TY - JOUR
T1 - Gemfibrozil, a lipid-lowering drug, improves hepatorenal damages in a mouse model of aging
AU - Hakimizadeh, Elham
AU - Tadayon, Saeedeh
AU - Zamanian, Mohammad Yasin
AU - Soltani, Afsaneh
AU - Giménez-Llort, Lydia
AU - Hassanipour, Mahsa
AU - Fatemi, Iman
N1 - © 2023 Société Française de Pharmacologie et de Thérapeutique. Published by John Wiley & Sons Ltd.
PY - 2023/6
Y1 - 2023/6
N2 - Gemfibrozil (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.
AB - Gemfibrozil (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.
KW - Aging
KW - Gemfibrozil
KW - Kidney
KW - Liver
KW - Mice
KW - Translational research
KW - Hypolipidemic Agents/pharmacology
KW - Antioxidants/pharmacology
KW - Oxidative Stress
KW - Male
KW - Animals
KW - Gemfibrozil/pharmacology
KW - Disease Models, Animal
UR - https://www.scopus.com/pages/publications/85146307723
UR - https://www.mendeley.com/catalogue/b02994c9-1f4d-3f01-967f-dd3afd3f8684/
U2 - 10.1111/fcp.12865
DO - 10.1111/fcp.12865
M3 - Article
C2 - 36600528
AN - SCOPUS:85146307723
SN - 0767-3981
VL - 37
SP - 599
EP - 605
JO - Fundamental and Clinical Pharmacology
JF - Fundamental and Clinical Pharmacology
IS - 3
ER -