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Nephrotoxicity and its prevention by taurine in tamoxifen induced oxidative stress in mice
Heena Tabassum1, Suhel Parvez, Hasibur Rehman
1Immunotoxicology Laboratory, Department of Medical Elementology and Toxicology, Jamia Hamdard (Hamdard University), New Delhi, India.
Abstract:
Tamoxifen (TAM) is an anti-neoplastic drug used for the treatment of breast cancer. It decreases the hexose monophosphate shunt and thereby increasing the incidence of oxidative stress in cells leading to tissue injury. The present study was undertaken to investigate modulatory effects of taurine on the nephrotoxicity of TAM with special reference to protection against disruption of nonenzymatic and enzymatic antioxidants. Oxidative stress was measured by renal lipid peroxidation (LPO) level, protein carbonyl (PC) content, reduced glutathione (GSH), activities of phase I and II drug metabolizing and antioxidant enzymes. TAM treatment resulted in a significant (P < 0.001) increase in LPO in kidney tissues as compared to control, while taurine pretreatment showed a significant decrease (P < 0.01) in the LPO in kidneys when compared with the TAM-treated group. Taurine + TAM group animals showed restoration in the level of cytochrome P450 content, activities of glutathione metabolizing enzymes viz., glutathione-S-transferase, glutathione peroxidase, glutathione reductase, glucose-6-phosphate dehydrogenase. Pretreatment of animals with taurine markedly attenuated, PC content, restored the depleted nonenzymatic and enzymatic antioxidants. These results clearly demonstrate the role of oxidative stress, and suggest a protective effect of taurine on TAM-induced nephrotoxicity in mice.
Insights
Taurine protects against tamoxifen-induced kidney damage by reducing oxidative stress. This study shows taurine helps restore antioxidant levels disrupted by tamoxifen treatment.
Area of Science:
- Biochemistry
- Toxicology
- Pharmacology
Background:
- Tamoxifen (TAM) is an anti-neoplastic drug for breast cancer.
- TAM can induce oxidative stress and tissue injury by affecting the hexose monophosphate shunt.
- Kidney toxicity (nephrotoxicity) is a potential side effect of TAM treatment.
Purpose of the Study:
- To investigate the protective effects of taurine against tamoxifen-induced nephrotoxicity.
- To examine how taurine modulates nonenzymatic and enzymatic antioxidants during TAM treatment.
- To assess the impact of taurine on oxidative stress markers in kidney tissue.
Main Methods:
- Mice were treated with tamoxifen (TAM) and/or taurine.
- Kidney tissues were analyzed for lipid peroxidation (LPO), protein carbonyl (PC) content, and reduced glutathione (GSH).
- Activities of phase I and II drug metabolizing and antioxidant enzymes were measured.
Main Results:
- TAM treatment significantly increased LPO in kidney tissues.
- Taurine pretreatment significantly decreased LPO compared to TAM-treated group.
- Taurine restored levels of cytochrome P450, glutathione metabolizing enzymes, and glucose-6-phosphate dehydrogenase.
- Taurine attenuated PC content and restored depleted antioxidants.
Conclusions:
- Tamoxifen-induced nephrotoxicity is mediated by oxidative stress.
- Taurine exhibits a protective effect against tamoxifen-induced kidney damage.
- Taurine helps maintain antioxidant balance during tamoxifen therapy.
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