Renal ischemia and reperfusion injury: influence of chorpromazine on renal function and lipid peroxidation

Abstract

Purpose: To evaluate the influence of chlorpromazine (CPZ) on renal function and lipid peroxidation in a rat model of kidney ischemia/reperfusion injury. Methods: Forty eight Wistar rats underwent a laparotomy for hilar clamping of left kidney with a bulldog clamp for 60 minutes followed by organ reperfusion and contralateral nephrectomy. Of these, 26 received 3mg/kg of CPZ intravenously 15 minutes before renal ischemia (G-E) while the remaining 22 were used as ischemic control group (G-C). Eleven rats of G-E and 8 of G-C were followed for blood urea nitrogen and creatinine determinations before renal ischemia and at 1 st , 4 th and 7 th postoperative days. Samplings of left renal tissue were obtained at 5 minutes (5 rats from each group) and 24 hours (9 G-C and 10 of G-E) of reperfusion for malondialdehy (MDA) content determination. Controls of renal MDA content were determined in kidneys harvested from 6 additional normal rats. Results: Acute renal failure occurred in all animals but levels of BUN and creatinine were significantly lower in G-E (p<0.001). MDA content rose strikingly at 5 minutes of reperfusion in both groups (p>0.05) and returned near to normal levels 24 hours later. Conclusion: CPZ conferred partial protection of renal function to kidneys submitted to ischemia/reperfusion injury that seems to be not dependent on inhibition of lipid peroxidation. Key words:Renal Ischemia/Reperfusion. Lipid Peroxidation. Malondialdehyde. Chlorpromazine. Free Radicals. RESUMOObjetivo: avaliar a influência da clorpromazina (CPZ) na função renal e na peroxidação lipídica num modelo de lesão de isquemia/reperfusão renal em ratos. Métodos: 48 ratos Wistar foram submetidos à laparotomia para clampamento da artéria renal esquerda durante 60 minutos, seguido da reperfusão e nefrectomia contralateral. Destes animais, 26 receberam 3 mg/ kg de CPZ intravenosa 15 minutos antes da isquemia renal (G-E), sendo os 22 animais restantes utilizados como grupo controle isquêmico (G-C). Em 11 ratos do G-E e 8 do G-C foi feita a dosagem de uréia e creatinina sérica antes da isquemia renal e no 1º, 4º e 7º dia pós-operatório. Amostras de tecido do rim esquerdo foram obtidas aos 5 minutos (5 ratos de cada grupo) e 24 horas após reperfusão (9 G-C e 10 G-E) para dosagem de malondialdeído (MDA). Valores controle para níveis de MDA foram obtidos em rins retirados de 6 ratos normais. Resultados: insuficiência renal aguda ocorreu em todos os animais mas os níveis séricos de uréia e creatinina foram significativamente menores no G-E (p<0,001). Os níveis de MDA apresentaram elevação acentuada na avaliação aos 5 minutos de reperfusão em ambos os grupos (p<0,05), retornando a valores próximos aos normais na avaliação com 24 horas. Conclusão: a CPZ conferiu proteção parcial da função renal aos rins submetidos à lesão de isquemia e reperfusão, aparentemente independente da inibição da peroxidação lipídica.

The Effect of Gender on Brain Tissue Changes Induced by Renal Ischemia-Reperfusion Injury in Adult Rats

“…In a study of the effect of chlorpromazine on IRI after 60 minutes of ischemia and reperfusion after 5 minutes and 24 hours, Tucci Junior et al showed that MDA levels increased significantly within 5 minutes but returned to its normal level within 24 hours. They attributed their finding to the fact that lipid peroxidation process plays a role in renal injury at the anoxic and pre-reperfusion stages, and MDA level increases and then decreases at the beginning of the reperfusion stage (16). In the present study, the serum nitrite level increased in female rats, which may be due to the effect of female sex hormones on increased NOS expression (17).…”

The influence of renal ischemia-reperfusion injury on remote organs

“…[ 32 33 ] It is thought that increasing of MDA concentration occurs in initial times of renal reperfusion, but it returns to near-normal levels 24 h later. [ 34 ] It is known that sex difference in kidney levels of MDA may be related to antioxidant properties of the female sex hormones, estrogen, that can reduce free radicals. [ 35 ] Hence, increased activity of superoxide dismutase or other antioxidant enzymes leads to a reduction in the MDA level.…”

Influence of chlorpromazine on renal histology of rats submitted to ischemia and reperfusion injury

“…From 2001 onwards, new publications, produced in Brazil, have emerged and they show the beneficial usage of chlorpromazine in renal ischemia episodes induced towards renal transplant 13,15,16,18 . The last publication about chlorpromazine was published in 2010 18 , and for this reason new studies are necessary to confirm the benefits of this drug in renal ischemia; it's a cheap and easy-to-use drug.…”

“…There have also been studies towards lipid peroxidation (malondialdehyde count) 16 ; however, such study has alternatively focused on a number of histological items caused by ischemia related to renal architecture and chlorpromazine protective action.…”