Astaxanthin ameliorates ferric nitrilotriacetate-induced renal oxidative injury in rats

Our plain-English summary of Astaxanthin ameliorates ferric nitrilotriacetate-induced renal oxidative injury in rats, by Y. Okazaki, S. Okada, S. Toyokuni (Journal of Clinical Biochemistry and Nutrition, 2017).

The study

• Authors: Y. Okazaki, S. Okada, S. Toyokuni
• Journal: Journal of Clinical Biochemistry and Nutrition
• Published: 2017;61(1):18-24
• Cited by: 6 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Daily intake of vegetables can reduce the risk of cancer and lifestyle-related diseases. However, supplementary intake of β-carotene alone has been reported to increase the risk of lung cancer in male cigarette smokers and people who were exposed to asbestos. The mechanism of the antioxidative properties of carotenoids in vivo, especially under oxidative stress conditions, still remains unclear. To investigate the antioxidant properties of dietary compounds, we examined the effects of chemically modified astaxanthin (Ax-C-8) using a rat model of ferric nitrilotriacetate (Fe-NTA)-induced renal oxidative injury. Ax-C-8 demonstrated lethally toxic effects on the rats in a dose-dependent manner. Following supplementation with Ax-C-8 (0.02%, w/w) for 30 days, the rats were euthanized 1, 4 and 24 h after injection of Fe-NTA. After 4 h, Ax-C-8 pretreatment suppressed the elevation of creatinine and blood urea nitrogen and protected the rats from renal tubular necrosis and the formation of 4-hydroxy-2-nonenal-modified proteins. After 24 h, pretreatment with Ax-C-8 maintained the renal antioxidant enzyme levels and renal tubules. Here, we demonstrate the antioxidant effects of Ax-C-8 against Fe-NTA-induced oxidative injury in rats receiving a regular diet. These data suggest that dietary intake of astaxanthin may be useful for the prevention of renal tubular oxidative damage.

In plain English

This was a laboratory experiment in male Wistar rats. It did not study people or asbestos; asbestos appears only in the background, describing an earlier beta-carotene trial. The authors tested a chemically modified form of the pigment astaxanthin, called Ax-C-8. In a safety test, the rats were given Ax-C-8 by stomach tube. At 49 mg per animal per day, 4 of 9 rats died within 5 days. At 25 mg per animal per day, 2 of 4 died within 17 days. Other rats ate 0.02% Ax-C-8 in their diet for 30 days, then received Fe-NTA, an iron compound that damages kidneys. Compared with rats given Fe-NTA without Ax-C-8, the pretreated rats had smaller rises in creatinine and blood urea nitrogen at 4 and 24 hours and less kidney tubule damage. Their antioxidant enzymes were better preserved at 24 hours. No antioxidant effect was seen at 1 hour. On a vitamin E-deficient diet with repeated Fe-NTA injections, Ax-C-8 shortened survival, more so at higher doses. The authors concluded that Ax-C-8 protects against iron-mediated kidney tubule injury in a rat model.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: animal experiment (laboratory study in rats)
• Who was studied: Male Wistar rats, 4 weeks old at purchase, studied in Japan: 21 rats in a safety test, rats on a regular diet in the Fe-NTA experiment (group sizes 4 to 6), and 28 rats on a vitamin E-deficient diet
• Exposure: Chemically modified astaxanthin (Ax-C-8). In the safety test it was given by stomach tube at 5, 25 or 49 mg per animal per day. In the main experiment it was given in the diet at 0.02% (w/w) for 30 days, followed by an injection into the abdomen of ferric nitrilotriacetate (Fe-NTA) at 9.0 mg Fe/kg body weight. A further experiment used repeated Fe-NTA injections in rats on a vitamin E-deficient diet with 0.01%, 0.02% or 0.04% Ax-C-8.
• Main results:
  • Safety test: at the high dose (49 mg/animal/day), 4 of 9 rats died within 5 days. At the medium dose (25 mg/animal/day), 2 of 4 rats died within 17 days.
  • One hour after Fe-NTA, TBARS (a marker of lipid peroxidation) rose to a similar level with and without Ax-C-8: 31.6 ± 1.35 in the vehicle + Fe-NTA group and 30.2 ± 0.86 in the Ax-C-8 + Fe-NTA group, against 11.1 ± 0.5 in untreated vehicle rats (nmol/100 mg protein). Reduced glutathione was depleted with or without Ax-C-8.
  • Serum creatinine and blood urea nitrogen rose 4 and 24 hours after Fe-NTA. Compared with rats given Fe-NTA without Ax-C-8, Ax-C-8 pretreatment suppressed these rises at both time points.
  • At 4 hours, Ax-C-8 pretreatment prevented the fall in antioxidant enzyme activities, but the differences were not statistically significant (p greater than 0.05). The exception was glutathione S-transferase, which was significantly preserved: 123.8 ± 6.09 in Ax-C-8 + Fe-NTA rats, against 110.8 ± 2.61 in vehicle + Fe-NTA rats and 137.2 ± 5.54 in vehicle rats (nmol CDNB conjugate formed/min/mg protein).
  • At 24 hours, Ax-C-8 pretreatment significantly maintained glutathione reductase, glutathione peroxidase and catalase levels after Fe-NTA.
  • At 4 hours, Fe-NTA caused acute tubular necrosis in the proximal kidney tubules. Rats pretreated with Ax-C-8 were highly protected from this injury and had significantly fewer tubules positive for HNE-modified proteins.
  • In rats on a vitamin E-deficient diet given repeated Fe-NTA injections, Ax-C-8 supplementation shortened survival in a dose-dependent manner.
  • In the vitamin E-deficient experiment, some Ax-C-8-treated rats had diarrhea. Some also had calcification inside the chest and in the digestive tract wall: 2 of 6 rats at 0.01%, 0 of 6 at 0.02%, and 1 of 6 at 0.04%.
• The authors' conclusion: The authors concluded that, for the first time, they had observed that Ax-C-8 protects against iron-mediated kidney tubule injury in a rat model. They wrote that dietary astaxanthin may be useful for preventing oxidative damage to kidney tubules. They also wrote that further study is warranted.
• Limitations the authors state:
  • The authors suggest that the vitamin E-stripped corn oil used to dissolve Ax-C-8 may have worsened tissue injury. They offer this as a possible reason why no significant protection was seen at 1 hour.
  • Only a small number of serum samples were available for the calcium analysis in the vitamin E-deficient experiment.

Topics

Medical terms in this study, explained in our Lexicon: Lung Cancer, Oxidative Stress, Necrosis, Tubule.

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