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Comp Biochem Physiol C Toxicol Pharmacol. 2019 Mar;217:41-53. doi: 10.1016/j.cbpc.2018.11.020. Epub 2018 Nov 30.

Protective effects of alpha-ketoglutarate against aluminum toxicity in Drosophila melanogaster.

Author information

1
Department of Biochemistry and Biotechnology, Vasyl Stefanyk Precarpathian National University, 57 Shevchenko Str., Ivano-Frankivsk 76018, Ukraine. Electronic address: bayliak@ukr.net.
2
Department of Biochemistry and Biotechnology, Vasyl Stefanyk Precarpathian National University, 57 Shevchenko Str., Ivano-Frankivsk 76018, Ukraine.
3
Department of Biochemistry and Biotechnology, Vasyl Stefanyk Precarpathian National University, 57 Shevchenko Str., Ivano-Frankivsk 76018, Ukraine. Electronic address: dmytro.hospodarov@pu.if.ua.
4
Department of Materials Science and Advanced Technologies, Vasyl Stefanyk Precarpathian National University, 57 Shevchenko Str., Ivano-Frankivsk 76018, Ukraine.
5
Institute of Biochemistry, Carleton University, 1125 Colonel By Drive, Ottawa, Ontario K1S 5B6, Canada.
6
Department of Biochemistry and Biotechnology, Vasyl Stefanyk Precarpathian National University, 57 Shevchenko Str., Ivano-Frankivsk 76018, Ukraine. Electronic address: lushchak@pu.if.ua.

Abstract

In recent years, Drosophila melanogaster has emerged as a model for studies on aluminum toxicity. The current study aimed to disclose the mechanisms of aluminum toxicity in D. melanogaster at larval and adult stages and examined the potential protective effects of dietary alpha-ketoglutarate (AKG). Flies were reared on food containing 10 mM AlCl3, 10 mM AKG or both additives. Rearing on an AlCl3-containing diet induced behavioral defects, and decreased fecundity and long-term survival of female flies. The addition of dietary AKG did not ameliorate locomotor and taste behavior defects or the higher sensitivity to oxidative stress, but improved heat stress resistance, egg-laying capability and survival of females treated with AlCl3. Metabolic effects of AlCl3 exposure on flies included an imbalance of metal content, decreased glucose levels, increased free iron and storage triacylglyceride (TAG) levels, mitochondria dysfunction, and the development of oxidative stress. Dietary AKG did not prevent AlCl3 effects on glucose and TAG, but improved metal homeostasis, inhibited the increase in free Fe and restored the functional activity of iron-containing enzymes such as aconitase. In addition, AKG decreased the intensity of oxidative stress seen in AlCl3-reared adult flies, probably due to inhibition of iron mobilization. The results show that AKG is not a full antidote against Al toxicity but is able to relieve multiple metabolic effects of high aluminum. Furthermore, the modulating ability of AKG can clearly be helpful in exploring the molecular mechanisms of Al toxicity.

KEYWORDS:

Antioxidant; Fecundity; Mitochondrial dysfunction; Oxidative stress; Pupation; Survival; Triacylglycerides

PMID:
30508642
DOI:
10.1016/j.cbpc.2018.11.020
[Indexed for MEDLINE]

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