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Effect of testosterone on Cisplatin-induced nephrotoxicity in surgically castrated rats.

Rostami B, Nematbakhsh M, Pezeshki Z, Talebi A, Sharifi MR, Moslemi F, Eshraghi-Jazi F, Ashrafi F - Nephrourol Mon (2014)

Bottom Line: It significantly decreased the serum and kidney levels of nitrite and serum level of TS in comparison with the control group (P < 0.05).However, coadministration of CP and low dose of TS significantly decreased the serum levels of BUN as well as Cr and KTDS (P < 0.05).Administration of high-dose TS alone increased the SMDA level, KTDS, and KW while decreased the BW significantly (P < 0.05).

View Article: PubMed Central - PubMed

Affiliation: Water and Electrolytes Research Center, Isfahan University of Medical Sciences, Isfahan, IR Iran ; Department of Physiology, Isfahan University of Medical Sciences, Isfahan, IR Iran.

ABSTRACT

Background: Cisplatin (CP) is an important antitumor drug with serious side effects such as nephrotoxicity. Estrogens can affect CP-induced nephrotoxicity; however, the role of testosterone (TS), the main male sex hormone, is not clear.

Objectives: This study aimed to investigate the effect of TS on CP-induced nephrotoxicity in castrated male rats.

Materials and methods: A total of 54 male Wistar rats were castrated and allocated into eight groups. Groups 1 through 3 respectively received 10, 50, and 100 mg/kg/wk of TS and group 4 received sesame oil for four weeks; then all four groups received 2.5 mg/kg/d CP for one week. Groups 5 through 8 received the same treatment regimen as groups 1 through 4 during first four weeks but instead of CP, they received saline for one week. Then the animals were sacrificed for biochemical and histopathologic studies.

Results: CP increased the serum levels of blood urea nitrogen (BUN), creatinine (Cr), and malondialdehyde (SMDA) as well as kidney weight (KW), bodyweight (BW) loss, and kidney tissue damage score (KTDS). It significantly decreased the serum and kidney levels of nitrite and serum level of TS in comparison with the control group (P < 0.05). However, coadministration of CP and low dose of TS significantly decreased the serum levels of BUN as well as Cr and KTDS (P < 0.05). Administration of high-dose TS alone increased the SMDA level, KTDS, and KW while decreased the BW significantly (P < 0.05).

Conclusions: It seems that testosterone in low dose, i.e. physiologic dose, protects kidneys against CP-induced nephrotoxicity; however, special care is needed in CP therapy of patients with high levels of TS.

No MeSH data available.


Related in: MedlinePlus

Measured Parameters in Positive and Negative ControlsSignificant difference between positive and negative control groups (P < 0.05). Abbreviations: BUN, blood urea nitrogen; Cr, creatinine; SN, serum nitrite; SMDA, serum malondialdehyde; TS, testosterone; KN, kidney tissue levels of nitrite; KMDA, kidney tissue levels of malondialdehyde; KW, kidney weight; ΔBW, bodyweight changes; and KTDS, kidney tissue damage score.
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fig13343: Measured Parameters in Positive and Negative ControlsSignificant difference between positive and negative control groups (P < 0.05). Abbreviations: BUN, blood urea nitrogen; Cr, creatinine; SN, serum nitrite; SMDA, serum malondialdehyde; TS, testosterone; KN, kidney tissue levels of nitrite; KMDA, kidney tissue levels of malondialdehyde; KW, kidney weight; ΔBW, bodyweight changes; and KTDS, kidney tissue damage score.

Mentions: Comparison of the positive and negative control groups (group 4 and group 8, respectively) demonstrated that in the positive control group, KW, KTDS, and serum levels of BUN, Cr, and MDA had increased while the serum TS level, serum and kidney tissue levels of nitrite, and BW had decreased significantly (P < 0.05). These data confirmed CP-induced nephrotoxicity (Figure 1).


Effect of testosterone on Cisplatin-induced nephrotoxicity in surgically castrated rats.

Rostami B, Nematbakhsh M, Pezeshki Z, Talebi A, Sharifi MR, Moslemi F, Eshraghi-Jazi F, Ashrafi F - Nephrourol Mon (2014)

Measured Parameters in Positive and Negative ControlsSignificant difference between positive and negative control groups (P < 0.05). Abbreviations: BUN, blood urea nitrogen; Cr, creatinine; SN, serum nitrite; SMDA, serum malondialdehyde; TS, testosterone; KN, kidney tissue levels of nitrite; KMDA, kidney tissue levels of malondialdehyde; KW, kidney weight; ΔBW, bodyweight changes; and KTDS, kidney tissue damage score.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4318011&req=5

fig13343: Measured Parameters in Positive and Negative ControlsSignificant difference between positive and negative control groups (P < 0.05). Abbreviations: BUN, blood urea nitrogen; Cr, creatinine; SN, serum nitrite; SMDA, serum malondialdehyde; TS, testosterone; KN, kidney tissue levels of nitrite; KMDA, kidney tissue levels of malondialdehyde; KW, kidney weight; ΔBW, bodyweight changes; and KTDS, kidney tissue damage score.
Mentions: Comparison of the positive and negative control groups (group 4 and group 8, respectively) demonstrated that in the positive control group, KW, KTDS, and serum levels of BUN, Cr, and MDA had increased while the serum TS level, serum and kidney tissue levels of nitrite, and BW had decreased significantly (P < 0.05). These data confirmed CP-induced nephrotoxicity (Figure 1).

Bottom Line: It significantly decreased the serum and kidney levels of nitrite and serum level of TS in comparison with the control group (P < 0.05).However, coadministration of CP and low dose of TS significantly decreased the serum levels of BUN as well as Cr and KTDS (P < 0.05).Administration of high-dose TS alone increased the SMDA level, KTDS, and KW while decreased the BW significantly (P < 0.05).

View Article: PubMed Central - PubMed

Affiliation: Water and Electrolytes Research Center, Isfahan University of Medical Sciences, Isfahan, IR Iran ; Department of Physiology, Isfahan University of Medical Sciences, Isfahan, IR Iran.

ABSTRACT

Background: Cisplatin (CP) is an important antitumor drug with serious side effects such as nephrotoxicity. Estrogens can affect CP-induced nephrotoxicity; however, the role of testosterone (TS), the main male sex hormone, is not clear.

Objectives: This study aimed to investigate the effect of TS on CP-induced nephrotoxicity in castrated male rats.

Materials and methods: A total of 54 male Wistar rats were castrated and allocated into eight groups. Groups 1 through 3 respectively received 10, 50, and 100 mg/kg/wk of TS and group 4 received sesame oil for four weeks; then all four groups received 2.5 mg/kg/d CP for one week. Groups 5 through 8 received the same treatment regimen as groups 1 through 4 during first four weeks but instead of CP, they received saline for one week. Then the animals were sacrificed for biochemical and histopathologic studies.

Results: CP increased the serum levels of blood urea nitrogen (BUN), creatinine (Cr), and malondialdehyde (SMDA) as well as kidney weight (KW), bodyweight (BW) loss, and kidney tissue damage score (KTDS). It significantly decreased the serum and kidney levels of nitrite and serum level of TS in comparison with the control group (P < 0.05). However, coadministration of CP and low dose of TS significantly decreased the serum levels of BUN as well as Cr and KTDS (P < 0.05). Administration of high-dose TS alone increased the SMDA level, KTDS, and KW while decreased the BW significantly (P < 0.05).

Conclusions: It seems that testosterone in low dose, i.e. physiologic dose, protects kidneys against CP-induced nephrotoxicity; however, special care is needed in CP therapy of patients with high levels of TS.

No MeSH data available.


Related in: MedlinePlus