Dataset Information

Taurine Protects Doxorubicin-Induced Hepatotoxicity via Its Membrane-Stabilizing Effect in Rats.

ABSTRACT:

Background

Doxorubicin (dox) is a chemotherapeutic agent widely used against various tumors. However, the clinical use of this agent is limited due to various organ toxicities. Taurine is an intracellular free β-amino acid with antioxidant properties. The present study investigated the protective mechanism of taurine on dox-induced hepatotoxicity.

Methods

In total, 31 male Sprague-Dawley rats were used in the study. The control group received intraperitoneal (i.p.) 0.9% NaCl alone for 14 days; the taurine (Tau) group received i.p. taurine 150 mg/kg body weight/day for 14 days; the dox group received dox on days 12, 13, and 14 at a cumulative dose of 25 mg/kg body weight/3 days; and the tau+dox group received taurine and dox together at the same dose and through the same route. On day 15, biochemical evaluations were performed on blood samples taken from the left ventricle followed by histological examinations on liver samples.

Results

Dox was found to increase liver function enzymes and tissue protein carbonyl levels, causing congestion and tissue damage, thereby leading to dysfunction. Tau was found to histologically preserve the liver morphology without showing any corrective effect on oxidative stress parameters. These findings suggest that the membrane-stabilizing effect of taurine may be more effective than its radical scavenging activity in preventing dox-induced toxicity.

Conclusion

Taurine can prevent doxorubicin-induced hepatotoxicity through non-antioxidant pathways.

SUBMITTER: Gedikli E

PROVIDER: S-EPMC10608465 | biostudies-literature | 2023 Oct

REPOSITORIES: biostudies-literature

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Publications

Taurine Protects Doxorubicin-Induced Hepatotoxicity via Its Membrane-Stabilizing Effect in Rats.

Gedikli Esra E Barış Veysel Özgür VÖ Yersal Nilgün N Dinçsoy Adnan Berk AB Müftüoğlu Sevda Fatma SF Erdem Ayşen A

Life (Basel, Switzerland) 20231009 10

<h4>Background</h4>Doxorubicin (dox) is a chemotherapeutic agent widely used against various tumors. However, the clinical use of this agent is limited due to various organ toxicities. Taurine is an intracellular free β-amino acid with antioxidant properties. The present study investigated the protective mechanism of taurine on dox-induced hepatotoxicity.<h4>Methods</h4>In total, 31 male Sprague-Dawley rats were used in the study. The control group received intraperitoneal (i.p.) 0.9% NaCl alone ...[more]

PMID: 37895413

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Project description:Glomerular podocytes are highly differentiated cells that are key components of the kidney filtration units. The podocyte cytoskeleton builds the basis for the dynamic podocyte cytoarchitecture and plays a central role for proper podocyte function. Recent studies implicate that immunosuppressive agents including the mTOR-inhibitor everolimus have a protective role directly on the stability of the podocyte cytoskeleton. To elucidate mechanisms underlying mTOR-inhibitor mediated cytoskeletal rearrangements, we carried out microarray gene expression studies to identify target genes and corresponding pathways in response to everolimus. We analyzed the effect of everolimus in a puromycin aminonucleoside experimental in vitro model of podocyte injury. Upon treatment with puromycin aminonucleoside, microarray analysis revealed gene clusters involving cytoskeletal-associated pathways, adhesion, migration and extracellular matrix composition to be affected. Everolimus is capable of protecting podocytes from injury, both on the transcriptome and protein level. Rescued genes included TUBB2B and DCDC2, both involved in microtubule structure formation in neuronal cells but not identified in podocytes so far. Confirming gene expression data, Western-blot analysis in cultured podocytes showed an increase of TUBB2B and DCDC2 protein after everolimus treatment, and immunohistochemistry in healthy control kidneys confirmed a podocyte-specific expression. Microtubule-inhibitor experiments led to a maldistribution of TUBB2B and DCDC2 as well as an aberrant reorganization of the actin cytoskeleton. Tubb2bbrdp/brdp mice showed a delay in glomerular podocyte and capillary development. Taken together, our study suggests that off-target, non-immune mediated effects of the mTOR-inhibitor everolimus on the podocyte cytoskeleton might involve regulation of microtubules, revealing a potential novel role of TUBB2B and DCDC2 in glomerular podocyte development We analyzed the effect of everolimus on gene expression in a puromycin aminonucleoside experimental in vitro model of podocyte injury using microarrays

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Dataset Information

Taurine Protects Doxorubicin-Induced Hepatotoxicity via Its Membrane-Stabilizing Effect in Rats.

Background

Methods

Results

Conclusion

Publications

Taurine Protects Doxorubicin-Induced Hepatotoxicity via Its Membrane-Stabilizing Effect in Rats.

Similar Datasets

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