Mehrzadi S, Goudarzi M. Pretreatment with berberine protects against cisplatin-induced renal injury in male Wistar rats. Naunyn Schmiedebergs Arch Pharmacol. 2020; 393(10): 1825–1833.
  • Ateşşahín A, Çeríbaşi AO, Yuce A, Bulmus Ö, Çikim G. Role of ellagic acid against cisplatin‐induced nephrotoxicity and oxidative stress in rats. Basic Clin Pharmacol Toxicol. 2007; 100(2): 121–126.
  • Atessahin A, Yilmaz S, Karahan I, Ceribasi AO, Karaoglu A. Effects of lycopene against cisplatin-induced nephrotoxicity and oxidative stress in rats. Toxicology. 2005; 212(2–3): 116–123.
  • Chirino YI, Sánchez-González DJ, Martínez-Martínez CM, Cruz C, Pedraza-Chaverri J. Protective effects of apocynin against cisplatin-induced oxidative stress and nephrotoxicity. Toxicology. 2008; 245(1–2): 18–23.
  • Ehsani V, Amirteimoury M, Taghipour Z, Shamsizadeh A, Bazmandegan G, Rahnama A, Khajehasani F, Fatemi I. Protective effect of hydroalcoholic extract of Pistacia vera against gentamicin-induced nephrotoxicity in rats. Ren Fail. 2017; 39(1): 519–525.
  • Hakimizadeh E, Kaeidi A, Hassanshahi J, Mehrbani M, Rahmani M, Fatemi I. Ameliorating effect of pistachio hydroalcoholic extract on cisplatin-induced nephrotoxicity in mice. Res J Pharmacogn. 2021; 8(1): 73–79.
  • Xuemei L, Qiu S, Chen G, Liu M. Myrtenol alleviates oxidative stress and inflammation in diabetic pregnant rats via TLR4/MyD88/NF‐κB signaling pathway. J Biochem Mol Toxicol. 2021; Article ID 22904.
  • Viana AFSC, da Silva FV, Fernandes HDB, Oliveira IS, Braga MA, Nunes PIG, Viana DDA, de Sousa DP, Rao VS, Oliveira RDCM. Gastroprotective effect of (-)-myrtenol against ethanol-induced acute gastric lesions: possible mechanisms. J Pharm Pharmacol. 2016; 68(8): 1085–1092.
  • Un H, Ugan RA, Kose D, Bayir Y, Cadirci E, Selli J, Halici Z. A novel effect of aprepitant: protection for cisplatin-induced nephrotoxicity and hepatotoxicity. Eur J Pharmacol. 2020; Article ID 173168.
  • Amuthan A, Devi V, Shreedhara CS, Rao V, Jasphin S, Kumar N. Vernonia cinerea regenerates tubular epithelial cells in cisplatin induced nephrotoxicity in cancer bearing mice without affecting antitumor activity. J Tradit Complement Med. 2021; 11(3): 279–286.