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Updated: Apr 23, 2026
Acute Kidney Injury Model Induced by Cisplatin in Adult Zebrafish
Published on: May 15, 2021
Tempol, a superoxide dismutase mimetic agent, ameliorates cisplatin-induced nephrotoxicity through alleviation of
Lamiaa A Ahmed1, Nagwa I Shehata2, Noha F Abdelkader1
1Department of Pharmacology and Toxicology, Faculty of Pharmacy, Cairo University, Cairo, Egypt.
Background:
Mitochondrial dysfunction is a crucial mechanism by which cisplatin, a potent chemotherapeutic agent, causes nephrotoxicity where mitochondrial electron transport complexes are shifted mostly toward imbalanced reactive oxygen species versus energy production. In the present study, the protective role of tempol, a membrane-permeable superoxide dismutase mimetic agent, was evaluated on mitochondrial dysfunction and the subsequent damage induced by cisplatin nephrotoxicity in mice.
Methods And Findings:
Nephrotoxicity was assessed 72 h after a single i.p. injection of cisplatin (25 mg/kg) with or without oral administration of tempol (100 mg/kg/day). Serum creatinine and urea as well as glucosuria and proteinuria were evaluated. Both kidneys were isolated for estimation of oxidative stress markers, adenosine triphosphate (ATP) content and caspase-3 activity. Moreover, mitochondrial oxidative phosphorylation capacity, complexes I-IV activities and mitochondrial nitric oxide synthase (mNOS) protein expression were measured along with histological examinations of renal tubular damage and mitochondrial ultrastructural changes. Tempol was effective against cisplatin-induced elevation of serum creatinine and urea as well as glucosuria and proteinuria. Moreover, pretreatment with tempol notably inhibited cisplatin-induced oxidative stress and disruption of mitochondrial function by restoring mitochondrial oxidative phosphorylation, complexes I and III activities, mNOS protein expression and ATP content. Tempol also provided significant protection against apoptosis, tubular damage and mitochondrial ultrastructural changes. Interestingly, tempol did not interfere with the cytotoxic effect of cisplatin against the growth of solid Ehrlich carcinoma.
Conclusion:
This study highlights the potential role of tempol in inhibiting cisplatin-induced nephrotoxicity without affecting its antitumor activity via amelioration of oxidative stress and mitochondrial dysfunction.
Insights
Tempol protects against cisplatin-induced kidney damage by reducing oxidative stress and improving mitochondrial function. This protective effect occurs without compromising cisplatin's anti-cancer efficacy.
Area of Science:
- Biochemistry
- Pharmacology
- Nephrology
Background:
- Cisplatin, a chemotherapy drug, causes kidney toxicity (nephrotoxicity) by disrupting mitochondrial function and increasing oxidative stress.
- Mitochondrial dysfunction involves an imbalance in reactive oxygen species production and energy generation within the electron transport chain.
Purpose of the Study:
- To evaluate the protective role of tempol, a superoxide dismutase mimetic, against cisplatin-induced nephrotoxicity in mice.
- To investigate tempol's effects on mitochondrial dysfunction, oxidative stress, and kidney damage caused by cisplatin.
Main Methods:
- Mice received cisplatin with or without tempol.
- Kidney function was assessed via serum creatinine, urea, glucosuria, and proteinuria.
- Oxidative stress markers, ATP content, caspase-3 activity, mitochondrial function (oxidative phosphorylation, complex activities), and mNOS expression were measured.
- Histological and ultrastructural analyses of kidney tissue were performed.
Main Results:
- Tempol significantly reduced cisplatin-induced increases in serum creatinine, urea, glucosuria, and proteinuria.
- Tempol mitigated cisplatin-induced oxidative stress and restored mitochondrial function, including ATP levels and mitochondrial complex activities.
- Tempol protected against apoptosis, renal tubular damage, and mitochondrial ultrastructural alterations.
- Tempol did not interfere with cisplatin's anti-cancer activity against Ehrlich carcinoma.
Conclusions:
- Tempol demonstrates a protective effect against cisplatin-induced nephrotoxicity.
- Tempol ameliorates kidney damage by reducing oxidative stress and improving mitochondrial function.
- Tempol offers a potential therapeutic strategy to mitigate chemotherapy side effects without reducing efficacy.
