The effects of long-term chaetomellic acid a administration on renal function and oxidative stress in a rat model of renal mass reduction

This study aimed to evaluate the effect of chronic treatment with chaetomellic acid A (CAA) on oxidative stress and renal function in amodel of renalmass reduction. Methods.MaleWistar ratswere subjected to 5/6 nephrectomy (RMR) or sham-operated (SO). One week after surgery, rats have been divided into four experimental groups: RMR: RMR rats without treatment (n = 14); RMR + CAA: RMR rats treated with CAA (n = 13); SO: SO rats without treatment (n = 13); and SO + CAA: SO rats treated with CAA (n = 13). CAA was intraperitoneally administered in a dose of 0.23 μg/Kg three times a week for six months. Results. RMR was accompanied by a significant reduction in catalase and glutathione reductase (GR) activity (p < 0.05) and a decrease in reduced glutathione (GSH)/oxidized glutathione (GSSG) ratio. CAAadministration significantly increased catalase andGR activity (p < 0.05) and increased GSH/GSSG ratio, but no significant difference between the treated and nontreated groups was found in this ratio.No significant differences were found between theRMRgroups in any of the parameters of renal function.However, CAA administration slightly improves some parameters of renal function. Conclusions. These data suggest that CAA could attenuate 5/6 RMR-induced oxidative stress.The authors would like to thank Jos´e Miguel Lopez- Novoa for valuable comments and suggestions. This work is supported by European Investment Funds by FEDER/ COMPETE/POCI, Operational Competitiveness and Internationalization Programme, under Project POCI-01-0145- FEDER-006958, and National Funds by FCT, Portuguese Foundation for Science and Technology, under Project UID/AGR/04033/2013, and by European Investment Funds by FEDER/COMPETE/POCI, Operational Competitiveness and Internationalization Programme, under Project POCI- 01-0145-FEDER-016728, and National Funds by FCT, Portuguese Foundation for Science and Technology, under Project PTDC/DTP-DES/6077/2014.info:eu-repo/semantics/publishedVersio

The Effects of Long-Term Chaetomellic Acid A Administration on Renal Function and Oxidative Stress in a Rat Model of Renal Mass Reduction

properly cited. Purpose. This study aimed to evaluate the effect of chronic treatment with chaetomellic acid A (CAA) on oxidative stress and renal function in a model of renal mass reduction. Methods. Male Wistar rats were subjected to 5/6 nephrectomy (RMR) or sham-operated (SO). One week after surgery, rats have been divided into four experimental groups: RMR: RMR rats without treatment ( = 14); RMR + CAA: RMR rats treated with CAA ( = 13); SO: SO rats without treatment ( = 13); and SO + CAA: SO rats treated with CAA ( = 13). CAA was intraperitoneally administered in a dose of 0.23 g/Kg three times a week for six months. Results. RMR was accompanied by a significant reduction in catalase and glutathione reductase (GR) activity ( &lt; 0.05) and a decrease in reduced glutathione (GSH)/oxidized glutathione (GSSG) ratio. CAA administration significantly increased catalase and GR activity ( &lt; 0.05) and increased GSH/GSSG ratio, but no significant difference between the treated and nontreated groups was found in this ratio. No significant differences were found between the RMR groups in any of the parameters of renal function. However, CAA administration slightly improves some parameters of renal function. Conclusions. These data suggest that CAA could attenuate 5/6 RMR-induced oxidative stress

Long-term treatment with chaethomellic acid A reduces glomerulosclerosis and arteriolosclerosis in a rat model of chronic kidney disease

The high prevalence of end-stage renal disease emphasizes the failure to provide therapies to effectively prevent and/or reverse renal fibrosis. Therefore, the aim of this study was to evaluate the effect of long-term treatment with chaethomellic acid A (CAA), which selectively blocks Ha-Ras farnesylation, on renal mass reduction-induced renal fibrosis. Male Wistar rats were sham-operated (SO) or subjected to 5/6 renal mass reduction (RMR). One week after surgery, rats were placed in four experimental groups: SO:SO rats without treatment (n = 13); SO + CAA: SO rats treated with CAA (n = 13); RMR:RMR rats without treatment (n = 14); and RMR + CAA:RMR rats treated with CAA (n = 13). CAA was intraperitoneally administered in a dose of 0.23 μg/kg three times a week for six months. Renal fibrosis was evaluated by two-dimensional ultrasonography and histopathological analysis. The kidneys of the RMR animals treated with CAA showed a significantly decrease in the medullary echogenicity (p < 0.05) compared with the RMR rats that received no treatment. Glomerulosclerosis and arteriolosclerosis scores were significantly lower (p < 0.001) in the RMR + CAA group when compared with the RMR group. There were no significant differences in interstitial fibrosis, interstitial inflammation and tubular dilatation scores between the RMR + CAA and RMR groups. These data suggest that CAA can be a potential future drug to attenuate the progression of chronic kidney disease.This work is supported by : European Investment Funds by FEDER/COMPETE/POCI– Operacional Competitiveness and Internacionalization Programme, under Project POCI-01-0145-FEDER-006958 and National Funds by FCT - Portuguese Foundation for Science and Technology, under the project UID/AGR/04033/2013; and by European Investment Funds by FEDER/COMPETE/POCI– Operacional Competitiveness and Internacionalization Programme, under Project POCI-01-0145-FEDER-016728 and National Funds by FCT - Portuguese Foundation for Science and Technology, under the project PTDC/DTP-DES/6077/2014.info:eu-repo/semantics/publishedVersio

New therapeutic approaches to chronic kidney disease

The main research goal in patients with chronic kidney disease (CKD) is the development of new therapeutic approaches capable of slowing down the progression to end-stage renal disease. The aim of this work was to evaluate the effects of long-term administration of chaetomellic acid A (CAA), which selectively blocks H-Ras farnesylation, on chronic kidney lesions in 5/6 nephrectomized Wistar rats, an animal model of chronic renal disease. Materials and Methods: Sixty male Wistar rats were sham-operated (SO) or submitted to 5/6 nephrectomy (RMR). One week after surgery, surviving animals were distributed into four groups: SO–SO rats receiving no treatment (n = 13); SO+CAA–SO rats receiving CAA treatment (n = 13); RMR–RMR rats receiving no treatment (n = 14); RMR+CAA–RMR rats receiving CAA treatment (n = 13). CAA was administered intraperitoneally three times a week for 6 months. Renal fibrosis was evaluated by ultrasonography and histopathological analysis. All experimental procedures followed the European (European Directive 2010/63/EU) and National (Decree-Law 113/2013) legislation on the protection of the animals used for scientific purposes. Results: The kidneys of the RMR animals treated with CAA showed a significant decrease in medullary echogenicity (P <0.05) compared with the RMR rats that received no treatment. Glomerulosclerosis and arteriolosclerosis scores were significantly lower (P <0.001) in the RMR+CAA group when compared with the RMR group. Conclusion: These data suggest that pharmacological inhibition of H-Ras proteins activation may be a future strategy in the prevention of end-stage renal disease.info:eu-repo/semantics/publishedVersio

New therapeutic approaches on chronic kidney disease

Introduction: chronic kidney disease is a serious public health problem that affects millions of patients worldwide. So, the main research goals in the CKD patients are the research of new therapeutic approaches capable of slowing down the progression to end-stage renal disease. Objective: the aim of this work, was to evaluate the effects of chronic administration of chaetomellic acid A (CAA), which selectively blocks H-Ras farnesylation, on kidney chronic lesions in 5/6 nephrectomized Wistar rats, an animal model of chronic renal disease. Material and methods: sixty male Wistar rats (Rattus norvergicus) were housed under controlled conditions. After seven weeks of acclimatization, rats (weighing 359 to 402 g) were sham-operated (SO) or submitted to 5/6 nephrectomy (RMR). One week after surgery surviving animals (n=53) were distributed into four groups: SO: SO rats receiving no treatment (n=13); SO+CAA: SO rats receiving CAA treatment (n=13); RMR: RMR rats receiving no treatment (n=14); RMR+CAA: RMR rats receiving CAA treatment (n=13). CAA was intraperitoneally administered (0.23 µg/Kg) three times a week for six months. Six months after the surgical procedure, in the left kidney of each animal was evaluated the mean cortical and medullary echogenicity by two-dimensional ultrasonography. Then, the kidneys were removed, fixed in 10% neutral-buffered formalin and processed for routine histopathological diagnosis and chronic lesions were evaluated, by Hematoxylin-Eosin, reticulin and Masson trichrome methods, for severity. All experimental procedures followed the European (European Directive 2010/63/EU) and National (Decree-Law 113/2013) legislation on the protection of the animals used for scientific purposes. Results: the kidneys of the RMR animals treated with CAA showed a significantly decrease in the medullary echogenicity (p<0.05) compared with the RMR rats that received no treatment. Glomerulosclerosis and arteriolosclerosis scores were significantly lower (p<0.001) in the RMR+CAA group when compared with the RMR group. There were no significant differences in interstitial fibrosis, interstitial inflammation and tubular dilatation scores between the RMR+CAA and RMR groups.Conclusion: this data suggests that pharmacological inhibition of H-Ras proteins activation may be a future strategy in the prevention of end-stage renal disease.This work is financed by national funds through FCT - Fundação para a Ciência e Tecnologia, I.P., under the project UID/Multi/04016/2016. Furthermore we would like to thank the Instituto Politécnico de Viseu, CI&DETS for their support and FCT, FCOMP-01-0124-FEDER-009525; IPV, CI&DETS, FCT and QREN/FEDER (Ovislab ICT-2013-05-004-5314 ID-64757). This work is supported by European Investment Funds by FEDER/COMPETE/POCI– Operacional Competitiveness and Internacionalization Programme, under Project POCI-01-0145-FEDER-006958 and National Funds by FCT - Portuguese Foundation for Science and Technology, under the project UID/AGR/04033/2013. Furthermore we would like to thank to UTAD and CITABS for their support.info:eu-repo/semantics/publishedVersio