Dextrose Hydration May Promote Cisplatin-induced Nephrotoxicity in Rats: Gender-related Difference

Farzaneh Karimi, Sayyedehnikta Kasaei, Azar Baradaran, Farzaneh Ashrafi, Ardeshir Talebi, Zahra Lak, Mehdi Nematbakhsh


BACKGROUNDS: Cisplatin (CP) as an anticancer drug may affect the plasma glucose level while diabetic subjects are protected against CP-induced nephrotoxicity. In the current study, the role of dextrose hydration during CP therapy on CP-induced nephrotoxicity was evaluated.

METHODS: Sixty-nine male and female rats were divided into 12 groups. The rats were hydrated with 15 mL/kg vehicle or different doses of 2%, 10% and 20% dextrose before and after 7.5 mg/kg CP administration. One week later, the biochemical and kidney function markers, and histology finding were determined.

RESULTS: All the animals co-treated with CP and 20% dextrose, were dead during one week of the experiment. Administration of CP alone increased kidney tissue damage score (KTDS) and kidney weight (KW). It also elevated the blood urea nitrogen (BUN) and BUN-creatineine ratio (BUN/Cr) levels in the serum. In addition, CP decreased body weight and creatinine (Cr) clearance (ClCr) significantly in both male and female rats (p<0.05). However, 2% and 10% dextrose did not alter the mentioned parameters in male, but 10% dextrose supplement increased the serum levels of BUN, Cr and BUN/Cr ratio, KW and KTDS significantly in female rats (p<0.05).

CONCLUSION: Our data suggest that not only do not support the nephro-protective role of dextrose hydration during CP therapy, the dextrose hydration can act as risk factor to promote CP-induced nephrotoxicity in female rats. Prohibition of high carbohydrate (glucose) diet during CP therapy is recommended.

KEYWORDS: cisplatin, nephrotoxicity, dextrose, rat, gender

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Nematbakhsh M, Pezeshki Z, Eshraghi Jazi F, Mazaheri B, Moeini M, Safari T, et al. Cisplatin-induced nephrotoxicity; protective supplements and gender differences. Asian Pac J Cancer Prev. 2017; 18: 295-314, CrossRef.

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. Nephrourol Mon. 2013; 5: 818-21, CrossRef.

Eshraghi-Jazi F, Nematbakhsh M, Nasri H, Talebi A, Haghighi M, Pezeshki Z, 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: 1389-96, PMID.

Haghighi M, Nematbakhsh M, Talebi A, Nasri H, Ashrafi F, Roshanaei K, et al. The role of angiotensin II receptor 1 (AT1) blockade in cisplatin-induced nephrotoxicity in rats: gender-related differences. Renal Failure. 2012; 34: 1046-51, CrossRef.

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, CrossRef.

Mazaheri S, Nematbakhsh M, Bahadorani M, Pezeshki Z, Talebi A, Ghannadi AR, et al. Effects of fennel essential oil on cisplatininduced nephrotoxicity in ovariectomized rats. Toxicol Int. 2013; 20: 138-45, CrossRef.

Nematbakhsh M, Hajhashemi V, Ghannadi A, Talebi A, Nikahd M. Protective effects of the Morus alba L. leaf extracts on cisplatininduced nephrotoxicity in rat. Res Pharm Sci. 2013; 8: 71-7, PMID.

Nematbakhsh M, Ashrafi F, Safari T, Talebi A, Nasri H, Mortazavi M, et al. Administration of vitamin E and losartan as prophylaxes in cisplatin-induced nephrotoxicity model in rats. J Nephrol. 2012; 25: 410-7, CrossRef.

Hosseinian S, Khajavi Rad A, Hadjzadeh MA, Roshan NM, Havakhah S, Shafiee S. The protective effect of Nigella sativa against cisplatininduced nephrotoxicity in rats. Avicenna J Phytomed. 2016; 6: 44-54, PMID.

Chen WY, Hsiao CH, Chen YC, Ho CH, Wang JJ, Hsing CH, et al. Cisplatin nephrotoxicity might have a sex difference. An analysis based on women's sex hormone changes. J Cancer. 2017; 8: 3939-44, CrossRef.

Pezeshki Z, Nematbakhsh M, Nasri H, Talebi A, Pilehvarian AA, Safari T, et al. Evidence against protective role of sex hormone estrogen in Cisplatin-induced nephrotoxicity in ovarectomized rat model. Toxic Int. 2013; 20: 43-7, CrossRef.

Ghasemi M, Nematbakhsh M, Pezeshki Z, Soltani N, Moeini M, Talebi A. Nephroprotective effect of estrogen and progesterone combination on cisplatin-induced nephrotoxicity in ovariectomized female rats. Indian J Nephrol. 2016; 26: 167-75, CrossRef.

Nematbakhsh M, Pezeshki Z, Eshraghi-Jazi F, Ashrafi F, Nasri H, Talebi A, 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, CrossRef.

Egawa-Takata T, Endo H, Fujita M, Ueda Y, Miyatake T, Okuyama H, et al. Early reduction of glucose uptake after cisplatin treatment is a marker of cisplatin sensitivity in ovarian cancer. Cancer Sci. 2010; 101: 2171-8, CrossRef.

Goldstein RS, Mayor GH, Rosenbaum RW, Hook JB, Santiago JV, Bond JT. Glucose intolerance following cis-platinum treatment in rats. Toxicology. 1982; 24: 273-80, CrossRef.

Goldstein RS, Mayor GH, Gingerich RL, Hook JB, Rosenbaum RW, Bond JT. The effects of cisplatin and other divalent platinum compounds on glucose metabolism and pancreatic endocrine function. Toxicol Appl Pharmacol. 1983; 69: 432-41, CrossRef.

Najjar TA, Saad SY. Cisplatin pharmacokinetics and its nephrotoxicity in diabetic rabbits. Chemotherapy. 2001; 47: 128-35, CrossRef.

Sarangarajan R, Cacini W. Early onset of cisplatin-induced nephrotoxicity in streptozotocin-diabetic rats treated with insulin. Basic Clin Pharmacol Toxicol. 2004; 95: 66-71, CrossRef.

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. Nephrourol Mon. 2013; 5: 884-90, CrossRef.

Scott LA, Madan E, Valentovic MA. Attenuation of cisplatin nephrotoxicity by streptozotocin-induced diabetes. Fundam Appl Toxicol. 1989; 12: 530-, CrossRef.

da Silva Faria MC, Santos NA, Carvalho Rodrigues MA, Rodrigues JL, Barbosa Junior F, Santos AC. Effect of diabetes on biodistribution, nephrotoxicity and antitumor activity of cisplatin in mice. Chem-Biol Interact. 2015; 229: 119-31, CrossRef.

Duffy EA, Fitzgerald W, Boyle K, Rohatgi R. Nephrotoxicity: evidence in patients receiving cisplatin therapy. Clin J Oncol Nurs. 2018; 22: 175-83, CrossRef.

Sarangarajan R, Cacini W. Diabetes-induced protection from cisplatin nephrotoxicity is associated with impairment of energydependent uptake by renal cortex slices. Pharmacol Toxicol. 1997; 81: 197-8, CrossRef.

Portilla D, Li S, Nagothu KK, Megyesi J, Kaissling B, Schnackenberg L, et al. Metabolomic study of cisplatin-induced nephrotoxicity. Kidney Int. 2006; 69: 2194-204, CrossRef.


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