Angiotensin II-induced hypertension increases the mutant frequency in rat kidney

Hartmann, Christina; Schulz, Ina; Epe, Bernd; Schupp, Nicole

doi:10.1007/s00204-019-02477-8

Cited by 6 publications

(7 citation statements)

References 51 publications

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“…While we were not able to find a significant increase in oxidative stress measured directly on kidney tissue neither with a redox-sensitive dye nor with an antibody against the oxidative base modification 8-oxodG or in urine in contrast to our previous studies with aldosterone- or angiotensin II-induced hypertension [ 20 , 28 , 29 ], we did find significantly increased excretion of the lipid peroxidation marker 15-isoprostane F 2t . The only tendential increases of the markers could be due to the high interindividual variation found in the mice used in this pilot study.…”

Section: Discussioncontrasting

confidence: 99%

Aldosterone Induces DNA Damage and Activation of Nrf2 Mainly in Tubuli of Mouse Kidneys

Balhorn

Hartmann

Schupp

2020

IJMS

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Hypertensive patients have an increased risk of developing chronic kidney disease (CKD). Many of these patients have increased levels of the blood pressure regulating mineralocorticoid aldosterone. As a protection against aldosterone-induced damage, kidney cells can upregulate key regulators of the antioxidant defense, such as nuclear factor-erythroid-2-related factor 2 (Nrf2). In the present study aldosterone-induced kidney damage and Nrf2 activation in kidney cells of mice treated with three different concentrations of aldosterone for 4 weeks was localized. Increased albumin and neutrophil gelatinase-associated lipocalin (NGAL) in urine revealed an impaired kidney function of the aldosterone-infused mice. Localization of aldosterone-induced oxidative damage (in the form of DNA lesions) in specific kidney cells showed an increase in proximal tubuli and to an even greater extend in distal tubuli. Phosphorylated Nrf2 was increased in distal tubule cells after aldosterone-infusion. Nrf2 activation in proximal tubuli or in glomeruli after aldosterone-treatment could not be observed. Nrf2 target genes and proteins analyzed, paradoxically, showed a downregulation in the whole kidney. Aldosterone-treated mice exhibited an increased kidney injury and DNA damage in distal and proximal tubuli. Nrf2 seemed only to be specifically activated in distal tubule cells, where we also detected the highest amount of oxidative damage.

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Section: Discussioncontrasting

confidence: 99%

Aldosterone Induces DNA Damage and Activation of Nrf2 Mainly in Tubuli of Mouse Kidneys

Balhorn

Hartmann

Schupp

2020

IJMS

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“…Ang II is the main factor responsible for the pro-oxidative state that leads to accumulation of mutations in different organs affected by hypertension such as kidneys. For this reason, hypertensive patients with over-activated RAAS and high concentrations of Ang II would have an increased risk of developing renal cancer, in accordance with the results revealed by different epidemiological studies [ 124 ].…”

Section: Interrelation Among Oxidative Stress Raas and Sars-cov-supporting

confidence: 84%

Implications of Oxidative Stress and Potential Role of Mitochondrial Dysfunction in COVID-19: Therapeutic Effects of Vitamin D

et al. 2020

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Due to its high degree of contagiousness and like almost no other virus, SARS-CoV-2 has put the health of the world population on alert. COVID-19 can provoke an acute inflammatory process and uncontrolled oxidative stress, which predisposes one to respiratory syndrome, and in the worst case, death. Recent evidence suggests the mechanistic role of mitochondria and vitamin D in the development of COVID-19. Indeed, mitochondrial dynamics contribute to the maintenance of cellular homeostasis, and its uncoupling involves pathological situations. SARS-CoV-2 infection is associated with altered mitochondrial dynamics with consequent oxidative stress, pro-inflammatory state, cytokine production, and cell death. Furthermore, vitamin D deficiency seems to be associated with increased COVID-19 risk. In contrast, vitamin D can normalize mitochondrial dynamics, which would improve oxidative stress, pro-inflammatory state, and cytokine production. Furthermore, vitamin D reduces renin–angiotensin–aldosterone system activation and, consequently, decreases ROS generation and improves the prognosis of SARS-CoV-2 infection. Thus, the purpose of this review is to deepen the knowledge about the role of mitochondria and vitamin D directly involved in the regulation of oxidative stress and the inflammatory state in SARS-CoV-2 infection. As future prospects, evidence suggests enhancing the vitamin D levels of the world population, especially of those individuals with additional risk factors that predispose to the lethal consequences of SARS-CoV-2 infection.

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“…Though most of these induced renal cell carcinoma models could seem today somewhat outdated, they have remained very valuable tools to investigate the renal oncogenic potential of various molecules until now. In a study published in 2019 by Hartmann and al., for example, the renal oncogenic effects of angiotensin II were investigated in Big Blue rats [79]. In a study published by Borghoff et al in 2017, the development of kidney tumors following exposure of rats to ethyl tertiary-butyl ether and tertiary-butyl alcohol was studied as well [80].…”

Section: Animal Models Of Kidney Carcinomas Induced By Other Factorsmentioning

confidence: 99%

“…In the study by Hartmann and al. published in 2019, it was shown, for example, that exposure to angiotensin II lead to GC → T:A transversions in the transgenic lacI genes of Big Blue rats [79], but in most of the aforementioned models induced by carcinogens especially, the pathophysiology underlying renal carcinogenesis would need to be studied more in depth to allow us to better understand, and maybe prevent, renal cancer development.…”

Section: Animal Models Of Kidney Carcinomas Induced By Other Factorsmentioning

confidence: 99%

Heading Towards a Possible Rebirth of the Induced Renal Cell Carcinoma Models?

Mazzola¹,

Ribatti

2020

Cancers

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Introduction: Animal models are interesting tools to improve our knowledge of the pathophysiological processes underlying kidney cancer development. Recent advances have been made in the understanding of the genetic founding events underlying clear cell renal carcinoma. The aim of this paper was to review and discuss the characteristics of all the induced animal models of renal carcinogenesis that have been described in the scientific literature to date and to see if and how they could regain some use in the light of the latest discoveries. Methods: The authors reviewed all the papers available in PubMed regarding induced animal models of renal carcinogenesis. From this perspective, the keywords “induced”, “animal model”, and “renal cancer” were used in PubMed’s search engine. Another search was done using the keywords “induced”, “animal model”, and “kidney cancer”. PRISMA recommendations were used to develop the literature review. Results: Seventy-eight studies were included in this review. Results were presented depending on the mechanisms used to induce carcinogenesis in each model: induction by carcinogens, hormones, viral induction, or induction by other agents. Discussion focused on the possibility to rethink these different induced animal models and use them to answer new research questions. Conclusion: Many induced animal models have been developed in the past to study renal cancer. While these models seemed unable to yield new knowledge, the latest advances in the understanding of the genetics behind renal carcinogenesis could well bring the models back to the forefront.

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Angiotensin II-induced hypertension increases the mutant frequency in rat kidney

Cited by 6 publications

References 51 publications

Aldosterone Induces DNA Damage and Activation of Nrf2 Mainly in Tubuli of Mouse Kidneys

Aldosterone Induces DNA Damage and Activation of Nrf2 Mainly in Tubuli of Mouse Kidneys

Implications of Oxidative Stress and Potential Role of Mitochondrial Dysfunction in COVID-19: Therapeutic Effects of Vitamin D

Heading Towards a Possible Rebirth of the Induced Renal Cell Carcinoma Models?

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