Protective role of polyphenols in cyclosporine A-induced nephrotoxicity during rat pregnancy.
The aim of this study was to evaluate the adverse effects of cyclosporine A (CsA) toward renal morphogenesis and to test the renoprotective natural antioxidants such as provinol (PV). Pregnant rats were divided into four groups. Group I was injected SC with olive oil. Group II was treated with oral administration of PV and was used as control. Group III animals were injected SC daily with CsA, and group IV animals were injected daily with CsA and PV for 21 days of pregnancy. Five pups per litter were killed and the kidneys removed and treated by morphological and immunohistochemical (IHC) methods. IHC analysis considered two proteins responsible for nephrotoxicity in adult rats: inducible nitric oxide (iNOS) and matrix metalloproteinase-2 (MMP2). Pregnancy outcomes among CsA-treated rats demonstrated a reduced number of pups. Pups that were exposed antenatally to CsA presented several pathologic findings in all immature parenchyma and an increase in iNOS and MMP2 expression. These side effects were not observed in kidney of litters born from CsA + PV-treated mothers. Our study indicates that CsA induces morphological alterations in renal parenchyma of neonates and that PV plays a protective role against these side effects.
Rezzani
Rita
R
Department of Biomedical Sciences and Biotechnology, Division of Human Anatomy, University of Brescia, 25123, Brescia, Italy. rezzani@med.unibs.it
Rodella
Luigi Fabrizio
LF
Tengattini
Sandra
S
Bonomini
Francesca
F
Pechánová
Olga
O
Kojsová
Stanislava
S
Andriantsitohaina
Ramaroson
R
Bianchi
Rossella
R
D000818:Animals; D000831:Animals, Newborn; D000975:Antioxidants / Q000627:therapeutic use*; D001835:Body Weight / Q000187:drug effects; D016572:Cyclosporine / Q000009:adverse effects*; D005260:Female; D005419:Flavonoids / Q000627:therapeutic use*; D007166:Immunosuppressive Agents / Q000009:adverse effects*; D007668:Kidney / Q000187:drug effects* / Q000196:embryology / Q000473:pathology; D007674:Kidney Diseases / Q000139:chemically induced / Q000151:congenital / Q000517:prevention & control*; D007678:Kidney Glomerulus / Q000187:drug effects / Q000196:embryology / Q000473:pathology; D008098:Litter Size / Q000187:drug effects; D008297:Male; D008431:Maternal-Fetal Exchange; D020778:Matrix Metalloproteinase 2 / Q000096:biosynthesis; D009024:Morphogenesis / Q000187:drug effects; D052247:Nitric Oxide Synthase Type II / Q000096:biosynthesis; D010636:Phenols / Q000627:therapeutic use*; D059808:Polyphenols; D011247:Pregnancy; D051381:Rats; D017208:Rats, Wistar
D000975:Antioxidants; D005419:Flavonoids; D007166:Immunosuppressive Agents; D010636:Phenols; D059808:Polyphenols; D016572:Cyclosporine; D052247:Nitric Oxide Synthase Type II; D020778:Matrix Metalloproteinase 2