Effect of sodium thiosulfate on preventing renal ischemia-reperfusion injury in high-fat diet-fed rats: the role of renal mitochondrial quality

• Published in: Biological research Vol. 58; no. 1; pp. 56 - 14
• Main Authors: Prem, Priyanka N., Kurian, Gino A.
• Format: Journal Article
• Language: English
• Published: England BioMed Central Ltd 18.08.2025; BioMed Central; BMC
• Subjects: Anti-inflammatory drugs; Antioxidants; Cyanides; Ethylenediaminetetraacetic acid; Genes; High fat diet; Ischemia; Mitochondria; Oxidative stress; Physiological aspects; Prevention; Renal ischemia reperfusion; Sodium thiosulfate; South Dakota; Oxidative stress; Mitochondria; Sodium thiosulfate; Renal ischemia reperfusion; High fat diet
• ISSN: 0717-6287; 0716-9760; 0717-6287
• DOI: 10.1186/s40659-025-00636-z

Sodium Thiosulfate (STS), a clinically approved agent for cyanide poisoning and vascular calcification, possesses antioxidant, anti-inflammatory, mitochondrial preservation, and metal chelation capabilities, rendering it a promising candidate for managing ischemia-reperfusion (IR) injury. The detrimental impact of high-fat diets (HD) on the outcomes of IR during renal surgeries is well-documented. However, the potential of STS to ameliorate renal IR injury in rat fed with high fat diet is not known. Male Wistar rats were fed a standard diet (SD) or a high-fat diet (HD) for 16 weeks before undergoing an IR protocol (45 min of ischemia followed by 24 h of reperfusion). STS (10 mg/kg) was administered 30 min before IR. STS effectively mitigated IR-induced physiological decline and tissue damage in SD rats but was less effective in HD rats. To explore this difference, we measured renal mitochondrial quality. STS improved mitochondrial bioenergetics, balanced mitochondrial dynamics, and increased mitochondrial copy number in SD-IR rats more than in HD-IR rats. Additionally, STS significantly reduced oxidative stress and upregulated Pgc-1α, Polg, and Tfam genes in SD-IR rats but had a lesser effect in HD-IR rats. The 16-week HD significantly reduced renal mitochondrial quality at the basal level, hindering STS-mediated protection. These findings highlight the efficacy of STS in managing renal IR and emphasize the need for nutritional support to restore mitochondrial function in high-fat diet subjects.