Gemfibrozil, a lipid‐lowering drug, improves hepatorenal damages in a mouse model of aging

Author:

Hakimizadeh Elham12,Tadayon Saeedeh1,Zamanian Mohammad Yasin34ORCID,Soltani Afsaneh5,Giménez‐Llort Lydia6,Hassanipour Mahsa12ORCID,Fatemi Iman7ORCID

Affiliation:

1. Physiology‐Pharmacology Research Center, Research Institute of Basic Medical Sciences Rafsanjan University of Medical Sciences Rafsanjan Iran

2. Department of Physiology and Pharmacology, School of Medicine Rafsanjan University of Medical Sciences Rafsanjan Iran

3. Department of Physiology, School of Medicine Hamadan University of Medical Sciences Hamadan Iran

4. Department of Pharmacology and Toxicology, School of Pharmacy Hamadan University of Medical Sciences Hamadan Iran

5. School of Medicine Iran University of Medical Sciences Tehran Iran

6. Institut de Neurociències & Department of Psychiatry and Forensic Medicine Universitat Autònoma de Barcelona Barcelona Spain

7. Research Center of Tropical and Infectious Diseases Kerman University of Medical Sciences Kerman Iran

Abstract

AbstractGemfibrozil (GFZ) is a medication of the fibrate category with agonistic effects on peroxisome proliferator‐activated receptor‐α (PPAR‐α) and is effective for hypertriglyceridemia and mixed dyslipidemia. This agent also has anti‐inflammatory and antioxidant properties. The current study investigated the effects of GFZ on hepatorenal damages in a D‐galactose (D‐gal)‐induced aging model. We used 28 male mice, which were equally and randomly divided into four groups as follows: normal, D‐gal (150 mg/kg/day; intraperitoneal [i.p.], for 6 weeks), GFZ (100 mg/kg/day GFZ, orally [p.o.] for 6 weeks), and the combined D‐gal + GFZ. Liver and kidney function indices were measured as serum creatinine, blood urine nitrogen, alanine aminotransferase, and aspartate aminotransferase. Oxidative stress in hepatic and renal tissue was evaluated through malondialdehyde, superoxide dismutase, and glutathione peroxidase levels. Finally, the liver and kidney tissues were assessed for histopathological lesions. The results showed that D‐gal‐induced aging leads to abnormalities in liver and kidney function indices. D‐gal also induced significant oxidative stress and histopathological lesions in these organs. GFZ improved function indices and oxidative stress compared to the D‐gal‐treated animals. Histological evaluations of the liver and kidney also confirmed these results. These data provide evidence for the potential therapeutic of GFZ in clinical practice for mitigating the hepatorenal damages of aging.

Funder

Rafsanjan University of Medical Sciences

Publisher

Wiley

Subject

Pharmacology (medical),Pharmacology

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