Caloric Restriction Mimetic Hydroxycitrate Mitigates Acute Nephrotoxicity via Autophagy Activation and Oxidative Stress Reduction.
| Title: | Caloric Restriction Mimetic Hydroxycitrate Mitigates Acute Nephrotoxicity via Autophagy Activation and Oxidative Stress Reduction. |
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| Authors: | Liao X; A.N. Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, 119992 Moscow, Russia.; Faculty of Bioengineering and Bioinformatics, Lomonosov Moscow State University, 119234 Moscow, Russia.; Andrianova NV; A.N. Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, 119992 Moscow, Russia.; Zorova LD; A.N. Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, 119992 Moscow, Russia.; Brezgunova AA; A.N. Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, 119992 Moscow, Russia.; Cherkesova KS; A.N. Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, 119992 Moscow, Russia.; Faculty of Biology, Lomonosov Moscow State University, 119234 Moscow, Russia.; Buyan MI; A.N. Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, 119992 Moscow, Russia.; Faculty of Bioengineering and Bioinformatics, Lomonosov Moscow State University, 119234 Moscow, Russia.; Semenovich DS; A.N. Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, 119992 Moscow, Russia.; Dalina AA; Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, 119991 Moscow, Russia.; Pevzner IB; A.N. Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, 119992 Moscow, Russia.; Jin J; Department of Nephrology, Zhejiang Provincial Hospital of Chinese Medicine, Hangzhou 310006, China.; Wang Y; Department of Nephrology, Zhejiang Provincial Hospital of Chinese Medicine, Hangzhou 310006, China.; Plotnikov EY; A.N. Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, 119992 Moscow, Russia. |
| Source: | Biomolecules [Biomolecules] 2026 Apr 04; Vol. 16 (4). Date of Electronic Publication: 2026 Apr 04. |
| Publication Type: | Journal Article |
| Language: | English |
| Journal Info: | Publisher: MDPI Country of Publication: Switzerland NLM ID: 101596414 Publication Model: Electronic Cited Medium: Internet ISSN: 2218-273X (Electronic) Linking ISSN: 2218273X NLM ISO Abbreviation: Biomolecules Subsets: MEDLINE |
| Imprint Name(s): | Original Publication: Basel, Switzerland : MDPI, 2011- |
| MeSH Terms: | Autophagy*/drug effects ; Oxidative Stress*/drug effects ; Acute Kidney Injury*/chemically induced ; Acute Kidney Injury*/drug therapy ; Acute Kidney Injury*/metabolism ; Acute Kidney Injury*/pathology ; Citrates*/pharmacology ; Caloric Restriction*; Gentamicins/adverse effects ; Gentamicins/toxicity ; Cell Survival/drug effects ; Cell Proliferation/drug effects ; Apoptosis/drug effects ; Animals ; Rats ; Male ; Rats, Sprague-Dawley ; Cell Line |
| Abstract: | Drug-induced nephrotoxicity is a leading cause of acute kidney injury (AKI) and subsequent chronic kidney disease. Nephrotoxicity often develops as a consequence of treatment with commonly prescribed aminoglycoside antibiotics, and remains a significant clinical challenge. One approach to treating AKI and its associated complications is caloric restriction or its pharmacological mimetics. This study aimed to evaluate the effects of caloric restriction mimetic hydroxycitrate (HC) in gentamicin-induced nephrotoxicity, with particular focus on the influence of treatment duration and the underlying molecular mechanisms. In vitro renal tubular epithelial cells models were used to assess HC's effects on viability, proliferation, and autophagy activation. For in vivo validation, rats with gentamicin-induced AKI received HC treatment via two distinct regimens (3-week and 7-week administration). Experiments on renal tubule cells showed that HC significantly increased cell viability and proliferation and led to the activation of autophagy. In the rat model, only the 7-week administration of HC demonstrated significantly attenuated renal dysfunction in gentamicin-induced AKI. Moreover, it reduced macrophage infiltration, increased renal cell tolerance to apoptosis, activated autophagy, and reduced oxidative stress. Thus, our results indicate that 7-week HC administration could be used as a prophylactic strategy against antibiotic nephrotoxicity, exerting its effects by promoting autophagy, resisting apoptosis, and attenuating oxidative damage. |
| Grant Information: | 21-75-30009 Russian Science Foundation |
| Contributed Indexing: | Keywords: acute kidney injury; apoptosis; autophagy; caloric restriction; caloric restriction mimetics; inflammation; mitochondria; oxidative stress |
| Substance Nomenclature: | 0 (Citrates); 0 (Gentamicins); 8W94T9026R (hydroxycitric acid) |
| Entry Date(s): | Date Created: 20260504 Date Completed: 20260504 Latest Revision: 20260507 |
| Update Code: | 20260507 |
| PubMed Central ID: | PMC13113946 |
| DOI: | 10.3390/biom16040538 |
| PMID: | 42072659 |
| Database: | MEDLINE |
Journal Article