Renoprotective Effect of Taxifolin in Paracetamol-Induced Nephrotoxicity: Emerging Evidence from an Animal Model

Topal, İsmail; Özdamar, Mustafa Yaşar; ÇATAKLI>, Tülin; Malkoç, Ismail; Hacımüftüoğlu, Ahmet; Mamoulakis, Charalampos; Tsatsakis, Aristidis; Tsarouhas, Konstantinos; Tsitsimpikou, Christina; Taghizadehghalehjoughi, Ali̇

doi:10.3390/jcm12030876

Cited by 4 publications

(2 citation statements)

References 56 publications

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“…TEE exhibited a hepatoprotective effect and decreased the levels of ALT and AST to within the normal physiological range. Cd also induced nephrotoxicity in the treatment group, leading to elevated levels of blood urea nitrogen and serum creatinine, similar to previous studies reporting the nephrotoxic effects of this metal. , TEE, due to its nephron-protective effect, modulated the levels of blood urea nitrogen and serum creatinine . Gene expression analysis of critical genes linked to glucose metabolism, insulin tolerance, and sensitivity was also conducted.…”

Section: Discussionsupporting

confidence: 92%

“…38,39 TEE, due to its nephron-protective effect, modulated the levels of blood urea nitrogen and serum creatinine. 40 Gene expression analysis of critical genes linked to glucose metabolism, insulin tolerance, and sensitivity was also conducted. CdCl 2 administration downregulated the expression of IGF-1, a crucial factor regulating insulin release.…”

Section: ■ Discussionmentioning

confidence: 99%

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Modulation of Metabolic Pathways and Protection against Cadmium-Induced Disruptions with Taxifolin-Enriched Extract

Khalid,

Akash,

Rehman

et al. 2024

ACS Omega

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Cadmium, a ubiquitous environmental pollutant, has been implicated in the disruption of various metabolic pathways, contributing to the development of insulin resistance, glucose intolerance, and associated metabolic disorders. This study aimed to investigate the cadmium chloride (CdCl 2 ) exposure on metabolic pathways and to assess the potential therapeutic efficacy of the taxifolin-enriched extract in mitigating these disruptions by modulating biochemical pathways. Taxifolin-enriched extract (TEE) was prepared from Pinus roxburghii bark using a green extraction method. About 60 Wistar albino rats were divided into six groups: the control group (n = 10), the CdCl 2 group (30 mg/kg) (n = 10), and four groups (each comprises n = 10) treated with 30 mg/kg CdCl 2 in combination with metformin (100 mg/kg), ascorbic acid, taxifolin (30 mg/kg), and TEE (30 mg/kg), respectively. After the treatment period of 1 month, a comprehensive assessment of metabolic biomarkers and gene expressions that regulate the metabolism of carbohydrates and lipids was conducted to evaluate the impact of CdCl 2 exposure and the potential protective effects of TEE. The results revealed that CdCl 2 exposure significantly increased (P < 0.001) serum levels of α-glucosidase, α-amylase, insulin, G6PC, hexokinases, TGs, LDL, HMG-CoA reductase, and pro-inflammatory cytokines such as IL-6 and TNF-α. Conversely, CdCl 2 exposure led to a reduction in HDL, antioxidant enzyme levels, phosphofructokinases, and glucose-6-phosphatase dehydrogenase. However, the administration of TEE alongside CdCl 2 substantially mitigated (P < 0.001) these fluctuations in metabolic and inflammatory biomarker levels induced by CdCl 2 exposure. Both TEE and taxifolin treatment effectively lowered the elevated levels of α-amylase, α-glucosidase, G6PC, insulin, TGs, HMG-CoA reductase, leptin, ALT, AST, blood urea nitrogen, creatinine, and pro-inflammatory cytokines while simultaneously enhancing levels of HDL cholesterol and antioxidant enzymes. Moreover, CdCl 2 exposure suppressed mRNA expression of critical metabolic biomarkers such as glucose transporter 2 (GLUT2), insulin-like growth factor 1 (IGF-1), lactate dehydrogenase, and HMG-CoA lyases while upregulating the mRNA expression of angiotensin receptor 2 and vasopressin, key metabolic biomarkers involved in glucose metabolism and insulin regulation. TEE demonstrated the potential to restore normal metabolic functions and reduce the adverse impacts caused by CdCl 2 exposure by mitigating disturbances in several metabolic pathways and restoring gene expression of critical metabolic biomarkers related to glucose metabolism and insulin regulation. Nevertheless, further investigation is warranted to comprehensively understand the underlying mechanisms and optimize the appropriate dosage and duration of TEE treatment for achieving the most effective therapeutic outcomes.

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Section: Discussionsupporting

confidence: 92%

Section: ■ Discussionmentioning

confidence: 99%

Modulation of Metabolic Pathways and Protection against Cadmium-Induced Disruptions with Taxifolin-Enriched Extract

Khalid,

Akash,

Rehman

et al. 2024

ACS Omega

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Antioxidant, hepatoprotective & nephroprotective potential of a novel synthetic compound 2′, 3′-dihydroxybenzylidene in paracetamol intoxicated rats

Attaullah,

Ullah,

Hussain

et al. 2023

Heliyon

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Effects of Thymoquinone Nanoparticles on Paracetamol-Induced Nephrotoxicity by Mitigating Oxidative Stress and Inflammation in Rats

Alaryani

2024

Annals of Animal Science

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A common and efficient analgesic-antipyretic medication for a variety of syndromes is paracetamol (PAR). The use of PAR was associated with acute kidney injury and other side effects, and its hazardous effects were influenced by oxidative stress and inflammation. Black seed oil's primary active ingredient, thymoquinone (TQ), has anti-inflammatory, immunomodulatory, and antioxidant properties. A few animal models for drug-induced nephrotoxicity described promising outcomes of its renoprotective action. The main goal of this work was to evaluate TQ nanoparticles' (TQNP) powerful renoprotective properties in a rat model of nephrotoxicity caused by PAR. Three groups of eight rats each were assigned; group one (the control group, CON) was given gavaged normal saline. Group 2 (PAR group, PAR) received 600 mg/kg of gavaged PAR diluted in regular saline. One hour after PAR delivery, group 3 (the TQNP group) received TQNP 0.5 mg/kg via oral administration. In rat kidney tissues, PAR resulted in renal damage, a rise in blood urea nitrogen (BUN), creatinine, cystatin C (CYC), myeloperoxidase, protein carbonyl (PC), malondialdehyde (MDA), and a decrease in nitric oxide and cellular antioxidants. In rats given PAR, TQNP effectively reduced renal damage, lowered serum levels of creatinine, BUN, and CYC, and improved oxidative stress (MDA, MYO, and PC) and inflammatory markers (TNFα and IFN-γ). TQNP treatment resulted in modestly dilated/congested blood vessels in the renal tissues of PAR. The TQNP's reno-protective action is an effective preventative against PAR-induced nephrotoxicity, primarily by enhancing cellular defense mechanisms and reducing inflammatory and oxidative indicators in a rat model. However, additional research and clinical trials should be needed for testing in future studies.

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Renoprotective Effect of Taxifolin in Paracetamol-Induced Nephrotoxicity: Emerging Evidence from an Animal Model

Cited by 4 publications

References 56 publications

Modulation of Metabolic Pathways and Protection against Cadmium-Induced Disruptions with Taxifolin-Enriched Extract

Modulation of Metabolic Pathways and Protection against Cadmium-Induced Disruptions with Taxifolin-Enriched Extract

Antioxidant, hepatoprotective & nephroprotective potential of a novel synthetic compound 2′, 3′-dihydroxybenzylidene in paracetamol intoxicated rats

Effects of Thymoquinone Nanoparticles on Paracetamol-Induced Nephrotoxicity by Mitigating Oxidative Stress and Inflammation in Rats

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