Mitochondria-targeted peptides prevent on contrast-induced acute kidney injury in the rats with hypercholesterolemia

Abstract

Objective: The objective of this study is to evaluate the effect and mechanism of mitochondriatargeted peptides (MTP131 and SPI20) on contrast-induced acute kidney injury (CI-AKI) in rats with hypercholesterolemia. Method: Forty SD rats were randomly divided into normal diet group (NN, n ¼ 8) and high cholesterol supplemented dietary group (HN, n ¼ 32). At the end of 8 weeks, the group HN was divided into four subgroups. All Rats were given injection of either diatrizoate (10 mL/kg) or equal volume of normal saline, the rats pretreated with MTP131 or SPI20 were given injection with MTP131 or SPI 20 (3 mg/kg) by peritoneal cavity for 3 times. Blood, urine and renal tissue samples were prepared to determine biochemical parameters. The renal pathological changes were evaluated by hematoxylin and eosin staining and scored semiquantitatively, The protein expression of renal NOX4 was also measured by Western blotting. Results: In diatrizoate-injected rats, Serum creatinine (Scr), fractional excretion of sodium (FeNa%), fractional excretion of potassium (FeK%), pathological scores, renal malondialdehyde (MDA) content, the NADPH oxidase activity and the expression of NOX4 in kidney tissue were significantly increased (p50.01). In the groups pretreated with MTP131 or SPI20, the levels of Scr, FeNa%, FeK%, MDA content and NADPH oxidase activity in renal tissue decreased (p50.01), the levels of renal super oxygen dehydrogenises and ATPase activity increased (p50.01). The renal injuries induced by contrast media (CM) were alleviated. Conclusion: MTP131 and SPI20 might protect acute kidney injury induced by CM in rats with hypercholesterolemia.

Serendipity and the Discovery of Novel Compounds That Restore Mitochondrial Plasticity

“…In a recent report, both SS-31 and SS-20 significantly reduced oxidative stress and renal injury in rats given diatrizoate. 76 These studies highlight the number of drug-induced toxicities that appear to be mediated by mitochondrial impairment and suggest that SS-31 can significantly protect against such toxicities caused by diverse chemical compounds.…”

First‐in‐class cardiolipin‐protective compound as a therapeutic agent to restore mitochondrial bioenergetics

“…This review will concentrate on the most recent findings and those preclinical studies that have provided the rationale for clinical trials with SS‐31. In addition to studies described in detail below, SS‐31 has been reported to be beneficial for chronic kidney disease, metabolic syndrome, neurodegenerative diseases and drug‐induced mitochondrial toxicity (Petri et al ., ; Mizuguchi et al ., ; Anderson et al ., ; Yang et al ., ; Duan et al ., ; Huang et al ., ; Toyama et al ., ). It should be pointed out that SS‐31 is also referred to as MTP‐131 or Bendavia in the literature.…”

The Emerging Role of Mitochondrial Targeting in Kidney Disease

“…SS-31 pretreatment also serves a protective role against hypoxia-/reoxygenation-induced apoptosis of human renal tubular epithelial cells, partly by suppression of p66Shc (Zhao et al 2013), a gene that encodes for an adaptor protein that regulates oxidative stress and apoptosis. Moreover, intraperitoneal injections of SS-31 in rats alleviate contrast-induced AKI, primarily due to an antioxidant action (Duan et al 2013). …”