Related Experiment Video

Updated: Apr 23, 2026

Inducing Acute Liver Injury in Rats via Carbon Tetrachloride CCl4 Exposure Through an Orogastric Tube
06:12

Inducing Acute Liver Injury in Rats via Carbon Tetrachloride CCl4 Exposure Through an Orogastric Tube

Published on: April 28, 2020

11.0K

Ochratoxin A induces rat renal carcinogenicity with limited induction of oxidative stress responses

Xiaozhe Qi1, Tao Yu1, Liye Zhu1

  • 1College of Food Science and Nutritional Engineering, China Agricultural University, Beijing 100083, China.

Toxicology and Applied Pharmacology
|September 15, 2014
PubMed

Insights

Ochratoxin A causes kidney damage and potential carcinogenicity in rats, but not through increased oxidative stress. Cell proliferation appears to be the primary mechanism driving these effects, suggesting a new understanding of its toxicity.

Area of Science:

  • Toxicology
  • Molecular Biology
  • Carcinogenesis

Background:

  • Ochratoxin A (OTA) is a known nephrotoxin and renal carcinogen in mammals.
  • The precise mechanisms linking OTA's toxicity, particularly oxidative stress, to renal carcinogenicity remain unclear.

Purpose of the Study:

  • To elucidate the relationship between oxidative stress and OTA-induced renal carcinogenicity.
  • To investigate the molecular changes associated with OTA exposure in rat kidneys and liver.

Main Methods:

  • Rats were administered Ochratoxin A (OTA) at doses of 70 or 210 μg/kg body weight for 4 or 13 weeks.
  • Kidney and liver tissues were analyzed for histological damage, gene expression (clusterin, vimentin, lipocalin 2, p53), and markers of oxidative stress and cell proliferation (PCNA).
  • Kidney Injury Molecule-1 (Kim-1) expression was assessed.

Main Results:

  • Significant kidney damage, including cytoplasmic vacuolization and tubular epithelial karyomegaly, was observed after 13 weeks of OTA exposure.
  • OTA exposure did not significantly alter oxidative stress markers in the liver or kidney.
  • Increased cell proliferation (PCNA) and altered gene expression (decreased p53, increased clusterin, vimentin, lipocalin 2) were observed, particularly in the kidney after 13 weeks.

Conclusions:

  • Ochratoxin A induces substantial kidney damage within 13 weeks, independent of significant changes in oxidative stress levels.
  • Cell proliferation, rather than oxidative stress, is suggested as the primary mode of action for OTA-induced renal carcinogenicity.
  • These findings highlight a potential shift in understanding OTA's toxicological mechanisms.
Keywords:
Cell proliferationNephrotoxicityOchratoxin AOxidative stressRenal carcinogenicity

More Related Videos

The Dimethylnitrosamine Induced Liver Fibrosis Model in the Rat09:27

The Dimethylnitrosamine Induced Liver Fibrosis Model in the Rat

Published on: June 17, 2016

11.8K
Formation of Covalent DNA Adducts by Enzymatically Activated Carcinogens and Drugs In Vitro and Their Determination by 32P-postlabeling09:33

Formation of Covalent DNA Adducts by Enzymatically Activated Carcinogens and Drugs In Vitro and Their Determination by 32P-postlabeling

Published on: March 20, 2018

13.4K

Related Concept Videos

Mutagenicity and Carcinogenicity01:25

Mutagenicity and Carcinogenicity

Mutagenicity and carcinogenicity refer to the ability of drugs to cause genetic defects and induce cancer, respectively. The International Agency for Research on Cancer (IARC) classifies agents into four groups based on their carcinogenic potential. Group 1 agents are known human carcinogens; group 2A agents are probably carcinogenic to humans; group 3 agents lack data to support their role in carcinogenesis; and group 4 includes agents for which data support that they are not likely to be...
2.0K
Physical Properties of Amines01:26

Physical Properties of Amines

Amines with low molecular weight are usually gaseous at room temperature, while those with high molecular weight are liquid or solids in nature. Usually, low molecular weight amines have a rotten fish-like smell. Diamines typically have a pungent smell. For instance, cadaverine and putrescine, depicted in Figure 1, are two molecules responsible for decaying tissue.
3.2K
Toxicity Testing in Animals01:23

Toxicity Testing in Animals

Toxicity tests in animals are grounded on two main assumptions: first, the effects observed in laboratory animals can be extrapolated to humans, especially when adjusted for body surface area; second, high-dose exposure in animals is essential to identify potential human hazards from lower doses. This is based on the quantal dose-response concept, which faces the challenge of extrapolating results from relatively few test animals to much larger human populations. For example, a 0.01% incidence...
198
Drug Toxicity: Dose-Dependent Reactions01:24

Drug Toxicity: Dose-Dependent Reactions

Drug toxicities can be stratified into pharmacological, pathological, or genotoxic based on their mechanisms. The incidence and severity of these toxicities generally increase with the drug's concentration in the body and exposure time.Pharmacological toxicity is evident when the therapeutic effects of drugs overshoot into adverse reactions in a predictable, dose-dependent manner. Central nervous system (CNS) depression from barbiturates is a classic example, with effects escalating from...
228