Toxicology International (Formerly Indian Journal of Toxicology)

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Modulation of Adriamycin-Induced Hepatotoxicity and Genotoxicity by Selective Inhibition of Phosphodiesterase-5 with Sildenafil in Wistar Rats


Affiliations
1 Department of Biochemistry, Bowen University, Iwo, Osun State, Nigeria
2 Department of Veterinary Anatomy, University of Ibadan, Ibadan, Nigeria
3 Department of Pharmacology, School of Medical Sciences, University of Cape Coast, Cape Coast, Ghana
     

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This study investigated the effect of selective inhibition of phosphodiesterase-5 on hepatotoxicity and genotoxicity induced by adriamycin in rats. Thirty male Wistar rats (150 - 250 g) were randomly assigned into six groups of 5 rats/group. Negative, positive and sildenafil controls received physiological saline (10 ml/kg, p.o.), adriamycin (20 mg/kg, i.p.) and sildenafil (20 mg/kg, p.o.) respectively. Three separate groups were pretreated with sildenafil (5, 10 and 20 mg/kg respectively) prior to adriamycin injection. Adriamycin increased activities of aspartate aminotransferase (AST), alanine aminotransferase (ALT), gamma-glutamyltransferase (GGT) and alkaline phosphatase (ALP). This was associated with degeneration and severe central venous congestion in hepatic cells and marked micronuclei formation in erythrocytes. Sildenafil (5 mg/kg) reduced AST and ALP activities by 18.7 % (p<0.001) and 14.1 % (p<0.01) respectively in the adriamycin-treated rats without any significant change in ALT and GGT activities even at 10 mg/kg. Although, sildenafil (20 mg/kg) raised GGT activity by 77.4% and 51.6% in normal and adriamycin-treated rats respectively, these effects were not significant when compared with control. Similarly, total protein and albumin did not change significantly across the various treatment groups. However, sildenafil significantly (p<0.05) increased glutathione levels at all doses and significantly reduced micronuclei formation by 65.5% and ameliorated morphological damage associated with adriamycin toxicity. Our data suggest that low doses of the phosphodiesterase-5 inhibitor, sildenafil, may protect against adriamycin-induced hepatotoxicity and genotoxicity.

Keywords

Hepatotoxicity, Genotoxicity, Adriamycin, Phosphodiesterase-5, Sildenafil.
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  • Modulation of Adriamycin-Induced Hepatotoxicity and Genotoxicity by Selective Inhibition of Phosphodiesterase-5 with Sildenafil in Wistar Rats

Abstract Views: 568  |  PDF Views: 1

Authors

Anne A. Adeyanju
Department of Biochemistry, Bowen University, Iwo, Osun State, Nigeria
Adedeji D. Ogunyemi
Department of Biochemistry, Bowen University, Iwo, Osun State, Nigeria
Oluwaseun Owolabi
Department of Biochemistry, Bowen University, Iwo, Osun State, Nigeria
Ololade Adesanya
Department of Biochemistry, Bowen University, Iwo, Osun State, Nigeria
Temilade Omideyi
Department of Biochemistry, Bowen University, Iwo, Osun State, Nigeria
Oluwasanmi O. Aina
Department of Veterinary Anatomy, University of Ibadan, Ibadan, Nigeria
Martins Ekor
Department of Pharmacology, School of Medical Sciences, University of Cape Coast, Cape Coast, Ghana

Abstract


This study investigated the effect of selective inhibition of phosphodiesterase-5 on hepatotoxicity and genotoxicity induced by adriamycin in rats. Thirty male Wistar rats (150 - 250 g) were randomly assigned into six groups of 5 rats/group. Negative, positive and sildenafil controls received physiological saline (10 ml/kg, p.o.), adriamycin (20 mg/kg, i.p.) and sildenafil (20 mg/kg, p.o.) respectively. Three separate groups were pretreated with sildenafil (5, 10 and 20 mg/kg respectively) prior to adriamycin injection. Adriamycin increased activities of aspartate aminotransferase (AST), alanine aminotransferase (ALT), gamma-glutamyltransferase (GGT) and alkaline phosphatase (ALP). This was associated with degeneration and severe central venous congestion in hepatic cells and marked micronuclei formation in erythrocytes. Sildenafil (5 mg/kg) reduced AST and ALP activities by 18.7 % (p<0.001) and 14.1 % (p<0.01) respectively in the adriamycin-treated rats without any significant change in ALT and GGT activities even at 10 mg/kg. Although, sildenafil (20 mg/kg) raised GGT activity by 77.4% and 51.6% in normal and adriamycin-treated rats respectively, these effects were not significant when compared with control. Similarly, total protein and albumin did not change significantly across the various treatment groups. However, sildenafil significantly (p<0.05) increased glutathione levels at all doses and significantly reduced micronuclei formation by 65.5% and ameliorated morphological damage associated with adriamycin toxicity. Our data suggest that low doses of the phosphodiesterase-5 inhibitor, sildenafil, may protect against adriamycin-induced hepatotoxicity and genotoxicity.

Keywords


Hepatotoxicity, Genotoxicity, Adriamycin, Phosphodiesterase-5, Sildenafil.

References





DOI: https://doi.org/10.22506/ti%2F2016%2Fv23%2Fi2%2F146694