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The effect of an specific inducible NO synthase inhibitor, S-methylisothiourea hemisulfate on cisplatin-induced nephrotoxicity; gender-related differences.

Ghayyoomi M, Soltani N, Nematbakhsh M, Moslemi F, Talebi A, Shirdavani S, Razmjoo F - Adv Biomed Res (2015)

Bottom Line: Our results showed that inhibition of iNOS by SMT could make different response in male and female animals.It is concluded that decrease in NO production by SMT has a beneficial effect on reducing CP-induced nephrotoxicity in male.However, such beneficial effect was not observed in female animals.

View Article: PubMed Central - PubMed

Affiliation: Department of Physiology, Hormozgan University of Medical Sciences, Bandar Abbas, Isfahan, Iran ; Molecular Medicine Research Center, Hormozgan University of Medical Sciences, Bandar Abbas, Isfahan, Iran ; Water and Electrolytes Research Center, Isfahan University of Medical Sciences, Isfahan, Iran.

ABSTRACT

Backgrounds: It has been previously demonstrated that the increase of nitric oxide (NO) level may promote cisplatin (CP)-induced nephrotoxicity. The aim of this study was to investigate the role of inducible NO synthase (iNOS) inhibitor to prevent CP-induced nephrotoxicity.

Materials and methods: Four groups of male and four groups of female rats were treated daily with vehicle, S-methylisothiourea hemisulfate (SMT) as a selective iNOS inhibitor (5 mg/kg/twice a day), CP (2.5 mg/kg/day), and CP + SMT for 6 days. Then, all animals were sacrificed and the serum levels of creatinine (Cr), blood urea nitrogen (BUN), nitrite, and malondialdehyde (MDA) were measured. The kidney was removed immediately for histopathological study.

Results: Our results showed that inhibition of iNOS by SMT could make different response in male and female animals. SMT therapy in male animals decreased serum BUN, Cr, nitrite, and MDA levels; and it also protected kidney against CP-induced nephrotoxicity.

Conclusion: It is concluded that decrease in NO production by SMT has a beneficial effect on reducing CP-induced nephrotoxicity in male. However, such beneficial effect was not observed in female animals.

No MeSH data available.


Related in: MedlinePlus

Compression of serum levels of BUN and Cr, and Kidney weight/100 g of bodyweight (KW g/100 g BW) and kidney tissue damage score (KTDS) in male and female rats treated with saline, CP, SMT, and combination of SMT and CP (SMT+CP) (data are expressed as mean ± SEM). The symbols indicates significant difference from (*) saline, (+) SMT, or (#) CP (P < 0.05)
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Figure 1: Compression of serum levels of BUN and Cr, and Kidney weight/100 g of bodyweight (KW g/100 g BW) and kidney tissue damage score (KTDS) in male and female rats treated with saline, CP, SMT, and combination of SMT and CP (SMT+CP) (data are expressed as mean ± SEM). The symbols indicates significant difference from (*) saline, (+) SMT, or (#) CP (P < 0.05)

Mentions: Kidney weight/100 g of bodyweight (KW/100g BW) in all groups is shown in Figure 1. This ratio did not change in female CP treated animals compared with the female sham group, but there are significant differences between male CP treated and male sham groups (P < 0.05). However, treatment with SMT alone increased the ratio in female animals unlike the male group. The results also indicated that co-administration of CP and SMT increased KW/100 g BW when compared with the CP alone treated group in females (P < 0.05). This was not observed in males.


The effect of an specific inducible NO synthase inhibitor, S-methylisothiourea hemisulfate on cisplatin-induced nephrotoxicity; gender-related differences.

Ghayyoomi M, Soltani N, Nematbakhsh M, Moslemi F, Talebi A, Shirdavani S, Razmjoo F - Adv Biomed Res (2015)

Compression of serum levels of BUN and Cr, and Kidney weight/100 g of bodyweight (KW g/100 g BW) and kidney tissue damage score (KTDS) in male and female rats treated with saline, CP, SMT, and combination of SMT and CP (SMT+CP) (data are expressed as mean ± SEM). The symbols indicates significant difference from (*) saline, (+) SMT, or (#) CP (P < 0.05)
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4544122&req=5

Figure 1: Compression of serum levels of BUN and Cr, and Kidney weight/100 g of bodyweight (KW g/100 g BW) and kidney tissue damage score (KTDS) in male and female rats treated with saline, CP, SMT, and combination of SMT and CP (SMT+CP) (data are expressed as mean ± SEM). The symbols indicates significant difference from (*) saline, (+) SMT, or (#) CP (P < 0.05)
Mentions: Kidney weight/100 g of bodyweight (KW/100g BW) in all groups is shown in Figure 1. This ratio did not change in female CP treated animals compared with the female sham group, but there are significant differences between male CP treated and male sham groups (P < 0.05). However, treatment with SMT alone increased the ratio in female animals unlike the male group. The results also indicated that co-administration of CP and SMT increased KW/100 g BW when compared with the CP alone treated group in females (P < 0.05). This was not observed in males.

Bottom Line: Our results showed that inhibition of iNOS by SMT could make different response in male and female animals.It is concluded that decrease in NO production by SMT has a beneficial effect on reducing CP-induced nephrotoxicity in male.However, such beneficial effect was not observed in female animals.

View Article: PubMed Central - PubMed

Affiliation: Department of Physiology, Hormozgan University of Medical Sciences, Bandar Abbas, Isfahan, Iran ; Molecular Medicine Research Center, Hormozgan University of Medical Sciences, Bandar Abbas, Isfahan, Iran ; Water and Electrolytes Research Center, Isfahan University of Medical Sciences, Isfahan, Iran.

ABSTRACT

Backgrounds: It has been previously demonstrated that the increase of nitric oxide (NO) level may promote cisplatin (CP)-induced nephrotoxicity. The aim of this study was to investigate the role of inducible NO synthase (iNOS) inhibitor to prevent CP-induced nephrotoxicity.

Materials and methods: Four groups of male and four groups of female rats were treated daily with vehicle, S-methylisothiourea hemisulfate (SMT) as a selective iNOS inhibitor (5 mg/kg/twice a day), CP (2.5 mg/kg/day), and CP + SMT for 6 days. Then, all animals were sacrificed and the serum levels of creatinine (Cr), blood urea nitrogen (BUN), nitrite, and malondialdehyde (MDA) were measured. The kidney was removed immediately for histopathological study.

Results: Our results showed that inhibition of iNOS by SMT could make different response in male and female animals. SMT therapy in male animals decreased serum BUN, Cr, nitrite, and MDA levels; and it also protected kidney against CP-induced nephrotoxicity.

Conclusion: It is concluded that decrease in NO production by SMT has a beneficial effect on reducing CP-induced nephrotoxicity in male. However, such beneficial effect was not observed in female animals.

No MeSH data available.


Related in: MedlinePlus