The restoration of kidney mitochondria function by inhibition of angiotensin-II production in rats with acute adriamycin-induced nephrotoxicity

Abstract

Adriamycin (ADR) is commonly used for many solid tumor treatments. Its clinical utility is, however, largely limited by the adverse reactions, are known to be nephrotoxic. The mechanism by which it induces kidney damage is still not completely understood, but its nephrotoxicity might relate to increase reactive oxidant status (ROS), mitochondrial dysfunction. Until now, neurohormonal activation of it is unclear. ADR might activate the renin angiotensin system. Angiotensin-II also induced ROS and mitochondrial dysfunction. The aim of this study was to investigate whether angiotensin-II production inhibition has the protective effect on attenuation of mitochondrial function in rats with acute ADR-nephrotoxicity or not. Rats were divided into five groups as a control, ADR, co-treated ADR with captopril (CAP), co-treated ADR with Aliskren, co-treated ADR with both CAP and Aliskren groups. Creatinine kinase (CK) levels were measured at the end of treatment period. The kidneys were homogenized and biochemical measurements were made in mitochondria, cytosol. Mitochondria membrane potential (MMP) and ATP levels were determined. ADR increased CK levels and oxidative stress in mitochondria too (p50.05). ADR significantly decreased MMP and ATP level in kidney mitochondria (p50.05). Co-administration with ADR and Aliskren and CAP improved the dissipation of MMP (p50.05). The decrease in ATP level was restored by treatment with inhibitors of ACE and renin. We concluded that inhibitors of angiotensin-II are effective against acute ADR induced nephrotoxicity via the restoration of MMP and ATP production and prevention of mitochondrial damage in vivo. KeywordsAdriamycin-induced nephrotoxicity, Aliskren, captopril, mitochondrial ATP, mitochondrial membrane potential, oxidative stress index History

Inhibition of Angiotensin-II Production Increases Susceptibility to Acute Ischemia/Reperfusion Arrhythmia

“…Myocardial mitochondria were separated as described before [7,9]. The mitochondria and cytosol were kept at −80°C until use for measurement of oxidative stress index.…”

Counteraction of Apoptotic and Inflammatory Effects of Adriamycin in the Liver Cell Culture by Clinopitolite

“…One of the anthracycline antibiotics is adriamycin (ADR). Although it has a great therapeutic effect on tumor tissues, it also has, unfortunately, some undesirable effects which cause cytotoxic effect on non-cancerous tissues including the heart [1], kidney [2], liver [3], testis [4], or brain [5]. Growing evidence has been reported on ADR's hepatotoxicity in literature.…”

Recovery of adriamycin induced mitochondrial dysfunction in liver by selenium

“…The measurement of mitochondrial functions and mitochondria derived oxidative stress were performed in the mitochondria and cytosol parts from liver tissues as described before Taskin and Dursun 2012;Taskin et al 2014). Liver tissue homogenization was firstly performed in icecold buffer.…”

“…Among the various chemotherapeutic drugs, adriamycin (ADR) is widely used an anthracycline drug due to its therapeutic efficacy on a wide spectrum of solid and childhood cancers (Ingawale et al 2014;Manjanatha et al 2014;Qian et al 2011;Raskovic et al 2011). However, this anti-cancer drug also produces significant toxic side effect by damaging heart (Raskovic et al 2011), liver (Wang et al 2014), and kidney (Taskin and Dursun 2012;Taskin et al 2014). The possibilities of how to minimize the effect of ADR induced toxicities on noncancerous tissues like liver, heart, kidney has, therefore, become quite an important research goal (Alshabanah et al 2010;Hanusova et al 2013;Qian et al 2011;Raskovic et al 2011).…”

“…ADR tends to diffuse from cytosol to mitochondria and accumulates there. Mitochondria are an organel responsible for many cellular process, e.g., producing ATP depented its membrane potential Taskin and Dursun 2012;Taskin et al 2014). Reactive oxygen species are physiologically produced during the oxidative phosphorylation process in the mitochondria, so mitochondria also contain some antioxidant enzymes, including CAT, SOD etc to detoxify them.…”