|LETTER TO EDITOR
|Year : 2016 | Volume
| Issue : 1 | Page : 9
Comment on: Effect of pomegranate flower extract on cisplatin-induced nephrotoxicity in male rats
Amr Ahmed El-Arabey
Department of Pharmacology and Toxicology, Faculty of Pharmacy, Al Azhar University, Nasr City, Cairo, Egypt
|Date of Submission||25-Apr-2015|
|Date of Acceptance||30-Jul-2015|
|Date of Web Publication||13-Jan-2016|
Amr Ahmed El-Arabey
Department of Pharmacology and Toxicology, Faculty of Pharmacy, Al Azhar University, Nasr City, Cairo
Source of Support: None, Conflict of Interest: None
|How to cite this article:|
El-Arabey AA. Comment on: Effect of pomegranate flower extract on cisplatin-induced nephrotoxicity in male rats. Int J Prev Med 2016;7:9
I read with interest a recently published article in the "Journal of Nephropathology" by Motamedi et al., entitled "Effect of pomegranate flower extract on cisplatin-induced nephrotoxicity in male rats."  The authors have concluded that low dose of pomegranate flower extract (PFE) (25 mg/kg) showed protective effects against cisplatin (CP)-induced nephrotoxicity through its antioxidant effects. On the other hand, they did not observed the protective role of a higher dose of PFE (50 mg/kg) versus CP-induced nephrotoxicity in the same animal model. They attributed these effects to the antioxidant dose, because high doses of some antioxidants do not have a protective effect, and can exacerbate tissue damage. , Here, I would like to explain the potential mechanism may be related to this difference. The CP-induced nephrotoxicity is a gender dependent; the greater intensity of damage in male than female.  Gender differences of CP-induced nephrotoxicity may be related to CP uptake by OCT2; which has been demonstrated to be higher expressed in male than in female rats.  Thus, CP uptake was increased by OCT2 overexpression in male rats and associated with increased cellular sensitivity to CP toxicity.  A study demonstrated that OCT2 level was significantly reduced in mice after castration.  Moreover, a recent study concluded that CP therapy should be avoided when the serum testosterone (TS) level is high because TS in high concentrations (the selected doses: 50 mg/kg and 100 mg/kg) promote CP-induced nephrotoxicity in surgical castrated rats.  Furthermore, a recent study showed that the low dose of TS (10 mg/kg) protects kidneys against CP-induced nephrotoxicity in surgical castrated rats.  Subsequently, It seems the protective effect of TS on CP-induced nephrotoxicity depend on its dose. In addition, several studies concluded that the consumption of PFE increases significantly TS level in male rats.  Finally, I suggest the low dose of PFE (25 mg/kg) increase TS level closed to physiological normal level; however, the high dose of PFE (50 mg/kg) increase TS level in manner leads to increase gene expression of OCT2. Therefore, low dose of PFE showed protective effects; in contrast, the high dose of PFE exacerbate tissue damage resulting from increased CP uptake by OCT2 overexpression in male rats and associated with increased cellular sensitivity to CP toxicity.
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