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 Table of Contents  
Year : 2015  |  Volume : 6  |  Issue : 1  |  Page : 94

Comment on: Pomegranate flower extract does not prevent cisplatin-induced nephrotoxicity in female rats

1 Department of Nephrology, Division of Nephropathology, Isfahan University of Medical Sciences, Isfahan, Iran
2 Medical Plants Research Center, Shahrekord University of Medical Sciences, Shahrekord, Iran

Date of Submission10-May-2015
Date of Acceptance08-Aug-2015
Date of Web Publication01-Oct-2015

Correspondence Address:
Mahmoud Rafieian-Kopaei
Medical Plants Research Center, Shahrekord University of Medical Sciences, Sharekord
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/2008-7802.166504

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How to cite this article:
Nasri H, Rafieian-Kopaei M. Comment on: Pomegranate flower extract does not prevent cisplatin-induced nephrotoxicity in female rats. Int J Prev Med 2015;6:94

How to cite this URL:
Nasri H, Rafieian-Kopaei M. Comment on: Pomegranate flower extract does not prevent cisplatin-induced nephrotoxicity in female rats. Int J Prev Med [serial online] 2015 [cited 2023 Feb 8];6:94. Available from: https://www.ijpvmjournal.net/text.asp?2015/6/1/94/166504

Dear Editor,

We read with interest the recently published letter [1] which was commented on an article previously published in the "International Journal Prevention Medicine" by Jilanchi et al., entitled "Pomegranate flower extract does not prevent cisplatin-induced nephrotoxicity in female rats." The author of the commentary letter has pointed to the results of Jilanchi et al. and concluded that phytoestrogens are the cause of aggravation or negative results response of pomegranate flower extract (PFE) on nephrotoxicity induced by cisplatin (CP) in female rats. [2] Here, we would like to discuss the results of the main paper [2] and explain about the commentary letter [1] written on the results of this article.

In the main experiment Jilanchi et al. designated 23 female rats into four groups and treated as follows. Groups 1 and 2 respectively received 25 and 50 (mg/kg/day) PFE, for 9 days, and cisplatin (CP) (2.5 mg/kg) daily from day 3 on. Group 3 was treated the same as Group 1 except saline instead of PFE, and Group 4 received PFE (25 mg/kg/day) alone. In this study, CP increased the serum blood urea nitrogen, creatinine, and nitrite levels; as well as kidney tissue damage score. PFE aggravated the renal tissue damage induced by CP. [1] As it was mentioned, in his letter related this effect to phytoestrogens present in PFE. Several studies have proven that oxidative stress contributes to not only CP but also a lot of other drugs induced renal toxicity. [3],[4],[5],[6],[7],[8] In this regard, oxidative stress induces processes involved in chronic renal scaring such as inflammation, apoptosis, cell proliferation, and vascular injury. For example, mitogenesis, apoptosis of tubular and mesangial cells, and hypertrophy of tubular cells are mediated by oxidative stress. Oxidative stress induced by free radicals activates expression of the genes for inflammatory chemokines, selectin species, adhesion molecules, and pro-inflammatory cytokines. These are considered as processes closely related to vascular injury. [9] Furthermore, several studies have demonstrated that plants with antioxidant activity have positive effects in prevention and treatment of oxidative stress induced renal injury. [10],[11],[12],[13],[14] In fact various mechanisms have been considered by which reno-protection might be achieved, from them, anti-oxidative properties have been considered as one of the most important of them. [15],[16],[17]

More importantly, some phytoestrogens such as soy bean phytoestrogens have shown protective effects against oxidative stress induced renal injury. [18] Pomegranate is a potent antioxidant and therefore, other mechanisms seem to be involved in aggregative or negative effect of pomegranate in Jilanchi et al. (2014) study. [1] This possibility is discussed below:

Under certain conditions antioxidants may act as pro-oxidants and promote the oxidation of other compounds. The pro-oxidant activity of antioxidants is directly proportional to the total number of their hydroxyl groups. The pro-oxidant property of antioxidants seems to be concentration-dependent. The production of superoxide anion and lipid peroxidation is increased with increasing concentrations of flavonoid antioxidants. Furthermore, the antioxidant compounds were able to induce DNA strand breakage in a concentration-dependent manner. This effect might be explained by enhancing hydroxyl radical formation of flavonoids. The reported pro-oxidant activity has been related to the structural characteristics of these compounds. [19]

In rat liver microsomes, gossypol, quercetin, and myricetin powerfully inhibited iron-induced lipid peroxidation at low micromolar concentrations (IC 50 = 1.5 μM). However, all three compounds at 100 μM concentration increased the formation of hydroxyl radical up to eight-fold. [20] In a similar pattern, human leucocytes protection by quercetin against superoxide-induced oxidative DNA damage was ambiguous. So that quercetin at doses of 1-50 μM reduced the levels of oxidative DNA damage, however, at the high dose of 100 μM the damaging level was increased. Other studies have supported these results on quercetin in showing a pro-oxidant effect at 100 μM dose. [21] These paradoxical actions of antioxidants have been demonstrated by other antioxidant compounds. [1],[22],[23],[24],[25] Therefore, the lack of protective effect of pomegranate in CP induced nephrotoxicity seems to be the pro-oxidant activity of pomegranate extract or low dose of this plant extract. [26],[27]

  References Top

Jilanchi S, Nematbakhsh M, Mazaheri S, Talebi A, Zolfaghari B, Pezeshki Z, et al. Pomegranate flower extract does not prevent cisplatin-induced nephrotoxicity in female rats. Int J Prev Med 2014;5:1621-5.  Back to cited text no. 1
  Medknow Journal  
El-Arabey AA. Comment on: Pomegranate flower extract does not prevent cisplatin-induced nephrotoxicity in female rats. Int J Prev Med 2015;6:47.  Back to cited text no. 2
[PUBMED]  Medknow Journal  
Rafieian-Kopaei M, Nasri H. Preventive role of erythropoietin against aminoglycoside renal toxicity induced nephropathy; current knowledge and new concepts. J Renal Inj Prev 2013;2:29-30.  Back to cited text no. 3
Ghorbani A, Omidvar B, Parsi A. Protective effect of selenium on cisplatin induced nephrotoxicity: A double-blind controlled randomized clinical trial. J Nephropathol 2013;2:129-34.  Back to cited text no. 4
Nasri H. Antioxidants for prevention of gentamicin-induced nephrotoxicity. Iran J Kidney Dis 2014;8:1-2.  Back to cited text no. 5
Motamedi F, Nematbakhsh M, Monajemi R, Pezeshki Z, Talebi A, Zolfaghari B, et al. Effect of pomegranate flower extract on cisplatin-induced nephrotoxicity in rats. J Nephropathol 2014;3:133-8.  Back to cited text no. 6
Baradaran A, Nasri H, Nematbakhsh M, Rafieian-Kopaei M. Antioxidant activity and preventive effect of aqueous leaf extract of Aloe vera on gentamicin-induced nephrotoxicity in male Wistar rats. Clin Ter 2014;165:7-11.  Back to cited text no. 7
Rafieian-Kopaei M, Nasri H, Nematbakhsh M, Baradaran A, Gheissari A, Rouhi H, et al. Erythropoietin ameliorates genetamicin-induced renal toxicity: A biochemical and histopathological study. J Nephropathol 2012;1:109-16.  Back to cited text no. 8
Sugiyama H, Kashihara N, Makino H, Yamasaki Y, Ota Z. Reactive oxygen species induce apoptosis in cultured human mesangial cells. J Am Soc Nephrol 1996;7:2357-63.  Back to cited text no. 9
Tamadon MR, Baradaran A, Rafieian-Kopaei M. Antioxidant and kidney protection; differential impacts of single and whole natural antioxidants. J Renal Inj Prev 2013;3:41-2.  Back to cited text no. 10
Hajian S. Renoprotective effects of green tea. J Nephropharmacol 2013;2:2122.  Back to cited text no. 11
Nasri H, Nematbakhsh M, Rafieian-Kopaei M. Ethanolic extract of garlic for attenuation of gentamicin-induced nephrotoxicity in Wistar rats. Iran J Kidney Dis 2013;7:376-82.  Back to cited text no. 12
Rafieian-Kopaei M, Baradaran A, Rafieian M. Plants antioxidants: From laboratory to clinic. J Nephropathol 2013;2:152-3.  Back to cited text no. 13
Rafieian-Kopaei M. Medicinal plants for renal injury prevention. J Renal Inj Prev 2013;2:63-5.  Back to cited text no. 14
Kafeshani M. Ginger, micro-inflammation and kidney disease. J Renal Endocrinol 2015;1:e04.  Back to cited text no. 15
Tamadon MR, Zahmatkesh M, Beladi Mousavi SS. Administration of antioxidants in chronic kidney disease. J Nephropharmacol 2015;4:9-11.  Back to cited text no. 16
Nasri H, Ardalan MR, Rafieian-Kopaei M. Mechanistic impacts of medicinal plants in diabetic kidney disease. Iran J Public Health 2014;43:1311-3.  Back to cited text no. 17
Velasquez MT, Bhathena SJ. Dietary phytoestrogens : a0 possible role in renal disease protection. Am J Kidney Dis 2001;37:1056-68.  Back to cited text no. 18
Yen GC, Duh PD, Tsai HL, Huang SL. Pro-oxidative properties of flavonoids in human lymphocytes. Biosci Biotechnol Biochem 2003;67:1215-22.  Back to cited text no. 19
Laughton MJ, Halliwell B, Evans PJ, Hoult JR. Antioxidant and pro-oxidant actions of the plant phenolics quercetin, gossypol and myricetin. Effects on lipid peroxidation, hydroxyl radical generation and bleomycin-dependent damage to DNA. Biochem Pharmacol 1989;38:2859-65.  Back to cited text no. 20
Wilms LC, Kleinjans JC, Moonen EJ, Briedé JJ. Discriminative protection against hydroxyl and superoxide anion radicals by quercetin in human leucocytes in vitro. Toxicol In Vitro 2008;22:301-7.  Back to cited text no. 21
Nematbakhsh M, Nasri H. The effects of vitamin E and selenium on cisplatin-induced nephrotoxicity in cancer patients treated with cisplatin-based chemotherapy: A randomized, placebo-controlled study. J Res Med Sci 2013;18:626-7.  Back to cited text no. 22
[PUBMED]  Medknow Journal  
Rafieian-Kopaei M, Hosseini M, Shirzad H. Comment on : e0 ffect of pomegranate flower extract on cisplatin-induced nephrotoxicity in rats. J Nephropathol 2014;3:121-3.  Back to cited text no. 23
Nasri H. C-Phycocyanin attenuates cisplatin-induced nephrotoxicity in mice. Ren Fail 2013;35:1054-5.  Back to cited text no. 24
Nasri H, Rafieian-Kopaei M. Effect of vitamin D on insulin resistance and nephropathy in type 2 diabetes. J Res Med Sci 2014;19:581-2.  Back to cited text no. 25
[PUBMED]  Medknow Journal  
Karimi A, Moradi MT. Total phenolic compounds and in vitro antioxidant potential of crude methanol extract and the correspond fractions of Quercus brantii L. acorn. J HerbMed Pharmacol 2015;4:35-39.  Back to cited text no. 26
Nasri H, Shirzad H, Baradaran A. Rafieian-kopaei M. Antioxidant plants and diabetes mellitus. J Res Med Sci 2015; 20:491-50.  Back to cited text no. 27
  Medknow Journal  

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