3 research outputs found
In vivo effect of the natural antioxidant hydroxytyrosol on cyclosporine nephrotoxicity in rats
Background. Cyclosporine A (CsA) is the first-line immunosuppressant
used in transplant patients and in autoimmune
diseases. Nephrotoxicity is the major limitation
of CsA use. Although the mechanisms of nephrotoxicity
have not been completely defined, some evidence suggests
that reactive oxygen species (ROS) play a causal role. The
present study was designed to investigate in vivo effects of
hydroxytyrosol (DOPET), a natural olive oil antioxidant,
on oxidative stress, renal histology and haemodynamic alterations
induced in rats by CsA treatment.
Methods. Adult Sprague–Dawley ratswere treated i.p. with
CsA (15 mg/kg) alone or in combination with DOPET (20
mg/kg) for 3 weeks. At the end of the treatment, superoxide
concentration within the cells of the abdominal aorta
and renal artery was quantified from the oxidation of dihydroethidium
(DHE) using fluorescence microscopic imaging
analysis. In kidney tissues, lipid peroxidation was measured
by thiobarbituric acid-reacting substances (TBARS)
assay, glutathione level was assessed enzymatically and
the expression of haem oxygenase-1 (HO-1) gene was
evaluated by semiquantitative RT-PCR. Renal morphology
was studied by classical histological techniques, while the
glomerular filtration rate (GFR) was estimated by inulin
clearance. Systemic blood pressure was monitored by the
tail method and through the catheterization of the carotid
artery.
Results. CsA administration increased superoxide concentration
both in the aorta and in the renal artery, while
DOPET completely prevented this effect. Higher levels
of TBARS, a significant decrease in GSH and an upregulation
of HO-1 mRNA were observed in the kidneys of
CsA-treated rats. DOPET treatment reversed quantitatively
these effects. However, CsA-dependent changes in renal
Correspondence and offprint requests to: Giovambattista Capasso, Chair
of Nephrology, Second University of Napoli, Padiglione 17 Policlinico
Nuovo, Via Pansini 5, 80131 Napoli, Italy. Tel: +39-081-5666652; Fax:
+39-081-5666652; E-mail: [email protected]
histology were only partially reversed by DOPET. Finally,
CsA induced a severe reduction in GFR and a significant
increase in both systolic and diastolic blood pressure; the
DOPET treatment had no significant effect on these haemodynamic
alterations.
Conclusion. The reported data indicate that effective
DOPET protection from CsA-induced oxidative stress is
associated with a mild effect on histological damages and
does not affect the altered glomerular function and the hypertension,
thus indicating that kidney injury by CsA is
only in part dependent on oxidative stress.Background. Cyclosporine A (CsA) is the first-line immunosuppressant used in transplant patients and in auto- immune diseases. Nephrotoxicity is the major limitation of CsA use. Although the mechanisms of nephrotoxicity have not been completely defined, some evidence suggests that reactive oxygen species (ROS) play a causal role. The present study was designed to investigate in vivo effects of hydroxytyrosol (DOPET), a natural olive oil antioxidant, on oxidative stress, renal histology and haemodynamic alterations induced in rats by CsA treatment. Methods. Adult Sprague-Dawley rats were treated i.p. with CsA (15 mg/kg) alone or in combination with DOPET (20 mg/kg) for 3 weeks. At the end of the treatment, superoxide concentration within the cells of the abdominal aorta and renal artery was quantified from the oxidation of dihydroethidium (DHE) using fluorescence microscopic imaging analysis. In kidney tissues, lipid peroxidation was measured by thiobarbituric acid-reacting substances (TBARS) assay, glutathione level was assessed enzymatically and the expression of haem oxygenase-1 (HO-1) gene was evaluated by semiquantitative RT-PCR. Renal morphology was studied by classical histological techniques, while the glomerular filtration rate (GFR) was estimated by inulin clearance. Systemic blood pressure was monitored by the tail method and through the catheterization of the carotid artery. Results. CsA administration increased superoxide concentration both in the aorta and in the renal artery, while DOPET completely prevented this effect. Higher levels of TBARS, a significant decrease in GSH and an upregulation of HO-1 mRNA were observed in the kidneys of CsA-treated rats. DOPET treatment reversed quantitatively these effects. However, CsA-dependent changes in renal histology were only partially reversed by DOPET. Finally, CsA induced a severe reduction in GFR and a significant increase in both systolic and diastolic blood pressure; the DOPET treatment had no significant effect on these haemodynamic alterations. Conclusion. The reported data indicate that effective DOPET protection from CsA-induced oxidative stress is associated with a mild effect on histological damages and does not affect the altered glomerular function and the hypertension, thus indicating that kidney injury by CsA is only in part dependent on oxidative stress. © The Author [2007]. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved