ArticleAntibiotics (Basel, Switzerland)2023
Shikonin Alleviates Gentamicin-Induced Renal Injury in Rats by Targeting Renal Endocytosis, SIRT1/Nrf2/HO-1, TLR-4/NF-κB/MAPK, and PI3K/Akt Cascades.
Article in Antibiotics (Basel, Switzerland), 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
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Who cites it
9 citing papers in PubMed, 21 citations in OpenAlex.
- LC-ESI-TOF-MS profiling and protective effects of Psidium cattleianum extract against gentamicin-induced nephrotoxicity in rats via Nrf2/HO-1 and caspase-dependent pathway.Saudi pharmaceutical journal : SPJ : the official publication of the Saudi Pharmaceutical Society · 2026Article
- Febuxostat attenuates chronic kidney disease induced by adenine in rats: role of TLR4/NF-κB/NLRP3/Caspase1/IL-1β pathway.Inflammopharmacology · 2026Article
- Effects of Peptides and Bioactive Peptides on Acute Kidney Injury: A Review Study.Iranian biomedical journal · 2025Review
- Shikonin attenuates blood-brain barrier injury and oxidative stress in rats with subarachnoid hemorrhage by activating Sirt1/Nrf2/HO-1 signaling.The Korean journal of physiology & pharmacology : official journal of the Korean Physiological Society and the Korean Society of Pharmacology · 2025Article
- Podocyte SIRPα reduction in diabetic nephropathy aggravates podocyte injury by promoting pyruvate kinase M2 nuclear translocation.Redox biology · 2024Article
- Combined effect of naringin and adipose tissue-derived mesenchymal stem cell on cisplatin nephrotoxicity through Sirtuin1/Nrf-2/HO-1 signaling pathway: a promising nephroprotective candidate.Cell and tissue research · 2024Article
- Based on network pharmacology and molecular docking to explore the potential mechanism of shikonin in periodontitis.BMC oral health · 2024Article
- Targeting pyruvate kinase M2 for the treatment of kidney disease.Frontiers in pharmacology · 2024Review
- Pharmacological Effects of Shikonin and Its Potential in Skin Repair: A Review.Molecules (Basel, Switzerland) · 2023Review
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Authors and funding
4 authors at 3 institutions in 3 countries.
Funding
Abstract
Gentamicin causes kidney injury due to its accumulation in proximal tubule epithelial cells via the megalin/cubilin/CLC-5 complex. Recently, shikonin has been shown to have potential anti-inflammatory, antioxidant, antimicrobial, and chloride channel-inhibiting effects. The current study investigated the alleviation of gentamicin-induced renal injury by shikonin while preserving its bactericidal effect. Nine-week-old Wistar rats were administered 6.25, 12.5, and 25 mg/kg/day shikonin orally, one hour after the i.p. injection of 100 mg/kg/day gentamicin for seven days. Shikonin significantly and dose-dependently alleviated gentamicin-induced renal injury, as revealed by restoring normal kidney function and histological architecture. Furthermore, shikonin restored renal endocytic function, as indicated by suppressing the elevated renal megalin, cubilin, and CLC-5 and enhancing the reduced NHE3 levels and mRNA expressions induced by gentamicin. These potentials could be attributed to the modulation of the renal SIRT1/Nrf2/HO-1, TLR-4/NF-κB/MAPK, and PI3K/Akt cascades, which enhanced the renal antioxidant system and suppressed renal inflammation and apoptosis, as indicated by enhancements of SIRT1, Nrf2, HO-1, GSH, SOD, TAC, Iκb-α, Bcl-2, PI3K, and Akt levels and mRNA expressions, with reduction of TLR-4, NF-κB, MAPK, IL-1β, TNF-α, MDA, iNOS, NO, cytochrome c, caspase-3, Bax levels, and Bax/Bcl-2 ratio. Therefore, shikonin is a promising therapeutic agent for alleviating gentamicin-induced renal injury.
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