Low-dose carvedilol protects against acute septic renal injury in rats during the early and late phases.
Recent findings from septic acute renal injury studies have implicated the mitochondrion as an important factor in kidney injury, and that increased sympathetic nerve activity may contribute to the induction of organ failure. This study investigated the impact of a nondepressor dose of carvedilol, which is a beta-adrenoreceptor antagonist with antioxidant activity, on septic renal injury induced in rats with cecal ligation and puncture (CLP). Three groups of rats were studied. The first group was the sham-operated control. The other 2 groups of rats underwent CLP, and were administered either the vehicle or carvedilol (2.0 mg/kg body mass, by intraperitoneal (i.p.) injection, daily for 2 days as well as 30 min prior to CLP). Kidney function, inflammatory parameters, mitochondrial function, and renal perfusion pressure (RPP) were investigated at 6 and 18 h after CLP. Carvedilol did not significantly induce hypotension, and it significantly improved RPP and renal dysfunction induced with CLP, together with significant reductions in serum levels of interleukin 6 and tumor necrosis factor-alpha. Septic kidney injury mediated increased levels of malondialdehyde and protein carbonyls. Carvedilol also attenuated the decrease in kidney mitochondrial glutathione and nicotinamide adenine dinucleotide phosphate dehydrogenase. Further, intracellular renal edema and inflammation induced with CLP were reduced with carvedilol. These findings suggest renoprotective effects of carvedilol in sepsis.
Department of Pharmacology, Faculty of Medicine, Ain Shams University, Ramsis Street, Abbassia, Cairo, Egypt.
Hala Salah
HS
Abdel Kawy
D058186:Acute Kidney Injury / Q000097:blood / Q000188:drug therapy* / Q000378:metabolism; D000818:Animals; D002227:Carbazoles / Q000008:administration & dosage*; D000077261:Carvedilol; D004195:Disease Models, Animal; D005978:Glutathione / Q000378:metabolism; D007249:Inflammation / Q000097:blood / Q000188:drug therapy; D015850:Interleukin-6 / Q000097:blood; D007668:Kidney / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D009252:NADPH Dehydrogenase / Q000378:metabolism; D011412:Propanolamines / Q000008:administration & dosage*; D020011:Protective Agents / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D018805:Sepsis / Q000097:blood / Q000188:drug therapy* / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000097:blood
D002227:Carbazoles; D015850:Interleukin-6; D011412:Propanolamines; D020011:Protective Agents; D014409:Tumor Necrosis Factor-alpha; D000077261:Carvedilol; D008315:Malondialdehyde; D009252:NADPH Dehydrogenase; D005978:Glutathione
antagoniste des récepteurs bêta adrénergiques; beta-adrenoreceptor antagonist; cecal ligation and puncture; fonction mitochondriale; ligature et perforation du cæcum; mitochondrial function; pression de perfusion rénale; renal perfusion pressure