Therapeutic effects of atorvastatin on doxorubicin‐induced hepatotoxicity in rats via antioxidative damage, anti‐inflammatory, and anti‐lipotoxicity

Wu, Yongchao; Wang, Kexin; Ma, Xindi; Wang, Chu-Chu; Chen, Nannan; Xiong, Chen; Li, Junxia; Su, Suwen

doi:10.1002/jbt.23329

Cited by 5 publications

(1 citation statement)

References 37 publications

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“…In a separate rat model of nonalcoholic fatty liver disease (NAFLD), atorvastatin had antioxidant and anti-inflammatory effects, preventing development of biochemical and histologic disease 39 . Similarly, in a doxorubicin-induced hepatotoxicity model in rats, atorvastatin prevented oxidative stress, inhibited NF-kB and IL-1 signaling, and accelerated hepatic lipid metabolism 40 . Atorvastatin also reduced fibrosis in a rat carbon tetrachloride model of liver fibrosis 41 .…”

Section: Discussionmentioning

confidence: 91%

Inflammation drives pathogenesis of early intestinal failure-associated liver disease

Fligor,

Tsikis,

Hirsch

et al. 2024

Sci Rep

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Patients with intestinal failure who receive long-term parenteral nutrition (PN) often develop intestinal failure-associated liver disease (IFALD). Although there are identified risk factors, the early pathogenesis is poorly understood and treatment options are limited. Here, we perform a transcriptomic analysis of liver tissue in a large animal IFALD model to generate mechanistic insights and identify therapeutic targets. Preterm Yorkshire piglets were provided PN or bottle-fed with sow-milk replacer for 14 days. Compared to bottle-fed controls, piglets receiving PN developed biochemical cholestasis by day of life 15 (total bilirubin 0.2 vs. 2.9 mg/dL, P = 0.01). RNA-Seq of liver tissue was performed. Ingenuity Pathway Analysis identified 747 differentially expressed genes (343 upregulated and 404 downregulated) with an adjusted P < 0.05 and a fold-change of > |1|. Enriched canonical pathways were identified, demonstrating broad activation of inflammatory pathways and inhibition of cell cycle progression. Potential therapeutics including infliximab, glucocorticoids, statins, and obeticholic acid were identified as predicted upstream master regulators that may reverse the PN-induced gene dysregulation. The early driver of IFALD in neonates may be inflammation with an immature liver; identified therapeutics that target the inflammatory response in the liver should be investigated as potential treatments.

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Section: Discussionmentioning

confidence: 91%

Inflammation drives pathogenesis of early intestinal failure-associated liver disease

Fligor,

Tsikis,

Hirsch

et al. 2024

Sci Rep

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Betaine alleviates doxorubicin‐induced nephrotoxicity by preventing oxidative insults, inflammation, and fibrosis through the modulation of Nrf2/HO−1/NLRP3 and TGF‐β expression

Patel,

Yadav,

Singh

et al. 2023

J Biochem & Molecular Tox

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Doxorubicin (Dox) is an anthracycline antibiotic used to treat various cancers and shows severe toxicity in multiple organ systems, including kidneys. Evidence shows that betaine's antioxidant and anti‐inflammatory properties could prevent the onset of several disorders. Hence, the present study aims to investigate the therapeutic potential of betaine on Dox‐induced nephrotoxicity (DIN). Nephrotoxicity was induced in male Sprague Dawley rats using Dox at a dose of 4 mg/kg (cumulative dose: 20 mg/kg) by the intraperitoneal route and cotreated with betaine through oral gavage (200 and 400 mg/kg) for 28 days. At the end of the experiment, biochemical, oxidative stress parameters, histopathology, and qRT‐PCR were performed. DIN was indicated by elevated serum creatinine, urea, and decreased albumin levels representing kidney damage; the histopathological lesions (increased capsular space, renal tubule damage, and fibrosis) in renal tissues supported these biochemical findings. Interestingly, betaine treatment improves these alterations in Dox‐treated rats. Further, betaine treatment decreases the lipid peroxidation and nitrite concentration and increases the superoxide dismutases and catalase enzyme concentration in Dox‐treated rats. Fascinatingly, at the molecular level, DIN in rats shows upregulation of the Nrf2/HO‐1 gene, while betaine treatment attenuated its expression along with the downregulation of inflammatory genes (NLRP3, TLR‐4, TNF‐α, and IL‐6) and fibrosis‐related genes (TGF‐β and Acta2) expression in Dox‐treated rats. These results showed that betaine has reno‐protective properties by reducing inflammatory and fibrotic mediators and enhancing antioxidant capacity in the renal tissue of rats treated with Dox. We believe betaine can be exploited as a dietary supplement to attenuate DIN.

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Doxorubicin-mediated cardiac dysfunction: Revisiting molecular interactions, pharmacological compounds and (nano)theranostic platforms

2023

Environmental Research

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Therapeutic effects of atorvastatin on doxorubicin‐induced hepatotoxicity in rats via antioxidative damage, anti‐inflammatory, and anti‐lipotoxicity

Cited by 5 publications

References 37 publications

Inflammation drives pathogenesis of early intestinal failure-associated liver disease

Inflammation drives pathogenesis of early intestinal failure-associated liver disease

Betaine alleviates doxorubicin‐induced nephrotoxicity by preventing oxidative insults, inflammation, and fibrosis through the modulation of Nrf2/HO−1/NLRP3 and TGF‐β expression

Doxorubicin-mediated cardiac dysfunction: Revisiting molecular interactions, pharmacological compounds and (nano)theranostic platforms

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