Related Experiment Video

Updated: May 24, 2025

Acute Kidney Injury Model Induced by Cisplatin in Adult Zebrafish
13:25

Acute Kidney Injury Model Induced by Cisplatin in Adult Zebrafish

Published on: May 15, 2021

5.6K

Both carvedilol and cimetidine alleviate cisplatin-induced nephrotoxicity via downregulating OCT2

Huan Wu1, Yichun Ning2, Zhaoxing Sun1

  • 1Department of Nephrology, Zhongshan Hospital, Fudan University, Shanghai, China; Shanghai Key Laboratory of Kidney and Blood Purification, Shanghai, China.

Biochimica Et Biophysica Acta. Molecular Basis of Disease
|March 5, 2025
PubMed
Abstract

Insights

Carvedilol and cimetidine protect against cisplatin-induced acute kidney injury (Cis-AKI) by inhibiting OCT2. These drugs reduce kidney damage without affecting cisplatin's anti-tumor efficacy.

Area of Science:

  • Nephrology
  • Pharmacology
  • Oncology

Background:

  • Cisplatin chemotherapy causes severe nephrotoxicity, limiting its use.
  • Organic cation transporter 2 (OCT2) plays a role in cisplatin uptake by the kidneys.
  • Effective pharmacological treatments for cisplatin-induced acute kidney injury (Cis-AKI) are lacking.

Purpose of the Study:

  • To identify existing drugs that can prevent Cis-AKI by inhibiting OCT2.
  • To evaluate the protective effects of candidate drugs on kidney cells and in vivo models.
  • To assess if these drugs preserve cisplatin's anti-tumor activity.

Main Methods:

  • Examined OCT2 mRNA levels in patient-derived cells and kidney organoids.
  • Screened FDA-approved drugs for OCT2 inhibition and Cis-AKI protective effects.
  • Assessed drug impact on OCT2 expression, cisplatin uptake, apoptosis, and anti-tumor activity in cellular and animal models.

Main Results:

  • Elevated OCT2 mRNA levels were observed in Cis-AKI patient cells.
  • Overexpression of OCT2 worsened cisplatin-induced kidney injury.
  • Carvedilol and cimetidine were identified as potent OCT2 inhibitors.
  • These drugs reduced cisplatin uptake and apoptosis in kidney cells without compromising anti-tumor effects.

Conclusions:

  • Carvedilol and cimetidine demonstrate protective effects against Cis-AKI via OCT2 inhibition.
  • These drugs offer a potential strategy to mitigate cisplatin nephrotoxicity.
  • The identified drugs maintain cisplatin's efficacy against cancer cells.
Keywords:
CarvedilolCimetidineCisplatin-induced acute kidney injury (Cis-AKI)Drug screeningKidney organoidsThe organic cation transporter 2 (OCT2)

More Related Videos

Assessment of Mitochondrial Functions and Cell Viability in Renal Cells Overexpressing Protein Kinase C Isozymes15:43

Assessment of Mitochondrial Functions and Cell Viability in Renal Cells Overexpressing Protein Kinase C Isozymes

Published on: January 7, 2013

18.1K
Trans-Tympanic Drug Delivery for the Treatment of Ototoxicity09:52

Trans-Tympanic Drug Delivery for the Treatment of Ototoxicity

Published on: March 16, 2018

9.3K

Related Concept Videos

Inhibition of Cdk Activity02:34

Inhibition of Cdk Activity

The orderly progression of the cell cycle depends on the activation of Cdk protein by binding to its cyclin partner. However, the cell cycle must be restricted when undergoing abnormal changes. Most cancers correlate to the deregulated cell cycle, and since Cdks are a central component of the cell cycle, Cdk inhibitors are extensively studied to develop anticancer agents. For instance, cyclin D associates with several Cdks, such as Cdk 4/6, to form an active complex. The cyclin D-Cdk4/6 complex...
4.6K
Chemotherapy-Induced Nausea and Vomiting: 5-HT3 Receptor Antagonists01:27

Chemotherapy-Induced Nausea and Vomiting: 5-HT3 Receptor Antagonists

5-HT3 receptor antagonists, such as dolasetron, granisetron (Kytril), ondansetron (Zofran), and palonosetron (Axoli), are crucial in managing chemotherapy-induced nausea and vomiting (CINV) and postoperative nausea. These drugs selectively block 5-HT3 receptors in the visceral vagal and spinal afferent nerves, chemoreceptor trigger zone, and the vomiting center. They have a rapid onset of action and can be given as a single dose before chemotherapy. Ondansetron and granisetron, in particular,...
171
Drug Elimination by Renal Route: Tubular Secretion01:15

Drug Elimination by Renal Route: Tubular Secretion

Once the process of glomerular filtration is completed, blood carrying unfiltered drug molecules traverses through efferent arterioles and makes its way into the peritubular capillaries in the proximal tubule. A variety of carriers play a pivotal role in actively secreting drugs from these peritubular capillaries into the tubular fluid. The organic anion transporter transfers acidic drugs, against an electrochemical gradient, from the peritubular capillaries into the renal tubule cells and...
2.1K
Chemotherapy-Induced Nausea and Vomiting: Neurokinin-1 Receptor Antagonists01:28

Chemotherapy-Induced Nausea and Vomiting: Neurokinin-1 Receptor Antagonists

Neurokinin 1 (NK1) receptors are distributed across the GI tract, vagal afferents, and key CNS regions including the central vomiting center and chemoreceptor trigger zone (CTZ) Chemotherapy agents stimulate enterochromaffin cells in the gastrointestinal (GI) tract to release large amounts of substance P (SP). SP is a neuropeptide released by specific sensory nerves in response to many different stressors, including those in the GI mucosa affected by chemotherapy.  SP binds and activates...
147
Renal Drug Excretion: Tubular Secretion01:28

Renal Drug Excretion: Tubular Secretion

Active tubular secretion is a robust, energy-demanding process that utilizes carrier systems to transport drugs into renal tubules. The active renal secretion systems include the organic anion transporter (OAT) for weak acids and the organic cation transporter (OCT) for weak bases. Structurally similar drugs can compete for the same transporter, potentially leading to drug accumulation and toxicity. However, this principle can be exploited therapeutically. One example is probenecid (Probalan),...
104
Heart Failure Drugs: Inhibitors of Renin-Angiotensin System01:26

Heart Failure Drugs: Inhibitors of Renin-Angiotensin System

The activation of the sympathetic nervous system and the renin-angiotensin-aldosterone system (RAAS) contributes to cardiac remodeling, and inhibiting the RAAS is a pharmacological target in heart failure management. As a result, neurohumoral modulation is a crucial treatment principle for managing heart failure. This approach involves using medications like ACE inhibitors (ACEIs), angiotensin receptor blockers (ARBs), β-blockers, mineralocorticoid receptor antagonists (MRAs), and neutral...
363