Sir,
I read the recently published interesting and well-designed article in the “Ren Fail,” by Boroushaki et al., entitled “Protective effect of pomegranate seed oil against cisplatin-induced nephrotoxicity in rat.”Citation1 The authors concluded that pomegranate seed oil has a protective effect for the prevention of cisplatin (CP)-induced renal dysfunction and oxidative damage. This finding, in general may not be an absolute result, and the result could be altered in different conditions. The purpose of this letter is to mention some other parameters that possibly affect the protective effect of pomegranate seed oil or other herbal or non-herbal antioxidants in CP-induced nephrotoxicity. The first important parameter is gender, because CP acts gender dependently. The pomegranate flower extract was used on CP-induced nephrotoxicity, and different results were obtained in male and female.Citation2,Citation3 It is reported that low dose of pomegranate flower extract (25 mg/kg) plays a protective role against CP-induced renal toxicity in male rats,Citation3 but such observation was not seen in female.Citation2 Also, pomegranate flower extract not only did not ameliorate CP-induced nephrotoxicity in female, but also aggravated renal tissue damage.Citation2,Citation3 CP is known as a proper chemotherapeutic drug in clinic, which is accompanied with nephrotoxicityCitation4,Citation5 and hypomagnesemia.Citation6 Previously, it was demonstrated that CP-induced nephrotoxicity is gender relatedCitation7,Citation8 and some supplementations, such as l-arginine or angiotensin II type 1 receptor inhibitor (losartan)Citation9,Citation10 have shown different protective effect against CP-induced nephrotoxicity in male and female. Surprisingly, the renoprotective effect of losartan and l-arginine did not observed in female as it was found for pomegranate flower extract, and the possible role of female sex hormone was highlighted. However, it is revealed that estrogen itself did not ameliorate CP-induced kidney injury, and more kidney tissue damage by CP was seen as estradiol level was increased.Citation11 In addition, estrogen in pharmacological doses may abolish the protective effects of vitamin E, vitamin C or losartan against CP-induced kidney injury.Citation12 Therefore, to the best of our knowledge, it seems that gender and sex hormones are extremely important, and the results obtained by Boroushaki et al. study may be reversed in female, and it is of high importance to report the serum levels of estradiol when female were selected for investigation of CP-induced nephrotoxicity.
Another parameter is the dose of CP. CP was used as single doseCitation13–18 as well as divided dosesCitation12,Citation19–21 for 5–10 days of investigation, and based on published data, the nephroprotective effect of supplementations was related to the study protocols. In Boroushaki et al. study, single dose of CP (8 mg/kg) was used, so according to some studies the results would be different if divided dose is used.Citation12–21
In this regard, to obtain a consistent clinical suggestion for pomegranate seed oil as supplementation in CP therapy, more studies related to the dose response of pomegranate seed oil, gender effect, sex hormone and dose of CP could be developed. For CP, the divided dose is suggested as in clinic CP treatment is time course treatment.
Declaration of interest
The author declare no conflict of interest.
References
- Boroushaki MT, Rajabian A, Farzadnia M, et al. Protective effect of pomegranate seed oil against cisplatin-induced nephrotoxicity in rat. Ren Fail. 2015;37:1338–1343.
- Jilanchi S, Nematbakhsh M, Mazaheri S, et al. Pomegranate flower extract does not prevent cisplatin-induced nephrotoxicity in female rats. Int J Prev Med. 2014;5:1621–1625.
- Motamedi F, Nematbakhsh M, Monajemi R, et al. Effect of pomegranate flower extract on cisplatin-induced nephrotoxicity in rats. J Nephropathol. 2014;3:133–138.
- Chirino YI, Pedraza-Chaverri J. Role of oxidative and nitrosative stress in cisplatin-induced nephrotoxicity. Exp Toxicol Pathol. 2009;61:223–242.
- Pabla N, Dong Z. Cisplatin nephrotoxicity: Mechanisms and renoprotective strategies. Kidney Int. 2008;73:994–1007.
- Lajer H, Kristensen M, Hansen H, et al. Magnesium depletion enhances cisplatin-induced nephrotoxicity. Cancer Chemother Pharmacol. 2005;56:535–542.
- Nematbakhsh M, Ebrahimian S, Tooyserkani M, Eshraghi-Jazi F, Talebi A, Ashrafi F. Gender difference in cisplatin-induced nephrotoxicity in a rat model: Greater intensity of damage in male than female. Nephro-Urol. 2013;5: 818–821.
- Jilanchi S, Nematbakhsh M, Bahadorani M, et al. Vitamin E is a nephroprotectant agent in male but not in female in a model of Cisplatin-induced nephrotoxicity. ISRN Nephrol. 2013;2013:280395.
- Eshraghi-Jazi F, Nematbakhsh M, Nasri H, et al. The protective role of endogenous nitric oxide donor (L-arginine) in cisplatin-induced nephrotoxicity: Gender related differences in rat model. J Res Med Sci. 2011;16:1389–1396.
- Haghighi M, Nematbakhsh M, Talebi A, et al. The role of angiotensin II receptor 1 (AT1) blockade in cisplatin-induced nephrotoxicity in rats: Gender-related differences. Ren Fail. 2012;34:1046–1051.
- Pezeshki Z, Nematbakhsh M, Nasri H, et al. Evidence against protective role of sex hormone estrogen in Cisplatin-induced nephrotoxicity in ovarectomized rat model. Toxicol Int. 2013;20:43–47.
- Nematbakhsh M, Pezeshki Z, Eshraghi-Jazi F, et al. Vitamin E, vitamin C, or losartan is not nephroprotectant against cisplatin-induced nephrotoxicity in presence of estrogen in ovariectomized rat model. Int J Nephrol. 2012;2012:284896.
- Ashrafi F, Haghshenas S, Nematbakhsh M, et al. The role of magnesium supplementation in cisplatin-induced nephrotoxicity in a rat model: No nephroprotectant effect. Int J Preventive Med. 2012;3:637–643.
- Mazaheri S, Nematbakhsh M, Bahadorani M, et al. Effects of fennel essential oil on cisplatin-induced nephrotoxicity in ovariectomized rats. Toxicol Int. 2013;20:138–145.
- Eshraghi-Jazi F, Nematbakhsh M, Pezeshki Z, et al. Sex differences in protective effect of recombinant human erythropoietin against cisplatin-induced nephrotoxicity in rats. Iran J Kidney Dis. 2013;7:383–389.
- Nematbakhsh M, Pezeshki Z. Sex-related difference in nitric oxide metabolites levels after nephroprotectant supplementation administration against cisplatin-induced nephrotoxicity in wistar rat model: The role of vitamin E, erythropoietin, or N-acetylcysteine. ISRN Nephrol. 2013;2013:612675.
- Ashrafi F, Nematbakhsh M, Safari T, et al. A combination of vitamin C and losartan for cisplatin-induced nephrotoxicity in rats. Iran J Kidney Dis. 2012;6:361–365.
- Nematbakhsh M, Ashrafi F, Safari T, et al. Administration of vitamin E and losartan as prophylaxes in cisplatin-induced nephrotoxicity model in rats. J Nephrol. 2012;25:410–417.
- Soltani N, Nematbakhsh M, Eshraghi-Jazi F, Talebi A, Ashrafi F. Effect of oral administration of magnesium on cisplatin-induced nephrotoxicity in normal and streptozocin-induced diabetic rats. Nephro-Urol. 2013;5:884–890.
- Rastghalam R, Nematbakhsh M, Bahadorani M, et al. Angiotensin type-1 receptor blockade may not protect kidney against cisplatin-induced nephrotoxicity in rats. ISRN Nephrol. 2014;2014:479645.
- Moslemi F, Nematbakhsh M, Eshraghi-Jazi F, et al. Inhibition of nitric oxide synthase by L-NAME promotes cisplatin-induced nephrotoxicity in male rats. ISRN Toxicol. 2013;2013:242345.