Experimental evaluation of furosemide and/or tadalafil in conventional
and nanoparticle forms in prevention of chronic renal failure induced in
rats.
Abstract
Introduction: Chronic renal failure (CRF) is a progressive loss of renal
function that lead to reduced sodium filtration and inappropriate
suppression of tubular reabsorption that ultimately leads to volume
expansion. To improve treatment outcomes, the aim of this study was to
evaluate the possible renoprotective effect of tadalafil and furosemide,
individually and in combination, in both conventional and nanoforms in
adenine-induced CRF rat-model. Methods: Addition of 0.75% adenine to
the diet of rats for 4 weeks gained general acceptance as a model to
study kidney damage as this intervention mimicked most of the structural
and functional changes seen in human chronic kidney disease Urine
analysis, histopathological changes and immunohistochemical expression
of caspase-3 and interleukin-1β (IL-1β) in renal tissues were performed.
Results: Our results showed that the combination of tadalafil and
furosemide using conventional and nanoparticle formulations revealed a
beneficial therapeutic effect in the treatment of CRF. This was
demonstrated by improvement of urinary, serum and renal tissue markers
as indicative of organ damage. This was also reflected on the reduction
of tubular expression of KIM-1 and NGAL. Immunohistochemical studies
showed that significant increase in the number of apoptotic tubular
cells indicated by increased expression of caspase-3 in CRF. These
deteriorated renal cellular changes were improved by the treatment of
rats with the investigated drugs. Results from ELISA showed that IL-1β
was reduced by such treatment in kidney tissue. Conclusion: Tadalafil
and furosemide improved the biochemical, histopathological and
immunohistochemistry changes in adenine-induced CRF which strongly
support the renopreventive effects of investigated drugs in particular
the nanoparticle forms.