Hesperidin has a protective effect on paclitaxel-induced testicular toxicity through regulating oxidative stress, apoptosis, inflammation and endoplasmic reticulum stress

Paclitaxel (PTX) is widely used to treat a number of malignancies, although it has toxic side effects. Hesperidin (HES) has a wide range of biological and pharmacological properties, including anti-inflammatory and antiox-idant abilities. This research aims to investigate the role of HES in PTX-induced testicular toxicity. For 5 days, 2 mg/kg/bw i.p. of PTX was administered to induce testicular toxicity. Rats were administered oral dosages of 100 and 200 mg/kg/bw HES for 10 days after PTX injection. The mechanisms of inflammation, apoptosis, endo-plasmic reticulum (ER) stress, and oxidants were investigated using biochemical, genetic, and histological techniques. As a result of PTX administration, decreased antioxidant enzyme (superoxide dismutase, catalase, and glutathione peroxidase) activities and increased malondialdehyde level were regulated, and the severity of oxidative stress was reduced. NF-kappa B, IL-1 beta and TNF-alpha levels, which are among the increased inflammation pa-rameters caused by PTX, decreased with HES administration. Although AKT2 gene expression decreased in PTX administered rats, it was determined that HES administration up-regulated AKT2 mRNA expression. Anti-apoptotic Bcl-2 decreased with PTX administration, and apoptotic Bax and Caspase-3 increased while HES administration reverted these effects towards control level. As a result of toxicity, the increase in ATF6, PERK, IRE1 alpha, GRP78 levels caused prolonged ER stress, and this activity was diminished with HES and tended to regress. While all data were evaluated, Paclitaxel caused damage by increasing inflammation, apoptosis, ER stress and oxidant levels in testicular tissue, and Hesperidin showed a protective effect by correcting the dete-rioration in these levels.

Dergi

REPRODUCTIVE TOXICOLOGY

Yıl

2023

Cilt

118

ISSN

0890-6238

eISSN

1873-1708

DOI

10.1016/j.reprotox.2023.108369

WoS UID

WOS:000967961700001