Gender Difference in Cisplatin-Induced Nephrotoxicity in a Rat Model: Greater Intensity of Damage in Male Than Female

Abstract

BackgroundNephrotoxicity and hepatotoxicity are side effects of Cisplatin (CP) therapy.ObjectivesWe investigated the role of gender in CP-induced nephrotoxicity and hepatotoxicity.Materials and MethodsLow dose of CP (1 mg/kg/day; ip) was administered daily to male and female Wistar rats for 15 consecutive days. Serum creatinine (Cr), blood urea nitrogen (BUN), malondialdehyde (MDA), nitric oxide (NO) metabolite, and magnesium (Mg) levels were determined.ResultsThe percentage of weight loss and the serum levels of MDA and nitrite in male and female animals were not statistically different. However, the serum levels of BUN, Cr, Mg, and kidney MDA levels, and kidney weight and damage score were significantly greater in males than in females (P < 0.05).ConclusionsCP-induced nephrotoxicity is gender related for which the mechanisms should be determined.

Cyclosporine-A induced nephrotoxicity in male and female rats: Is zinc a suitable protective supplement?

“…The weight gain by CYC was reported before 43 . Under conditions of induced nephrotoxicity, both body weight loss and KW gain occurred [25][26][27] . Together with BUN, Cr and BUN/Cr ratio data, it seems that weight loss and KW gain are related to CYC induced nephrotoxicity, which are confirmed by pathology findings.…”

“…El-Bassossy and Eid reported that 21 days of CYC treatment in rats led to sex-related nephrotoxicity due to different responses to inflammatory factors 20 . Until now, the role of gender or sex hormones in kidney toxicity induced by other drugs, such as cisplatin and gentamicin, have been documented [22][23][24][25][26][27][28][29][30][31][32][33] , although their mechanisms have not been completely understood. In addition, the antioxidant supplements, such as zinc (Zn), have been widely used in laboratory research to protect the kidney against injury [34][35][36][37][38][39][40][41][42] .…”

Response to "Nephrotoxicity: Evidence in Patients Receiving Cisplatin Therapy"

“…Cisplatin-induced nephrotoxicity has been reported to be gender related (Aydin, Agilli, & Aydin, 2014;Nematbakhsh et al, 2013Nematbakhsh et al, , 2017Pezeshki, Maleki, Talebi, & Nematbakhsh, 2017;Pinches et al, 2012), and risk for nephrotoxicity is higher in men than in women. The kidney function marker is also altered by cisplatin (Stakisaitis et al, 2010).…”

“…The ability of supplementations to attenuate cisplatin-induced nephrotoxicity was also gender related (Eshraghi-Jazi et al, 2011;Haghighi et al, 2012;Naseem, Hassan, Alhazza, & Chibber, 2015;Zamani et al, 2016). The female sex hormone estrogen was found to aggravate cisplatininduced nephrotoxicity (Ghasemi et al, 2016;Nematbakhsh et al, , 2013. Hypomagnesemia is a well-known side effect of cisplatin, and magnesium supplementation was suggested by Duffy et al (2018); however, the protective role of magnesium against cisplatin-induced nephrotoxicity has failed in the laboratory Soltani, Nematbakhsh, Eshraghi-Jazi, Talebi, & Ashrafi, 2013).…”

Antidepressants as a New Approach for Protective Interventions of Cisplatin-Induced Nephrotoxicity

“…Cisplatin-induced nephrotoxicity is a gender dependent; greater intensity of damage in male than female [20]. Gender differences of CPinduced nephrotoxicity may be related to CP uptake by organic cation transporter-2 (OCT2); CP uptake was increased by OCT2 overexpression in male rats and was associated with increased cellular sensitivity to CP toxicity [21,22].…”