Renal Toxicity of Lisinopril and Rosuvastatin, Alone and in Combination, in Wistar Rats

Dodiya, Hardik; Jain, Mukul; Goswami, Sumanta

doi:10.1177/1091581811415293

Cited by 12 publications

(12 citation statements)

References 9 publications

(17 reference statements)

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“…Although data on the potential renal toxicity of high-potency statins are controversial (Tiwari 2006; Golomb and Evans 2008; Dodiya et al 2011), two meta-analyses showed that statin therapy is safe and effective in preventing mortality and major cardiovascular events in patients with non-dialysis-dependent chronic kidney disease (CKD) (Upadhyay et al 2012, 2013; Palmer et al 2012). However, these studies provide very limited evidence to support the use of statins in patients on dialysis, and statin therapy was not found to be effective in reducing the risk of kidney failure or decline in kidney function (Upadhyay 2013).…”

Section: Discussionmentioning

confidence: 99%

Dietary supplementation with essential amino acids boosts the beneficial effects of rosuvastatin on mouse kidney

et al. 2014

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The effects of high-potency statins on renal function are controversial. To address the impact of statins on renal morpho-functional aspects, normotensive young mice were treated with rosuvastatin (Rvs). Moreover, because statins may impair mitochondrial function, mice received either dietary supplementation with an amino acid mixture enriched in essential amino acids (EAAm), which we previously demonstrated to increase mitochondrial biogenesis in muscle or an unsupplemented control diet for 1 month. Mitochondrial biogenesis and function, apoptosis, and insulin signaling pathway events were studied, primarily in cortical proximal tubules. By electron microscopy analysis, mitochondria were more abundant and more heterogeneous in size, with dense granules in the inner matrix, in Rvs- and Rvs plus EAAm-treated animals. Rvs administration increased protein kinase B and endothelial nitric oxide synthase phosphorylation, but the mammalian target of rapamycin signaling pathway was not affected. Rvs increased the expression of sirtuin 1, peroxisome proliferator-activated receptor γ coactivator-1α, cytochrome oxidase type IV, cytochrome c, and mitochondrial biogenesis markers. Levels of glucose-regulated protein 75 (Grp75), B-cell lymphoma 2, and cyclin-dependent kinase inhibitor 1 were increased in cortical proximal tubules, and expression of the endoplasmic reticulum–mitochondrial chaperone Grp78 was decreased. EAAm supplementation maintained or enhanced these changes. Rvs promotes mitochondrial biogenesis, with a probable anti-apoptotic effect. EAAm boosts these processes and may contribute to the efficient control of cellular energetics and survival in the mouse kidney. This suggests that appropriate nutritional interventions may enhance the beneficial actions of Rvs, and could potentially prevent chronic renal side effects.

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Section: Discussionmentioning

confidence: 99%

Dietary supplementation with essential amino acids boosts the beneficial effects of rosuvastatin on mouse kidney

et al. 2014

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“…Such was the case for immunosuppression following cyclosporin A treatment, antiproliferative effects and bone marrow suppression following doxorubicin treatment, and the kidney toxicity following captopril or lisinopril treatment [65]. On the other hand, where a mechanistic pattern had not been developed for cardiotoxicity, no prediction of this effect could be possible even for a treatment such as doxorubin, where cardiomyopathy is the major adverse effect in both rats and humans [27, 66], albeit analysis of significantly changed individual metabolites has the potential to suggest such toxicity (data not shown).…”

Section: Discussionmentioning

confidence: 99%

Prediction of Clinically Relevant Safety Signals of Nephrotoxicity through Plasma Metabolite Profiling

Mattes¹,

Kamp

Fabian

et al. 2013

BioMed Research International

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Addressing safety concerns such as drug-induced kidney injury (DIKI) early in the drug pharmaceutical development process ensures both patient safety and efficient clinical development. We describe a unique adjunct to standard safety assessment wherein the metabolite profile of treated animals is compared with the MetaMap Tox metabolomics database in order to predict the potential for a wide variety of adverse events, including DIKI. To examine this approach, a study of five compounds (phenytoin, cyclosporin A, doxorubicin, captopril, and lisinopril) was initiated by the Technology Evaluation Consortium under the auspices of the Drug Safety Executive Council (DSEC). The metabolite profiles for rats treated with these compounds matched established reference patterns in the MetaMap Tox metabolomics database indicative of each compound's well-described clinical toxicities. For example, the DIKI associated with cyclosporine A and doxorubicin was correctly predicted by metabolite profiling, while no evidence for DIKI was found for phenytoin, consistent with its clinical picture. In some cases the clinical toxicity (hepatotoxicity), not generally seen in animal studies, was detected with MetaMap Tox. Thus metabolite profiling coupled with the MetaMap Tox metabolomics database offers a unique and powerful approach for augmenting safety assessment and avoiding clinical adverse events such as DIKI.

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“…Despite its wide scale use, cases of clinically apparent acute liver injury and deaths attributed to lisinopril complications have been 1 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 published [15,16] . Strikingly, lisinopril have been associated with instances of acute liver injury after 1-4 years of therapy, a distinctly unusual pattern of drug induced liver injury [17][18][19] .…”

Section: Introductionmentioning

confidence: 99%

Research on garlic capsule and selenium-vitamin A, vitamin B, vitamin C applied in therapy of acute hepatocellular damage in a rat model

Akintunde

Bolarin

2015

Journal of Acute Disease

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A B S T R A C TObjectives: To evaluate the toxicity of lisinopril in liver of male rats and its reversal effect of garlic capsule (GAR) and selenium-vitamin A, vitamin B, vitamin C (SACE). Methods: Thirty five adult male wistar rats were randomly assigned into 5 groups of 7 animals per group. Group I serves as the control, animals in Groups II, III, IV and V received 28 mg/kg body weight of lisinopril via oral route. Group III was co-treated with GAR at therapeutic dose of 250 mg/kg body weight per day. Group IV was co-treated with SACE at dose of 500 mg/kg body weight. Lastly, group V was co-treated with GAR and SACE at doses of 250 and 500 mg/kg body weight respectively, and the experiment last for 8 days.Results: Administration of lisinopril caused systemic toxicity in liver as well as adverse histopathologic changes in the tested tissue. While GAR and SACE significantly (P < 0.05) reversed the toxic effects induced by lisinopril. Conclusions: Collectively, the results suggest that therapeutic dose of lisinopril elicits toxicity in male rats through induction of oxidative damage and depletion of cellular adenosine triphosphate. The reversal effects of GAR and SACE during lisinopril treatment suggest that these antioxidants may find clinical application in cellular damage involving ROS and adenosine triphosphate.

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Renal Toxicity of Lisinopril and Rosuvastatin, Alone and in Combination, in Wistar Rats

Cited by 12 publications

References 9 publications

Dietary supplementation with essential amino acids boosts the beneficial effects of rosuvastatin on mouse kidney

Dietary supplementation with essential amino acids boosts the beneficial effects of rosuvastatin on mouse kidney

Prediction of Clinically Relevant Safety Signals of Nephrotoxicity through Plasma Metabolite Profiling

Research on garlic capsule and selenium-vitamin A, vitamin B, vitamin C applied in therapy of acute hepatocellular damage in a rat model

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